ГИПОГЛИКЕМИЧЕСКОЕ ЛЕКАРСТВЕННОЕ СРЕДСТВО, СОДЕРЖАЩЕЕ ПРОИЗВОДНЫЕ ПИРАЗИНА, НОВЫЕ ПРОИЗВОДНЫЕ ПИРАЗИНА И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

Описывается гипогликемическое лекарственное средство, содержащее в качестве действующего начала по меньшей мере одно производное пиразина формулы I, в которой R означает атом азота, R1 означает радикал -СО-NR5R6, -СО-N(СН2 -(СНОН)n-СН2ОН)2, где n = 0, -СН2-NR5R6, -СН2-N(СН2 -(СНОН)y-СН2ОН)2, где y = 0, и один из заместителей R3 или R4 означает атом водорода, а другой идентичен R1, R2 означает атом водорода; R5 означает атом водорода или радикал алкил, содержащий 1-6 атомов углерода в прямой или разветвленной цепи, R6 означает радикал -СН2-(СНОН)m -СН2ОН, где m = 1, -алк-О-алк-СН2 ОН, алк-О-алк, -СН(СН2ОН)2, -С(СН2ОН)3, -С(СН3)(СН2ОН)2, алк означает алкил с 1-6 атомами углерода в линейной или разветвленной цепи, или его соли с фармацевтически приемлемой неорганической или органической кислотой. Также описываются производные пиразина формулы I и способы их получения. 4 с. и 2 з.п. ф-лы.

ПРОИЗВОДНЫЕ ПИРИДИН-2-КАРБОКСАМИДА В КАЧЕСТВЕ АНТАГОНИСТОВ mGluR5

Данное изобретение относится к соединениям формулы (I), ! где R1 представляет собой 5- или 6-членное кольцо, соответственно формул (II) или (III): ! ! (II) ! ! ! (III) ! R2 представляет собой Н, С1-С7-алкил, С3-С6-циклоалкил или -(СН2)m-Ra; R3 представляет собой арил или гетероарил, которые возможно замещены: CN, Cl, F, Br, CF3, CHF2, С3-С6-циклоалкилом или представляет собой гетероарил, который возможно замещен С1-С7-алкилом; R4 представляет собой Н, -ОН, Cl, F, Br, CN, -CHF2, CF3, С1-С7-алкил, С3-С6-циклоалкил или -(CH2)m-Re; R5 представляет собой C1-C7-алкил, -(СН2)n-О-Rf, или -(CH2)n-Re; Re представляет собой -ОН; Ra представляет собой -ОН; Re представляет собой С1-С7-алкил; m представляет собой 1-4; n представляет собой 2-6; и к их фармацевтически приемлемым солям. А также, к лекарственному средству, содержащему их, и применению их для изготовления лекарственных средств, пригодных при лечении заболеваний ЦНС. Технический результат: получены и описаны новые соединения, которые могут ...

АГОНИСТЫ ПРОТЕИНТИРОЗИНФОСФАТАЗЫ-1, СОДЕРЖАЩЕЙ ДОМЕН ГОМОЛОГИИ-2 SRC, И СПОСОБЫ ЛЕЧЕНИЯ С ПРИМЕНЕНИЕМ УКАЗАННЫХ АГОНИСТОВ

Изобретение относится к новым соединениям формулы I, которые обладают агонистической активностью в отношении протеинтирозинфосфатазы-1, содержащей домен гомологии-2 Src (SHP-1). В формуле I Rи Rнезависимо представляют собой водород, и Rпредставляет собой,,,,илиRнезависимо представляет собой водород, Rпредставляет собой метил, и Rпредставляет собойилиили Rи Rнезависимо представляют собой водород, и Rпредставляет собой. Изобретение относится также к фармацевтическим композициям, содержащим указанное соединение, к способу повышения экспрессии в клетке протеинтирозинфосфатазы-1, содержащей домен гомологии-2 Src (SHP-1), способу лечения заболевания или патологического состояния, характеризующегося пониженной экспрессией SHP-1, и к применению указанного соединения для получения лекарственного средства для лечения заболевания или патологического состояния, характеризующегося пониженной экспрессией SHP-1. 7 н. и 4 з.п. ф-лы, 6 табл., 23 ил., 2 пр.

НЕПРЕРЫВНЫЕ СПОСОБЫ ГИДРОЛИЗА ЦИАНОПИРИДИНОВ В АДИАБАТИЧЕСКИХ УСЛОВИЯХ

Изобретение относится к непрерывному способу гидролиза цианопиридинов в адиабатических условиях, который заключается в непрерывном объединении двух или более подаваемых потоков с образованием реакционной смеси, содержащей цианопиридин, воду и основание, нагревании ее до температуры, достаточной для того, чтобы инициировать гидролиз цианопиридина. Другой вариант изобретения заключается в объединении первого потока, содержащего цианопиридин, со вторым потоком, содержащим воду и основание, причем по меньшей мере один из потоков нагревают до температуры, обеспечивающей объединенному потоку температуру, достаточную для инициирования гидролиза цианопиридина, пропускания потоков после указанного объединения через зону реакции и проведения реакции гидролиза в практически адиабатических условиях. Такое проведение процесса гидролиза цианопиридинов приводит к повышенным скоростям образования продуктов с высокими выходом и селективностью. 4 с. и 36 з.п. ф-лы, 2 табл.

ПЕСТИЦИДНО АКТИВНЫЕ ГЕТЕРОЦИКЛИЧЕСКИЕ ПРОИЗВОДНЫЕ С СЕРОСОДЕРЖАЩИМИ ЗАМЕСТИТЕЛЯМИ

Изобретение относится к соединению формулы I и к его агрохимически приемлемым солям, где А представляет собой СН или N; X представляет собой S или SO2; R1 представляет собой С1-С4алкил; G1 представляет собой N или СН; X1 представляет собой NR3; где R3 представляет собой С1-С4алкил; R2 представляет собой галоген или C1-С4галогеналкил; R7 представляет собой водород, фтор, циано или C1-С6алкил; и R8 представляет собой фтор, циано, С1-С8алкил или С1-С4алкилоксикарбонил. Изобретение также относится к композиции для контроля насекомых, способу борьбы с насекомыми и способу защиты материала для размножения растений от воздействия насекомых. Технический результат – получены новые соединения и композиция на их основе, которые могут найти применение в сельском хозяйстве в качестве эффективных инсектицидов. 4 н. и 3 з.п. ф-лы, 4 табл., 23 пр.

ЦИКЛИЧЕСКИЕ ИНГИБИТОРЫ ПРОТЕИНТИРОЗИНКИНАЗ

Изобретение относится к N-(2-хлор-6-метилфенил)-2-[[6-[4-(2-гидроксиэтил)-1-пиперазинил]-2-метил-4-пиримидинил]амино]-5-тиазолкарбоксамиду формулы и к его фармацевтически приемлемым солям. Также описана фармацевтическая композиция, ингибирующая протеинтирозинкиназы и содержащая указанное соединение, способ лечения обусловленного протеинтирозинкиназами нарушения, такого как иммунологическое расстройство и онкологическое заболевание, и способ лечения рака. 4 н. и 1 з.п. ф-лы, 25 табл.

ПРОИЗВОДНЫЕ АМИНОКИСЛОТЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ПОДАВЛЕНИЯ МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТИ

Описываются новые соединения формулы I, где В и D независимо друг от друга обозначают водород или Аr-замещенный (C1-С6)-алкил с прямой или разветвленной цепью; R1 - (C1-С6)-алкил с прямой или разветвленной цепью или Аr-замещенный (C1-С6)-алкил с прямой или разветвленной цепью; J обозначает (C1-С6)-алкил с прямой или разветвленной цепью; К обозначает (C1-С6)-алкил с прямой или разветвленной цепью, фенилзамещенный (C1-С6)-алкил с прямой или разветвленной цепью, где фенил может быть замещен галогеном; Х обозначает фенил, замещенный O-(C1-С6)-алкилом; Аr обозначает фенил, или Аr является гетероциклической ароматической группой, выбираемой из группы, включающей 2-пиридил, 3-пиридил, 4-пиридил и имидазолил, причем Аr может быть замещен галогеном, которые могут быть использованы для подавления множественной лекарственной устойчивости. Описывается также способ их получения, фармацевтическая композиция и способ подавления множественной лекарственной устойчивости. 6 c. и 5 з.п. ф-лы, 3 табл.

ОРТОЗАМЕЩЕННЫЕ АЗОТСОДЕРЖАЩИЕ БИСАРИЛЬНЫЕ СОЕДИНЕНИЯ ДЛЯ ПРИМЕНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ КАЛИЕВОГО КАНАЛА, А ТАКЖЕ СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ

Изобретение относится к новым биологически активным орто-замещенным азотсодержащим бисарильным соединениям. Описываются соединения формулы 1, в которой: А1, А2, A3, А4, А5, А6, А7 и А8 независимо друг от друга обозначают азот или СН, причем, по крайней мере, одна или самое большее две из этих групп обозначают азот; R(1) обозначает C(O)OR(9) или COR(11); R(9) и R(11) независимо друг от друга обозначают СхН2х-R(14); x имеет значение 0, 1, 2, 3 или 4, R(14) обозначает алкил с 1, 2, 3, 4, 5 или 6 С-атомами, фенил или изоксазолил, причем фенил и изоксазолил не замещены или замещены 1, 2 или 3 заместителями, выбранными из группы, состоящей из F, Cl, Br, I, CF3, OCF3, алкила с 1, 2, 3 или 4 С-атомами и алкоксигруппы с 1, 2, 3 или 4 С-атомами; R(2) обозначает водород; R(3) обозначает CyH2y-R(16); y имеет значение 0, 1, 2, 3 или 4, причем y не может быть 0, если R(16) обозначает OR(17); R(16) обозначает алкил с 1, 2, 3, 4, 5 или 6 С-атомами, циклоалкил с 3, С-атомами, OR(17), фенил или пиридил, ...

АРИЛАМИДЫ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ИНГИБИРОВАНИЯ TNα-АКТИВИРОВАННОЙ РЕПЛИКАЦИИ РЕТРОВИРУСА

Описываются новые соединения общей формулы I Y-C(=O)-NH-CH(R2)-CH2-C(= O)-Z, в которой R2 представляет 3,4-дизамещенный фенил, в котором каждый заместитель выбран независимо из группы, состоящей из нитро, циано, трифторметила, карбэтокси, карбометокси, карбопропокси, ацетила, карбамоила, ацетокси, карбокси, гидрокси, амино, алкила с 1 - 10 атомами углерода, алкокси с 1 - 10 атомами углерода и галогена; Z представляет алкокси с 1 - 10 атомами углерода, бензилокси, амино или алкиламино с 1 - 10 атомами углерода; Y представляет (i) фенил, незамещенный или замещенный одним или более заместителями, каждый из которых независимо друг от друга выбран из группы, состоящей из нитро, циано, трифторметила, карбэтокси, карбометокси, карбопропокси, ацетила, карбамоила, ацетокси, карбокси, гидрокси, амино, алкила с 1 - 10 атомами углерода, алкокси с 1 - 10 атомами углерода и галогена, или (ii) нафтил. Ариламиды общей формулы I являются ингибиторами фактора некроза опухолевых клеток α и могут использоваться ...

МОНОГИДРАТ 4-[4-({[4-ХЛОР -3(ТРИФТОРМЕТИЛ)ФЕНИЛ]КАРБАМОИЛ}АМИНО)-3-ФТОРФЕНОКСИ]-N-МЕТИЛПИРИДИН-2-КАРБОКСАМИДА

Настоящее изобретение относится к моногидрату 4-[4-({[4-хлор-3-(трифторметил)фенил]карбамоил}амино)-3-фторфенокси]-N-метилпиридии-2-карбоксамида формулы (II) ! ! способу его получения, к применению этого соединения для получения лекарственного средства для лечения гиперпролиферативных заболеваний и к включающей соединение формулы II фармацевтической композиции для лечения гиперпролиферативных заболеваний. Технический результат: получено и описано новое соединение, которое может быть полезно в использовании для контроля за гиперпролиферативными заболеваниями. 5 н. и 4 з.п. ф-лы , 1 пр., 7 табл., 7 ил.

ПОЛИМОРФЫ ДЕЙТЕРИРОВАННОЙ ОМЕГА-ДИФЕНИЛМОЧЕВИНЫ ИЛИ ЕЕ СОЛЕЙ

Изобретение относится к полиморфным формам дейтерированной омега-дифенилмочевины или ее солей, в частности, полиморфные формы 4-(4-{3-[4-хлор-3-(трифторметил)фенил)-уреидо]-фенокси}-2-(N-1',1',1'-тридейтерио-метил)пиколинамида формулы (I)или его соли. Полиморфные формы подходят для получения фармацевтической композиции, применяемой для ингибирования фосфокиназы (такой как raf киназа). 9 н. и 7 з.п. ф-лы, 6 табл., 21 ил., 10 пр.

СИММЕТРИЧНЫЕ И НЕСИММЕТРИЧНЫЕ ПРОИЗВОДНЫЕ ДИФЕНИЛМОЧЕВИНЫ (ВАРИАНТЫ), ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ПОДАВЛЕНИЯ РОСТА ОПУХОЛЕВЫХ КЛЕТОК, ОПОСРЕДОВАННОГО КИНАЗОЙ RAF

Изобретение относится к новым производным дифенилмочевины формулы (I) или их фармацевтически приемлемым солям, которые могут быть использованы при лечении опухолей, опосредованных киназой raf. В общей формуле (I) соединений настоящего изобретения: (I) А означает R3 означает Н, галоген, NO2, С1-10алкил, по выбору замещенный галогеном вплоть до полного замещения; С1-10алкокси, по выбору замещенный галогеном вплоть до полного замещения; R4, R5 и R6 каждый независимо означает Н, галоген, NO2, С1-10 алкил, по выбору замещенный галогеном вплоть до полного замещения; С1-10алкокси, по выбору замещенный галогеном вплоть до полного замещения; и либо один из R4, R5 и R6 по выбору означает -X-Y; либо два соседних R4, R5 и R6 могут быть объединены с основным фенильным кольцом с образованием нафтила или индольной группы, замещенной пиридинильной группой, Х означает -CH2-, -S-, -N(СН3)-, -NHC(O)-, -CH2-S-, -S-CH2, -С(O)-, или -О-. Значения других радикалов указаны в формуле изобретения. Изобретение также ...

ПРОИЗВОДНЫЕ АМИНОМАСЛЯНОЙ, АМИНОПЕНТАНОВОЙ И АМИНОГЕКСАНОВОЙ КИСЛОТ

Изобретение относится к производным аминомасляной, аминопентановой и аминогексановой кислот общей формулы I где R1 - -COOR10; - (CH2)m-CONHOR10, -CONHNHR10, -(CH2)nSR50 или -Y-P (OR51)2; m = 0, 1, 2; n = 0-3; каждый из R2, R3, R4, R5, R6 и R7 независимо является водородом, С1-8 алкилом, С2-8 алкенилом, -OR11, -SR11, -NR12R13, Циклом 1, С1-8 алкилом, замещенным -OR11, -SR11, -NR12R13, -COR14, гуанидино или Циклом 1, или С2-8 алкенилом, замещенным -OR11, -SR11, -NR12R13, -COR14, гуанидино или Циклом 1, или R3 и R4, взятые вместе, представляют С1-8 алкилен, R5 и R6, взятые вместе, представляют С1-8 алкилен, R3 и R6, взятые вместе, представляют С1-8 алкилен, R2 и R3, взятые вместе, представляют С2-8 алкилен, R4 и R5, взятые вместе, представляют С2-8 алкилен или R6 и R7, взятые вместе, представляют С2-8 алкилен, или (1) R8 представляет собой 1) водород, 2) С1-8 алкил, 3) С1-8 алкоксикарбонил, 4) С1-8 алкил, замещенный -OR26, -SR26, -NR27R28 или -COR29, или 5) С1-8 алкоксикарбонил, замещенный ...

ПРОИЗВОДНЫЕ ГИДРОКСИЛАМИНА, ПРИГОДНЫЕ ДЛЯ УСИЛЕНИЯ ОБРАЗОВАНИЯ МОЛЕКУЛЯРНОГО ШАПЕРОНА, И ИХ ПОЛУЧЕНИЕ

Изобретение относится к области медицины и касается способа повышения экспрессии молекулярного шаперона клеткой и/или повышения активности молекулярного шаперона в клетках путем обработки клетки эффективным количеством производного гидроксиламина формулы (I) или (II), а также к новым производным гидроксиламина и фармкомпозициям на их основе. Изобретение позволяет эффективно регулировать клеточные процессы. 13 с. и 132 з.п.ф-лы, 29 ил., 5 табл.

ПРОИЗВОДНЫЕ МОЧЕВИНЫ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Изобретение относится к новым производным мочевины общей формулы (I) и их фармацевтически приемлемым солям, где А представляет собой -СН- или атом азота, R1 представляет собой С3-10 алкил, С3-10циклоалкил, С3-10циклоалкил-С1-10алкил, 6-членный азотсодержащий гетероциклил, 6-членный азотсодержащий гетероциклил-С1-10 алкил, фенил, фенил-С1-10алкил, 5-10-членный гетероарил или 5-10-членный гетероарил-С1-10алкил и др.; R2 представляет собой водород, С1-6алкил, С0-2 алкил-С3-10циклоалкил, С0-2алкил-фенил, С3-10циклоалкил-С0-2алкил или фенил-С0-2алкил; R5 представляет собой C1-6алкил, С3 -10циклоалкил, 6-членный азотсодержащий гетероциклил и др.; L1 представляет собой -S-, -S(О)-, -S(O)2, -С(O)-, -N(Rc)-, -CH2- и др.; L2 представляет собой ковалентную связь, -О-, -С(O)-, -ОС(O)-, -N(Rc)- и др.; W представляет собой О или S; Z представляет собой -C(O)ORd; Rc, Rd и Re представляют собой водород или алкил; Rb представляет собой -ORe, -NO2, галоген, -CN, -CF3, C1-6алкил; р представляет собой целое ...

ЦИКЛИЧЕСКИЕ ИНГИБИТОРЫ ПРОТЕИНТИРОЗИНКИНАЗ

Настоящее изобретение относится к способу лечения хронической миелогенной лейкемии, стромальной опухоли желудочно-кишечного тракта, герминогенной опухоли, мелкоклеточного рака легких, меланомы, рака поджелудочной железы, рака простаты, хронической миелогенной лейкемии, резистентной к STI-571, заключающемуся в пероральном введении пациенту от 1 до 4 раз в день от 0,1 до 100 мг/кг веса соединения формулы (IV) или его фармацевтически приемлемой соли ! ! 8 н. и 2 з.п. ф-лы, 2 табл.

ПРОИЗВОДНЫЕ АМИДА, СПОСОБ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Изобретение относится к производным амида формулы I где R3 представляет собой (1-6С)алкил или галоген; m равно 0, 1, 2 или 3; R1 представляет собой гидрокси, галоген, трифторметил, нитро, амино, (1-6С)алкил, (2-6С)алкенил, (2-6С)алкинил, (1-6С)алкокси, (1-6С)алкиламино, ди-[(1-6С)алкил] амино, амино-(2-6С)алкиламино, (1-6С)алкиламино-(2-6С)алкиламино и т.д. или R1 представляет собой арил, арил-(1-6С)алкил, гетероарил, гетероарил-(1-6С)алкил, гетероарилокси, гетероарил-(1-6С)алкокси, гетероциклил, гетероциклил-(1-6С)алкил или гетероциклилокси, р равно 0, 1 или 2; R2 представляет собой гидрокси, галоген, трифторметил, (1-6С)алкил или (1-6С)алкокси; R4 представляет собой амино, (1-6С)алкиламино, ди-[(1-6С)алкил] амино, амино-(1-6С)алкил, (1-6С)алкиламино-(1-6С)алкил и т.д. или R4 представляет собой гетероарил, гетероарил-(1-6С)алкил, гетероарилокси, гетероарил-(1-6С)алкокси, гетероциклил и т.д., q равно 0, 1, 2, 3 или 4 и Q2 представляет собой гетероарил, гетероарилокси или гетероарил-(1-6С ...

ИНГИБИТОРЫ КАСПАЗ И ИХ ПРИМЕНЕНИЕ

Настоящее изобретение относится к соединению формулы I: ! ! в которой: R1 представляет R6C(O)-, HC(O)-, ! R6SO2-, R6OC(O)-, (R6)2NC(O)-, R6-, ! (R6)2NC(O)C(O)-; R2 представляет атом водорода, -CF3 или R8; R3 представляет атом водорода или (С1-С4)алифатическую группу-; R4 представляет -СООН; R5 представляет -CH2F или -СН2О-2,3,5,6-тетрафторфенил; R6 представляет (С1-С12)алифатическую или (С3-С10)циклоалифатическую группу, (С6-С10)арил-, (С3-С10)гетероциклил-; и где R6 замещен до 6 заместителями, независимо выбранными из R; R представляет атом галогена, -OR7 и -R7; R7 представляет (С1-С6)алифатической группы-, (С3-С10)циклоалифатическую групп; R8 представляет (С1-С12)алифатическую- или (С3-С10)циклоалифатическую группу; к фармацевтической композиции, обладающей каспаз-ингибирующей активностью, на основе соединений формулы I, к способам лечения, а также к способам ингибирования опосредуемой каспазой функции и способу снижения продукции IGIF или IFN-β. Кроме того, изобретение относится к способу ...

ЦИКЛОАЛКИЛЬНЫЕ ПРОИЗВОДНЫЕ 3-ГИДРОКСИ-4-ПИРИДИНОНОВ

Настоящее изобретение относится к циклоалкильному производному 3-гидрокси-4-пиридинона общей формулы , где R1 является X при условии, что R2 является Y; или R1 является Т при условии, что R2 является W; или R1 является X при условии, что R2R5N, вместе взятые, образуют гетероциклическое кольцо, выбранное из морфолинила или пиперазинила, где морфолинильная или пиперазинильная группа является либо незамещенной, либо замещенной одной-тремя С1-С6алкильными группами; X является С3-С6циклоалкилом; Y выбирают из группы, состоящей из С3-С6циклоалкила, С1-С6алкила и С1-С6алкила, монозамещенного С3-С6циклоалкилом; Т означает С1-С6 алкил; W означает С3-С6циклоалкил; R3 означает водород; R4 выбирают из группы, состоящей из водорода и С1-С6алкила и; R5 выбирают из группы, состоящей из водорода и С1-С6алкила, и к его способу получения. Также изобретение относится к фармацевтической композиции на основе этих соединений и применению этих соединений в производстве лекарственного препарата. Технический результат ...

ПИРИДИНКАРБОКСАМИДИНЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Изобретение относится к новым пиридинкарбоксамидинам формулы (I) или их таутомерным формам, где присоединение к пиридину осуществляется в положении 2, 3 или 4; R1 обозначает водород; Q обозначает С1 -С9-двухвалентный насыщенный углеводородный радикал; Х обозначает метилен или кислород; R обозначает водород, галоген, нитро, метилендиокси, алкил или алкокси, содержащие от 1 до 4 атомов углерода, или их фармацевтически приемлемым нетоксичным смолям и N-оксидам. Соединения формулы (I) ингибируют нежелательную пролиферацию клеток, например клеток кожи и раковых клеток, и могут найти применение в медицине. 3 с. и 3 з.п.ф-лы, 3 табл.

ПРОИЗВОДНЫЕ СОЛЕЙ ПИРИДИНИЯ, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ НА ИХ ОСНОВЕ И СПОСОБЫ ЛЕЧЕНИЯ

Изобретение относится к новым солям пиридиния общей формулы (I) или их фармацевтически приемлемым солям, где R1 представляет -R4 - R5 или -N(R7)N(R7)R9, R4 выбирают из группы -N(R7)R6О-, N(R7)R6N(R7), -OR6O-, -ОR6N(R7)-, где R6 - алкил, R5 выбирают из группы: алкил, арил, включая гетероарил, -COR7, -SO2R7 и -COR10, где R7 - H, алкил или арил, включая гетероарил, R2 - F, Cl, Br, J, алкил, арил, включая гетероарил, формил, ацил, С(O)NR7R10 или С(O)ОR7, m = 0, 1 или 2, R3 выбирают из группы, включающей R7, OR7, N(R7)(R10) и CH(R7)C(O)R8, R8 представляет R7, OR7 и NR7R10, R9 - водород, алкил, арил, включая гетероарил, -C(O)R10, -SO2R10, -C(S)NHR10, -C(NH)NH(R10), -С(O)NHR10, R10 - H, алкил, или арил, включая гетероарил, и в каждом случае он необязательно отличается от R7, Х представляет ион гологена при условии, что 1) если две алкильные группы находятся у одного углерода или азота, они необязательно связаны вместе с образованием циклической структуры, и 2) азот гетероарильного кольца R10, ...

БИСАМИДНЫЕ ПРОИЗВОДНЫЕ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНСЕКТИЦИДНЫХ СОЕДИНЕНИЙ

Изобретение относится к соединению формулы (I), в которой A, A, Aи Aнезависимо друг от друга обозначают C-X; каждый X независимо обозначает водород; Rи Rнезависимо друг от друга обозначают водород; Gи Gобозначают кислород; Qобозначает фенил или фенил, содержащий от 1 до 2 заместителей R, которые могут быть одинаковыми или разными, или Qобозначает пиридил, содержащий 1 заместитель R; Qобозначает фенил или фенил, содержащий от 1 до 2 заместителей R, которые могут быть одинаковыми или разными; каждый Rнезависимо обозначает галоген, цианогруппу; каждый Rнезависимо обозначает галоген, C-C-алкил, C-C-галогеналкил; Rобозначает C-C-перфторалкил; Yи Yнезависимо друг от друга обозначают галоген, C-C-алкил; и Yи Yобозначают водород; или его соль или N-оксид. Также изобретение относится к соединению формулы (II′). Соединения формулы (I) используют в инсектицидных, акарицидных, нематоцидных или моллюскоцидных композициях и способах для борьбы с насекомыми, клещами, нематодами или моллюсками и их уничтожения ...

НОВОЕ ПРОИЗВОДНОЕ АНТРАНИЛОВОЙ КИСЛОТЫ ИЛИ ЕГО СОЛЬ

Изобретение относится к новым производным антраниловой кислоты, обладающим ингибирующей активностью в отношении продуцирования металлопротеазы 13 матрикса формулы 1 ! , ! где R1 представляет собой атом водорода или карбоксизащитную группу, выбранную из C1-3алкила; R2 представляет собой фенил, С3-6циклоалкил, насыщенную или ненасыщенную 5-6-членную гетероциклическую группу, содержащую 1-3 гетероатома, выбранных из N, О, S, которая может быть конденсирована с фенилом, которые могут быть необязательно замещены C1-6алкилом, C1-6алкокси, ацетилом, ацетокси, галогеном, галогенС1-6алкилом, нитрогруппой, гидроксильной группой, CN, аминогруппой, фенилом, насыщенной или ненасыщенной 5-6-членной гетероциклической группой, содержащей 1-4 гетероатома, выбранных из N, О, S, которая может быть дизамещена C1-6алкилом; R3 представляет собой фенил, С3-6циклоалкил, С5циклоалкенил, насыщенную или ненасыщенную 5-6-членную гетероциклическую группу, содержащую 1-3 гетероатома, выбранных из N, О, S, которая может ...

АМИДЫ СУЛЬФАМИДО- И СУЛЬФАМИДОКАРБОНИЛПИРИДИН-2-КАРБОНОВЫХ КИСЛОТ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Амиды сульфамидo- и сульфамидокарбонилпиридин-2-карбоновых кислот формулы I, где А = R3, а B = -Х-NR6R7 или B = R3, а А = -Х-NR6R7; X - простая связь или -СО-; R1, R2, R3 - одинаковые или различный и означают водород, незамещенный С1-С4-алкил, -(С1-С6)-алкокси, фтор, бром; R4, R5 - независимо друг от друга - Н, С1-С8 алкил, С6-С10-арил, С7-С11ар-С1-С6-алкил, С1-С8-алкилокси, возможно однократно замещенные гидрокси, карбокси, С1-С6-алкилоксикарбонилом, С1-С6-алкокси; R6-Н, С1-С6-алкил, одновалентный физиологически приемлемый катион - Na+, K+; R7 - остаток формулы II (за исключением SO2H). Y-[C-U]r-D-W, где Y-SO2; С-связь, С1-С8-алифатический алкандиил; U-связь, -O-; D-связь; W-Н, тиенил, С6-С10-арил, причем U означает -O- в том случае, если С не означает связь, а W предпочтительно замещено, например, группой -O-(CH2)xCfH(2f+1-q)Fq; f = 1-8; q = 0,1-(2f+1), r = 1,2; X = 0-8. Используют в качестве фармацевтической композиции с антифиброзной активностью. Соединение I, где Х - простая связь, ...

4-АМИНОПИКОЛИНАТЫ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ГЕРБИЦИДОВ

Описываются соединения 4-аминопиколиновой кислоты формулы I: где Х обозначает Н, галоген, C1-С6 алкокси, C1-C6 алкилтио, нитро, трифторметил; Y обозначает галоген, C1-С6 алкокси, трифторметил, фенокси, Z обозначает галоген, C1-С6 алкокси; W обозначает -NO2, -Т3, -NR1R2, где R1 и R2 независимо представляют Н, C1-С6 алкил, С3-С6 алкенил, гидрокси, C1 -C6 алкокси, C1-С6 ацил или R1 и R2, взятые вместе с N, представляют пирролидин или пиррол; и их сельскохозяйственно-приемлемые соли, сложные C1-C12 эфиры или амиды. Описывается гербицидная композиция и способ борьбы с нежелательной растительностью. Технический результат заключается в подавлении широкого спектра сорняков в посевах риса, пшеницы, кукурузы. 3 с. и 7 з.п. ф-лы, 10 табл.

НОВЫЙ АГОНИСТ БЕТА РЕЦЕПТОРА ТИРЕОИДНОГО ГОРМОНА

Изобретение относится к новому соединению формулы [I] или к его фармакологически приемлемой соли, где A представляет собой необязательно замещенный алкил, где заместитель представляет собой одинаковые или различные 1-3 группы, выбранные из арила, необязательно замещенного 1-3 группами, выбранными из алкила, галогена, алкокси и алканоила; циклоалкила, необязательно замещенного 1-3 группами, выбранными из алкила и галогена; гидрокси; алкокси; галогена; аминогруппы и оксо; необязательно замещенную карбоциклическую группу, выбранную из моно- и бициклической группы, где конденсированы ароматическое кольцо и циклоалкил, необязательно замещенный арил, необязательно замещенную 5- или 6-членную моноциклическую гетероциклическую группу, полностью насыщенную, каждая из которых содержит 1 гетероатом, выбранный из азота и кислорода, где заместитель необязательно замещенного арила, необязательно замещенной карбоциклической группы и необязательно замещенной гетероциклической группы для A представляет ...

ПРОИЗВОДНЫЕ БЕНЗАМИДОВ И ГЕТЕРОАРЕНОВ

Настоящее изобретение относится к новым соединениям формулы I: ! , ! а также к их фармацевтически приемлемым солям, обладающим ингибирующей активностью в отношении белка-переносчика холестерилового эфира (БПХЭ), к способу их получения, фармацевтической композиции на их основе и к их применению для приготовления лекарственных средств. Значения заместителей R1, R2, R4, R5, а также А, В, D и n указаны в формуле изобретения. 4 н. и 10 з.п. ф-лы.

АМИДОАЛКАНОЛНИТРАТЫ И СПОСОБ ИХ ПОЛУЧЕНИЯ

Изобретение относится к физиологически активным соединениям и касается амидоалканолнитратов, а также способа их получения. Описываются новые соединения - амидоалканолнитраты общей формулы (1) ANH(CH2)nONO2, где А - остаток уксусной кислоты, замещенной никотиноиламиногруппой, n = 2; или остаток пропионовой кислоты, замещенной никотиноиламиногруппой, n = 2; или остаток масляной кислоты, замещенной никотиноиламиногруппой, n = 3; или остаток капроновой кислоты, замещенной никотиноиламиногруппой, n = 2; или остаток уксусной кислоты, замещенной изоникотиноиламиногруппой; n = 2; или остаток пропионовой кислоты, замещенной изоникотиноиламиногруппой, n = 2; или остаток масляной кислоты, замещенной изоникотиноиламиногруппой, n = 2; или остаток капроновой кислоты, замещенной изоникотиноиламиногруппой, n = 2; или А - группа -О2NОСН2 СН2 NHC(CH2)3NHC(O)PyC(O)NH(CH2)3C(O), n = 2, где Ру - пиридин, замещенный в положениях 2 и 6, соединения обладают коронародилатоторным эффектом и обладают меньшей токсичностью ...

СЛОЖНЫЕ ЭФИРЫ АЦИЛСУЛЬФОНАМИДО- И СУЛЬФОНАМИДОПИРИДИН-2-КАРБОНОВОЙ КИСЛОТЫ, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

Изобретение относится к сложным эфирам ацилсульфонамидо- и сульфонамидопиридин-2 карбоновой кислоты, к содержащим их фармацевтическим композициям и способу получения композиций. Сущность изобретения: сложные эфиры ацилсульфоамидо- и сульфонамидопиридин-2 карбоновой кислоты общей формулы, приведенной в описании, где X обозначает простую связь или C(O)-, R4- линейный или разветвленный алифатический C1C8-алкил; R6 обозначает радикал формулы II, за исключением -SO2H, -SO2-C-V-W (II), где C-связь, линейный или разветвленный C2-C8-алкандиил; V обозначает связь или водород; W обозначает C6-C12-арил, при условии, что исключаются следующие соединения: метил-5-{ ((фенилсульфонил) амино) карбонил} пиридин-2-карбоксилат, метил-5-{((4-метоксифенилсульфонил)амино) карбонил} - пиридин-2-карбоксилат. Соединения формулы I ингибируют ферменты пролин- и лизингидроксилазу, вызывают очень селективное подавление биосинтеза коллагена. 3 с. и 1 з.п. ф-лы, 1 табл.

АЛКИНИЛПИРИДИНОВЫЙ ИНГИБИТОР ПРОЛИЛГИДРОКСИЛАЗЫ, СПОСОБ ЕГО ПОЛУЧЕНИЯ И МЕДИЦИНСКОЕ ПРИМЕНЕНИЕ

Настоящее изобретение относится к области фармацевтической химии. В частности, настоящее изобретение относится к классу алкинилпиридиновых ингибиторов (I) пролилгидроксилазы. Эксперимент показывает, что такое соединение обладает хорошей активностью ингибирования пролилгидроксилазы и может усилить генерацию и секрецию эритропоэтина на клеточных или животных моделях, и, таким образом, может способствовать генерации эритроцитов и может быть использовано для лечения или профилактики анемии, такой как анемия при хроническом заболевании почек, и ишемических заболеваний, таких как ишемические инсульты, ишемия миокарда и другие соответствующие заболевания. Настоящее изобретение также раскрывает способ получения такого соединения. 8 н. и 8 з.п. ф-лы, 2 ил., 4 табл., 69 пр.

ЗАМЕЩЕННЫЕ ПИПЕРАЗИНЫ, (1,4)-ДИАЗЕПИНЫ И 2,5-ДИАЗАБИЦИКЛО(2,2,1)ГЕПТАНЫ В КАЧЕСТВЕ Н1-И/ИЛИ Н3-АНТАГОНИСТОВ ГИСТАМИНА ИЛИ ОБРАТНЫХ Н3-АНТАГОНИСТОВ ГИСТАМИНА

... 1. Соединение формулы (I) где R1 представляет собой водород, -С1-6алкил, -С1-6алкокси, -С3-8циклоалкил, -С1-6алкил-С3-8циклоалкил, арил, гетероциклил, гетероарил, -С1-6алкил-арил, -С1-6 алкил-гетероарил, -С1-6алкил-гетероциклил, -арил-арил, -арил-гетероарил, -арил-гетероциклил, -гетероарил-арил, -гетероарил-гетероарил, -гетероарил-гетероциклил, -гетероциклил-арил, -гетероциклил-гетероарил, -гетероциклил-гетероциклил, где R1 может быть возможно замещен одним или более чем одним заместителем, которые могут быть одинаковыми или разными и которые выбраны из группы, состоящей из галогена, гидрокси, COOR15, циано, -С1-6алкил-циано, нитро, оксо, трифторметила, трифторметокси, фторметокси, дифторметокси, С1-6алкила (возможно замещенного группой COOR15), С2-6алкенила (возможно замещенного группой COOR15), С2-6алкинила (возможно замещенного группой COOR15), С1-6алкокси (возможно замещенного группой COOR15), пентафторэтила, C1-6алкокси, С2-6алкенокси, арила, арилС1-6алкила, -СО-арила (возможно замещенного ...

АЦИЛИРОВАННЫЕ 6, 7, 8, 9 - ТЕТРАГИДО - 5H - БЕНЗОЦИКЛОГЕПТЕНИЛАМИНЫ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ФАРМАЦЕВТИЧЕСКИХ ПРЕПАРАТОВ

... 1. Ацилированный 6,7,8,9-тетрагидро-5Н-бензоциклогептениламин общей формулы (I) в любых стереоизомерных формах или их смеси в любых соотношениях или фармацевтически приемлемая соль указанного соединения где R1 и R4 независимо друг от друга выбирают из группы, включающей Н, незамещенный и, по крайней мере, монозамещенный С1-С10-алкил, С2-С10-алкенил и С2-С10-алкинил, заместители которых выбирают из группы, включающей F, OH, С1-С8-алкокси, (С1-С8 -алкил)меркапто, CN, COOR6, CONR7R8; незамещенный и, по крайней мере, монозамещенный фенил и гетероарил, заместители которых выбирают из группы, включающей галогены, псевдогалогены, С1-С3-алкил, С1-С3-алкокси и CF3; незамещенный и, по крайней мере, монозамещенный фенил и гетероарил, заместители которых выбирают из группы, включающей галогены, псевдогалогены, С1-С3-алкил, С1-С3-алкокси и CF3; R9CO, CONR10R11, COOR12, CF3, галогены, псевдогалогены, NR13R14, OR15, S(O)mR16, SO2NR17R18 и NO2 ; R2 и R3 независимо друг от друга выбирают из группы, включающей ...

СРЕДСТВА НА ОСНОВЕ ГЕТЕРОЦИКЛИЧЕСКОГО ДИАМИДА ДЛЯ СРЕДСТВА НА ОСНОВЕ ГЕТЕРОЦИКЛИЧЕСКОГО ДИАМИДА ДЛЯ БОРЬБЫ С БЕСПОЗВОНОЧНЫМИ ВРЕДИТЕЛЯМИ БОРЬБЫ С БЕСПОЗВОНОЧНЫМИ ВРЕДИТЕЛЯМИ

... 1. Соединение формулы I, его N-оксид или приемлемая соль где A и B обозначают независимо O или S; каждый J обозначает независимо фенильное кольцо, нафтильную кольцевую систему, 5- или 6-членное гетероароматическое кольцо или ароматическую 8-, 9- или 10-членную конденсированную гетеробициклическую кольцевую систему, где каждое кольцо или кольцевая система необязательно замещены 1-4 R5; K обозначает, вместе с двумя соседними связующими атомами углерода, 5- или 6-членное гетероароматическое кольцо, необязательно замещенное 1-3 R4; n равно 1-3; R1 обозначает H; или C1-C6алкил, C2-C6алкенил, C2 -C6алкинил или C3-C6циклоалкил, каждый из которых необязательно замещен одним или несколькими заместителями, выбранными из группы, включающей галоген, CN, NO2, гидрокси, C1 -C4алкокси, C1-C4алкилтио, C1-C4алкилсульфинил, C1-C4алкилсульфонил, C2-C4алкоксикарбонил, C1-C4алкиламино, C2-C8диалкиламино и C3-C6циклоалкиламино, или R1 обозначает C2-C6 алкилкарбонил, C2-C6алкоксикарбонил, C2- C6алкиламинокарбонил ...

ПРОИЗВОДНЫЕ 2-АМИНОКАРБОНИЛПИРИДИНА

... 1. Соединение формулы I ! , ! где R1 представляет собой галоген или имидазолильное, пиразолильное, 1,2,3-триазолильное или 1,2,4-триазолильное кольцо, которое может быть замещено метильной группой, или также R1 представляет собой фенил, необязательно замещенный от 1 до 3 раз заместителями, каждый из которых независимо выбирают из группы, включающей галоген, метил, метоксигруппу, трифторметил и трифторметоксигруппу; ! W представляет собой связь и R2 представляет собой водород, галоген, алкил, гидроксиалкил, алкоксиалкил, циклоалкил, арил или гетероарил; или ! W представляет собой -О- или -S- и R2 представляет собой алкил, циклоалкил, арил или гетероциклил; или ! W представляет собой -NR3-, R2 представляет собой алкил, гидроксиалкил или алкоксиалкил и R3 представляет собой водород или алкил; или ! W представляет собой -С≡С- и R2 представляет собой гидроксиалкил или алкоксиалкил; или ! W представляет собой -NR3- и R2 и R3 образуют вместе с атомом азота, к которому они присоединены, гетероциклическое ...

СПОСОБ ПОЛУЧЕНИЯ ВИТАМИНОВ СЕРИИ K

Настоящее изобретение относится к способу получения витаминов серии K, включающему окисление исходного 2-метилнафталина соединениями шестивалентного хрома в кислой среде при нагревании с получением 2-метил-1,4-нафтохинона (менадиона) на первой стадии, взаимодействие менадиона с водным раствором бисульфита натрия в двухфазной системе, состоящей из водной фазы и органического растворителя с кристаллизацией менадиона натрия бисульфита (MSB) на второй стадии, использование маточного раствора после отделения MSB либо раствора без выделения кристаллов MSB в реакции с никотинамидом при подкислении с получением MNB на третьей стадии. При этом полученный на третьей стадии MNB репульпируют в воде и органическом растворителе с расщеплением на MSB и никотинамид под действием щелочных агентов при значении рН в интервале 4,5-7,0, затем добавляют водорастворимые соединения алюминия (в весовом соотношении сухой MNB и AlOкак 1:0,01-1) при поддержании рН раствора 4,0-5,0 с последующим поднятием рН до 5,0 ...

ГИДРОКСИЭТИЛАМИНОСУЛЬФОНАМИДЫ, ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ИНГИБИРОВАНИЯ РЕТРОВИРУСНЫХ ПРОТЕАЗ, СПОСОБ ЛЕЧЕНИЯ РЕТРОВИРУСНЫХ ИНФЕКЦИЙ, СПОСОБ ЛЕЧЕНИЯ СПИДА

В изобретении предлагаются гидроксиэтиламиносульфонамидные соединения α- и b-аминокислот, эффективные в качестве ингибиторов ретровирусных протеаз и, в частности, в качестве ингибиторов протеазы ВИЧ, а также фармацевтические композиции.

ПРОИЗВОДНЫЕ 6-АМИНО-5,6,7,8-ТЕТРАГИДРОНАФТАЛЕН-2-ИЛА ИЛИ 3-АМИНОХРОМАН-7-ИЛА В КАЧЕСТВЕ МОДУЛЯТОРОВ TAAR

ГЕТЕРОЦИКЛИЧЕСКИЕ ПРОИЗВОДНЫЕ КАРБОНОВОЙ КИСЛОТЫ И ИХ СОЛИ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ С АНТИФИБРОТИЧЕСКОЙ ИЛИ ТОРМОЗЯЩЕЙ ПРОЛИЛГИДРОКСИЛАЗУ ИЛИ БИОСИНТЕЗ КОЛЛАГЕНА АКТИВНОСТЬЮ

Гетероциклические производные карбоновой кислоты и их соли могут представлять собой активное вещество фармацевтической композиции с антифибротической или тормозящей пролилгидроксилазу или биосинтез коллагена активностью.

ПРОИЗВОДНЫЕ УКСУСНОЙ КИСЛОТЫ

Производные уксусной кислоты формулы I, где L, M, Q и Т имеют значения, указанные в описании, могут находить применение для лечения или профилактики заболеваний, обусловленных связыванием адгезивных протеинов с тромбоцитами, а также агрегацией тромбоцитов и адгезией клетка-клетка. Их получают путем отщепления защитных групп в соответствующих защищенных соединения или переводом циановой группы в амидиновую группу в соответствующих нитрилах.

НОВЫЕ ФЕНИЛАМИДНЫЕ ИЛИ ПИРИДИЛАМИДНЫЕ ПРОИЗВОДНЫЕ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ АГОНИСТОВ GPBARI

... 1. Соединения формулы:гдеАпредставляет собой CRили N;Апредставляет собой CRили N;Rи Rнезависимо друг от друга выбраны из группы, состоящей из водорода, С-алкила, галогена, цианогруппы и С-алкоксигруппы;Rи Rнезависимо друг от друга выбраны из группы, состоящей из водорода, С-алкила, галогена, цианогруппы, C-алкоксигруппы, аминогруппы и С-алкилсульфанила;Rвыбран из группы, состоящей из водорода, С-алкила, галогена, С-алкоксигруппы, цианогруппы, С-циклоалкила, N-гетероциклила, пятичленного гетероарила и фенила;Rвыбран из группы, состоящей из метила, этила, изопропила, дифторметила, трифторметила, циклопропила и оксетанила; илиRи Rвместе представляют собой -X-(CRR)- и образуют часть кольца; гдеХ выбран из группы, состоящей из -CRR-, О, S, С=O;Rи Rнезависимо друг от друга выбраны из водорода или С-алкила;Rи Rнезависимо друг от друга выбраны из группы, состоящей из водорода, С-алкила, C-алкоксикарбонила, незамещенного гетероциклила и гетероциклила, замещенного одной или двумя группами, выбранными ...

ПРОИЗВОДНЫЕ АРИЛАМИДОВ В КАЧЕСТВЕ БЛОКАТОРОВ TTX-S

... 1. Соединение следующей формулы (I)где Rнезависимо выбирают из группы, состоящей из -CF, -CHF, -OCF, -OCHF, -OCHCHF, -OCHCF, -OCFCHF, -OCFCF, -OCHCHCF, -ОСН(СН)CF, -ОСНС(СН)F, -OCHCFCHF, -OCHCFCF, OCHCHOCHCF, -NHCHCF, -SCF, -SCHCF, -CHCF, -CHCHCF, -CHOCHCFи -OCHCHOCF;Rнезависимо выбирают из группы, состоящей из:(1) водорода, (2) галогена, (3) гидроксила, (4) -O-Cалкила, где алкил является незамещенным или замещен одним или более заместителями, независимо выбранными из R, (5) -O-Сциклоалкила, где циклоалкил является незамещенным или замещен одним или более заместителями, независимо выбранными из R, (6) -O-Салкенила, где алкенил является незамещенным или замещен одним или более заместителями, независимо выбранными из R, (7) -O-фенила или -O-нафтила, где фенил или нафтил является незамещенным или замещен одним или более заместителями, независимо выбранными из R, (8) -O-гетероциклической группы, где гетероциклическая группа является незамещенной или замещена одним или более заместителями, независимо ...

АЦИЛИРОВАННЫЕ ИНДАНИЛАМИНЫ И ИХ ИСПОЛЬЗОВАНИЕ В КАЧЕСТВЕ ФАРМАЦЕВТИЧЕСКИХ СРЕДСТВ

... 1. Ацилированный инданиламин общей формулы (I) в любой из его стереоизомерных форм или их смесей в любом соотношении или его фармацевтически приемлемая соль где R1 и R4, независимо выбраны из группы, состоящей из Н; незамещенных и, по меньшей мере, монозамещенных С1-С10-алкила, С2-С10-алкенила и С2-С10-алкинила, заместители которых выбраны из группы, состоящей из F, OH, С1-С8-алкокси, (С1-С8-алкил)меркапто, CN, COOR6, CONR7R8 и незамещенных и, по меньшей мере, монозамещенных фенила и гетероарила, заместители которых выбраны из группы, состоящей из галогенов, псевдогалогенов, С1-С3-алкила, С1-С3-алкокси и CF3; R9CO; CONR10R11; COOR12; CF3; галогенов; псевдогалогенов; NR13R14; OR15; S(O)mR16; SO2NR17R18 и NO2; R2 и R3 независимо выбраны из группы, состоящей из Н; галогенов; псевдогалогенов, незамещенного и, по меньшей мере, монозамещенного С1-С10-алкила, заместители которого выбраны из группы, состоящей из ОН, фенила и гетероарила; ОН; C1-C10-алкокси; фенокси; S(O)m R19; CF3; CN; NO2; (С1 ...

Способ получения N-никотиноил-гамма-аминомасляной кислоты или ее эфиров

CПOCOБ ПOЛУЧEHИЯ ДИAMИДOB N, N-БИC (AЛKOKCИAЛKИЛ)-ПИPИДИH-2,4-ДИKAPБOHOBOЙ KИCЛOTЫ

Способ получения диамида 2,6-пиридинкарбоновой кислоты

Способ извлечения меди из водных растворов, содержащих ион хлора

Изобретение относится к способам извлечения меди экстракцией из растворов, полученных выщелачиванием медьсодержащих сульфидных руд растворами хлорида трехвалентного железа. Цель изобретения - упрочнение процесса. В качествеэкстраген- та в предложенном способе извлечения меди из указанных растворов используют замещенный пиридин, содержащий группу (СОХ)п. где X - группа OR, R, - разветвленная цепьалкильной группы, и обе группы R. содержат вместе 16-32 атома углерода. 5 з. п. ф-лы, 2 табл. лачивания представляет собой труднопреодолимую задачу. Изобретением является способ извлечения ценных металлов из водных растворов , содержащих галоидные ионы, с помощью экстрагентов металлов, некоторые свойства которых удовлетворяют строгим требованиям к экстрагенту для применения в системе. Цель изобретения - упрощение способа . Согласно изобретению способ экстракции извлечения меди из водных растворов, содержащих ион хлорида, включает в себя обработку растворов экстрагирующим агентом и повторное экстрагирование ...

Способ получения азотнокислого эфира N-/2-оксиэтил/ никотинамида или его солей

Способ получения производных -метил-3,4 диоксифенилаланина или их солей

Способ получения органических соединений

Способ получения амидов пиридинкарбоновой кислоты

Способ получения эфира азотной кислоты N-/2-оксиэтил/-никотинамида или его солей

SULFONAMIDDERIVATE ALS ASPARTYLPROTEASE-INHIBITOREN

ANILID-DERIVATE ALS FUNGIZIDE

ANILID-DERIVATE ALS FUNGIZIDE

Hydroxyethylaminosulfonamide verwendbar als Inhibitoren retroviraler Proteasen

VERBINDUNGEN ALS PDE IV UND TNF INHIBITOREN

Pyrimidinderivate.

VERFAHREN ZUR HERSTELLUNG VON SUBSTITUIERTEN 2-CHLORPYRIDINEN

VERFAHREN ZUR HERSTELLUNG VON SUBSTITUIERTEN NICOTINAMID 1-OXYD N- UND SEINEN SALZEN

"BIS-(CARBOXAMID)-DERIVATE"

PHARMAZEUTISCH WIRKSAME VERBINDUNGEN UND METHODEN ZU IHRER ANWENDUNG

VERFAHREN ZUR HERSTELLUNG VON IMIDATEN.

PYRIDINYLPYRIMIDIN-DERIVATE, VERFAHREN ZU DEREN HERSTELLUNG UND DIESE ALS WIRKSAMEN STOFF ENTHALTENDE PFLANZENKRANKHEITEN-SCHUTZMITTEL.

HEMMUNG DER RAF-KINASE UNTER VERWENDUNG VON SYMMETRISCH UND UNSYMMETRISCH SUBSTITUIERTEN HARNSTOFFEN

VERFAHREN ZUR HERSTELLUNG EINER AMIDVERBINDUNG

Verfahren zum galvanischen Niederschlagen von Nickel

KRISTALLINE HYDRATE VON ANILID-DERIVATEN ALS FUNIGIZIDE UND INSEKTIZIDE

PHENOL ESTERS

PHENYL- UND PYRIDINYL-DERIVATE VERWENDBAR ALS NEUROKININ-1-ANTAGONISTEN

Verfahren zur Herstellung von substituierten und unsubstituierten 2-Carbamoyl-nicotin- und 3-Chinolincarbonsäuren

AROMATISCHE DIAMID-DERIVATE ODER IHRE SALZE, CHEMIKALIEN FÜR DIE LANDWIRTSCHAFT/DEN GARTENBAU UND VERFAHREN ZU IHRER ANWENDUNG

ADAMANTANDERIVATE

New aryl amide compounds are kinase inhibitors useful for the treatment and/or prophylaxis of e.g. tumors, psoriasis, rheumatoid arthritis, contact dermatitis, inflammations, endometriosis, scar and benign prostatic hyperplasia

Aryl amide compounds (I) and their salts, derivatives, solvates and/or stereoisomers including their mixtures in all ratios are new. Aryl amide compounds (I) of formula (Ar 1>-N(R 2>)-CH(=Y)-Ar 2>-Z-Ar 3>) and their salts, derivatives, solvates and/or stereoisomers including their mixtures in all ratios are new. Ar 1>-Ar 3>aromatic (optionally substituted with R 1>) or Het; Het : 1-2 aromatic heterocyclic ring with 1-4 N-, O- and/or S-; R 1>H, A, aryl, OR 4>, SR 4>, Oaryl, Saryl, N(R 4>) 2, NHaryl, Hal, NO 2, CN, (CH 2) mCOOR 4>, (CH 2) mCOOaryl, (CH 2) mCON(R 4>) 2, (CH 2) mCONHaryl, COR 4>, COaryl, S(O) mA, S(O) maryl, NHCOA, NHCOaryl, NHSO 2A, NHSO 2aryl, SO 2N(R 4>) 2, O(CH 2) n, N(R 4>) 2, O(CH 2) nNHR 3>, O(CH 2) n-oxo-piperazine, O(CH 2) n-oxomorpholine, O(CH 2) n-oxopyrrolidine, O(CH 2) nC(CH 2) 2(CH 2) nN(R 4>) 2, N(CH 2) nC(CH 3) 2(CH 2) nN(R 4>) 2, O(CH 2) nN(R 4>)SO mA, O(CH 2) nN(R 4>)SO mN(R 4>)A, O(CH 2) nN(R 4>)SO maryl, (CH 2) nN(R 4>)SO mA, (CH 2) nN(R 4>)SO mN(R 4>)A, ...

Verfahren zur Herstellung von Pyridinalkoholcarbamatund-thioncarbamatderivaten und deren(py)-N-Oxyden

DERIVATE DES PYRIDO ECKIGE KLAMMER AUF 2,3D ECKIGE KLAMMER ZU PYRIMIDINS

HETEROCYCLISCHE AMIDE, VERFAHREN ZU DEREN HERSTELLUNG UND DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL

AMIDES AND THEIR USE AS INSECTICIDES

... 1354571 Insecticidal application of acrylic acid amides BEECHAM GROUP Ltd 17 Dec 1971 [13 Jan 1971] 1615/71 'Heading A5E [Also in Division C2] Insecticidal compositions contain a compound of the formula: where R is alkyl of 1-4 carbon atoms and R' is a monocyclic carbocyclic or heterocyclic group which may carry one or more ring substituents, mixed with a suitable liquid or solid vehicle.

HETEROCYCLIC AMIDES PROCESSES FOR THEIR PREPARATION AND PHARMA CEUTICAL COMPOSITIONS CONTAINING THEM

... 1428493 Nicotinamides and pyrimidinecarboxamides SCIENCE UNION ET CIE SOC FRANCAISE DE RECHERCHE MEDICALE 2 May 1974 [2 May 1973] 20842/73 Heading C2C The invention comprises nicotinamides and pyrimidinecarboxamides of the formula wherein X is N or CH; n is 0 or 1; and R is -CH(R 1 )CH 2 NR 2 R 3 , -CH(NR 2 R 3 )CH 2 R 1 or a 1-R 4 -pyrrolidin-2(or 3)-yl radical, wherein R 1 is H or CH 3 , R 2 and R 3 each are C 1 -C 6 alkyl, or R 2 and R 3 together are C 4 -C 7 polymethylene, which is optionally interrupted by an oxygen atom, and R 4 is C 1 -C 20 acyclic hydrocarbon, C 3 -C 7 cycloalkyl or Ar-A or wherein A is a single bond or C 1 -C 6 acyclic hydrocarbon, and Ar and R11 each are phenyl optionally substituted by alkoxy, methylenodioxy, ethylenedioxy or trimethylenedioxy radicals; and acid addition salts thereof. The compounds are prepared by either reacting acid halides of the Formula IV wherein Z is Cl, Br or OCOOY, where Y is C 1 -C 6 alkyl with amines of the formula and deacetylating ...

ACIDIC AMINO ACID DIAMIDE DERIVATIVE

CHEMICAL COMPOUNDS

Novel 2-methyl-pyridine-4-carboxylic acid derivatives and process for the manufacture thereof

The invention comprises 2-methyl-pyridine-4-carboxylic acid hydrazides of the general formula wherein X is a hydrogen or halogen atom and R1, R2 and R3 may each be a hydrogen atom or an alkyl, aralkyl or alkenyl group containing not more than 7 carbon atoms, and salts thereof. They may be prepared by reacting compounds of the general formula wherein X is hydrogen or halogen and R represents a halogen atom or an alkoxy group, or a hydrohalide salt thereof, with a hydrazine the Rs being as defined above, or a hydrate or salt thereof; if desired, when X is a halogen, the halogen in the 6-position in the resulting product may be replaced by hydrogen according to methods known per se. The unsubstituted hydrazine or a hydrate or salt thereof is preferably condensed with an ester of the methylpyridine carboxylic acid, the hydrate being normally used with a solvent. The substituted hydrazines and salts thereof are preferably ...

Sensors for neutral molecules

PROCESS FOR THE PREPARATION OF 5-ALKYLPYRIDINE DERIVATIVES HAVING A TETRAZOLE RADICAL

... 1346379 Substituted pyridyl- and pyridylmethyl-tetrazoles BANYU PHARMACEUTICAL CO Ltd and H HIDAKA 4 April 1972 [9 April 1971] 15398/72 Heading C2C Compounds of formula wherein R is C 1-9 alkyl and n is 0 or 1 are prepared by reacting a 2-cyano- or 2-cyanomethyl- 5-alkylpyridine with an inorganic azide. Intermediates also prepared are 2-X-5-butylpyridines, where X is COCl, CONH 2 , CH 2 OH or CH 2 Cl.

Novel compounds

Substituted heteroaryl fungicides

The substituted heteroaryl compounds of this invention are good fungicides. In particular, they possess especially good activity against Bean Powdery Mildew.

Chemical compounds

Chemical compounds

CEPHALOSPORIN ANTIBIOTICS

AMINOALKYLBENZENE DERIVATIVES

Bis (carboxamide) derivative

Bis(carboxamide) derivatives being useful as histamine H2 receptor antagonists or anti-peptic ulcer agents are provided from certain dicarboxylic acid derivatives.

5-substituted aza-dibenzo-cycloheptenes and the preparation thereof

The invention comprises compounds of the formula wherein the dotted line represents an optional double bond, A represents hydrogen or one of the substituents halogen, trifluoromethyl, alkoxy, C1- 12 alkyl, hydroxy and acyloxy attached to one or more of the 6-, 7-, 8- and 9-positions, B represents, together with the carbon atoms to which it is attached, a pyridine ring and Z represents one of the groups in which either U and W are both hydrogen or U is a univalent group containing an amino group the nitrogen atom of which is separated from C-5 of the tricyclic nucleus by at least two carbon atoms and W is H or OH, and V is an oxygen atom or a divalent group containing an amino group the nitrogen atom of which is separated from C-5 of the tricyclic nucleus by at least two carbon atoms; and pharmaceutically acceptable acid addition salts thereof. The compounds wherein Z is other than a carbonyl group are prepared by (a) reacting a compound of the formula ...

Substituted pyridyl ureas and processes for their preparation

Novel compounds of formula in which R1 and R2 represent a halogen atom, an alkyl group having 1-6 carbon atoms, an alkoxy group having 1-6 carbon atoms, an amino group which may be acylated by carboxylic acids having 1-6 carbon atoms or carbonic acids, or a carbamoyl group, and wherein R2 may also represent a hydrogen atom, R3 and R4 represent a hydrogen atom, an alkyl group having 1-6 carbon atoms or a phenyl group, and R5 represents a hydrogen atom or an alkyl group having 1-6 carbon atoms, are prepared (a) by reacting an amine of Formula II (1) with an isocyanate of formula R3NCO in molar quantities in the presence of a solvent at a temperature of 0 DEG to 100 DEG C.; (2) with a carbamic acid halide of formula HalOCNR3R4 either in molar quantities in the presence of an acid binding agent, or using 2 mols. of amine per mol. of acid halide, in the presence of a solvent at a temperature of 0 DEG to 180 DEG C.; (3) with a carbamic acid ester of formula ...

Sensors for neutral molecules

FUNGICIDES

3,6-dichloro - 2 - picolinic acid compounds

The invention comprises 3,6-dichloro-2-picolinic acid derivatives of the formula in which Y is a carboxylic acid, cyano, carboxylic acid salt, carboxylic acid hydrazide, carboxylic acid ester, or carboxylic acid amide group. 3,6-Dichloro-2-picolinic acid is prepared by heating 3,6-dichloro-2-(trichloromethyl) pyridine in the presence of a mineral acid. Salts and esters are obtained by treating the acid with a base or hydroxy compound. Amides and hydrazides are obtained by treating the ester with an appropriate nitrogen base. The cyano compound is obtained by heating the amide with phosphorus pentoxide. The 3,6-dichloro-2-(trichloromethyl) pyridine is obtained by photochlorinating 3-chloro-2-(trichloromethyl) pyridine at 120 DEG to 130 DEG C.ALSO:Herbicidal compositions contain as active ingredient, a 3, 6-dichloro-2-picolinic acid compound of the formula:- in which Y is a carboxylic acid, carboxylic acid salt, ester, amide or hydrazide, or a cyano ...

4-MEMBERED RING CARBOXAMIDES USED AS NEMATICIDES

Piperazine derivatives for the treatment of HIV infections.

Pyridine matrix metalloproteinase inhibitors.

PROCESS FOR THE PREPARATION OF 4-CARBONYL)AMINO]-3-FLUOROPHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE, ITS SALTS AND MONOHYDRATE

The present invention relates to a process for preparing 4-{4-[({[4-chloro-3-(trifluoromethyl)-phenyl]amino}carbonyl)amino]-3-fluorophenoxy}-N-methylpyridine-2-carboxamide, its salts and monohydrate. 2. The process of for preparing the monohydrate of the compound of the formula (I) wherein the salt of the compound of the formula (I) is then treated with an aqueous basic solution to precipitate the monohydrate of the compound of the formula (I).3. The process of wherein the monohydrate of the compound of the formula (I) precipitates at a temperature of from 35° C. to 45° C.4. The process of or for preparing of the compound of the formula (I) wherein the monohydrate is dried under reduced pressure until the compound of the formula (I) is formed.5. The process of any of to wherein the solution comprising the solved compound of the formula (I) and what from the salt of the compound of the formula (I) precipitates is the reaction mixture or is a separate solution of the compound of the formula (I) prepared after isolation of the compound of the formula (I) from the reaction mixture.6. The process of any of to wherein the acid is generated in situ in the reaction mixture after the compound of the formula (I) is formed by adding to the reaction mixture a protic substance and an acid precursor.7. The process of wherein the acid is generated in situ in the reaction mixture after the compound of the formula (I) is formed by adding to the reaction mixture an alcohol and an acylchloride.8. The process of wherein the alcohol is ethanol and the acylchloride is acetylchloride.11. The process of or wherein the compound of the formula (II) is used in a solution of a suitable organic solvent which solution is prepared by neutralization the hydrochloric acid salt of the compound of the formula (II) with a base.12. The process of any of to wherein the compound of the formula (II) it is solved in a suitable organic solvent claim 7 , treated with an acid which is generated in situ by ...

METHOD FOR PRODUCING CARBOXYLIC ACID AMIDE

A carboxamide can be produced in a high yield by a method for producing a carboxamide, for example, represented by formula (4): 1. A method for producing a carboxamide , the method comprising allowing a carboxylic acid ester , an amine , and a formamide compound corresponding to the amine to react in the presence of a metal alkoxide.3. The method according to claim 2 , wherein the step is a step of performing the reaction in a solvent.4. The method according to claim 3 , wherein the solvent is an alcohol solvent.5. The method according to claim 2 , wherein the metal alkoxide is an alkali metal alkoxide.6. The method according to claim 2 , wherein the step is a step performed under an increased pressure condition.7. The method according to claim 2 , wherein Rin each of formulae (2) claim 2 , (3) and (4) is a hydrogen atom or a C-Calkyl group.8. The method according to claim 2 , wherein Rin formula (1) is a C-Calkyl group.9. The method according to claim 3 , wherein the metal alkoxide is an alkali metal alkoxide.10. The method according to claim 3 , wherein the step is a step performed under an increased pressure condition. The present invention relates to a method for producing a carboxamide.Carboxamides are important compounds as a variety of chemical products such as active ingredients of medicines and pesticides, and electronic materials, and synthetic intermediates thereof (see, for example, WO2004/065374).In WO2004/065374 is disclosed a method in which ethyl 4,5-bis(4-methoxyphenyl)-1,3-oxazole-2-carboxylate, which is a carboxylic acid ester, is allowed to react with formamide in the presence of sodium methoxide, which is a metal alkoxide, to give 4,5-bis(4-methoxyphenyl)-1,3-oxazole-2-carboxamide, which is a carboxamide, in a yield of 71.9% (see Example 2).However, the method is not necessarily satisfactory in the yield of the carboxamide to be obtained.Thus, new methods by which a carboxamide can be produced from a carboxylic acid ester in a high yield have ...

Fluro substituted Omega-Carboxyaryl Diphenyl Urea for the Treatment and Prevention of Diseases and Conditions

A compound of Formula (I): 154-. (canceled)562. A compound claim where the methylamide group is substituted with a hydroxyl group.571. A pharmaceutical composition comprising a compound of claim and a physiologically acceptable carrier.581. A pharmaceutical composition for the treatment of a cancerous cell growth comprising a compound of claim and a physiologically acceptable carrier for treating cancer.605. A compound claim where either urea nitrogen atom of the compound of formula I is substituted with a hydroxyl group.627. A compound claim where the pyridine nitrogen atom is in the n-oxide form and the methylamide functionality is substituted with a hydroxyl group. This application is a continuation application of U.S. application Ser. No. 10/895,985 filed Jul. 22, 2004 which claims the benefit of the filing date of U.S. Provisional Application Ser. No. 60/489,102 filed Jul. 23, 2003 and U.S. Provisional Application Ser. No. 60/540,326 filed Feb. 2, 2004.This invention relates to novel compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for treating diseases and conditions mediated by abnormal VEGFR, PDGFR, raf, p38, and/or flt-3 kinase signaling, either alone or in combination with anti-cancer agents.Activation of the ras signal transduction pathway indicates a cascade of events that have a profound impact on cellular proliferation, differentiation, and transformation. Raf kinase, a downstream effector of ras, is recognized as a key mediator of these signals from cell surface receptors to the cell nucleus (Lowy, D. R.; Willumsen, B. M. 1993, 62, 851; Bos, J. L. 1989, 49, 4682). It has been shown that inhibiting the effect of active ras by inhibiting the raf kinase signaling pathway by administration of deactivating antibodies to raf kinase or by co-expression of dominant negative raf kinase or dominant negative MEK, the substrate of raf kinase, leads to the reversion of transformed cells to the normal ...

NOVEL AMIDO DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS

The present invention relates to novel compounds of Formula (I), wherein X, X, X, X, Aand Bare defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR4”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR4 receptors. 2. A compound according to claim 1 , which can exist as optical isomers claim 1 , wherein said compound is either the racemic mixture or one or both of the individual optical isomers.3. A compound according to claim 1 , wherein said compound is:N-(3-Chloro-4-(pyrimidin-2-yloxy)phenyl)picolinamideor a pharmaceutically acceptable acid or base addition salt thereof,a stereochemically isomeric form thereof and an N-oxide form thereof.4. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to to and a pharmaceutically acceptable carrier and/or excipient.5. A method of treating or preventing a condition in a mammal claim 1 , including a human claim 1 , the treatment or prevention of which is affected or facilitated by the neuromodulatory effect of mGluR4 allosteric modulators claim 1 , comprising administering to a mammal in need of such treatment or prevention claim 1 , an effective amount of a compound/composition according to to .6. A method of treating or preventing a condition in a mammal claim 1 , including a human claim 1 , the treatment or prevention of which is affected or facilitated by the neuromodulatory effect of mGluR4 positive allosteric modulators claim 1 , comprising administering to a mammal in need of such treatment or prevention claim 1 , an effective amount of a compound/composition according to to .7. A method useful for treating or preventing central nervous system disorders selected from the group consisting of: addiction claim 1 , tolerance or dependence claim 1 , affective disorders claim 1 , such as depression and anxiety claim 1 , psychiatric ...

TARGETED CORRECTION OF A GENETIC DEFECT IN CANCER THERAPY

The present document describes a cancer mutation-selective chemosensitizer that comprise compounds for restoring association between mutated keap1 protein and Nrf2 protein, and inhibition of Nrf2 functions. The present document also describes composition of matter containing the compounds, as well as methods of medical treatment for treating diseases such as cancer with the compounds. 3. The mutation-selective chemosensitizer of claim 1 , wherein said compound corrects a Keap1 mutation to restore interaction between a mutated Keap1 protein and said Nrf2 protein.10. A pharmaceutical composition for the inhibition of a Nrf2 protein which comprises a therapeutically effective amount of a compound of formula (I) as defined in claim 1 , in association with a pharmaceutically acceptable carrier.11. A pharmaceutical composition for overcoming drug resistance in cancer chemotherapy and for the inhibition of tumor growth which comprises a therapeutically effective amount of a compound of formula (I) as defined in claim 1 , in association with a pharmaceutically acceptable carrier.12. A method of treating and/or preventing a disease which involves the abnormal activation or expression of a Nrf2 protein comprising administering a therapeutically effective amount of the compound of formula (I) as defined in of .13. A method of treating a cancer in a subject in need thereof comprising administering a therapeutically effective amount of a compound of formula (I) as defined in of .14. The method of claims 13 , wherein said cancer is chosen from liver cancer claims 13 , lung cancer claims 13 , breast cancer claims 13 , prostate cancer claims 13 , colon cancer claims 13 , neuroblastoma or leukemia. This application claims priority of U.S. provisional patent application U.S. 61/557,646, filed 9 Nov. 2011, the specification of which is hereby incorporated by reference.(a) FieldThe subject matter disclosed generally relates to a mutation-selective chemosensitizer for overcoming ...

RATIONALLY IMPROVED ISONIAZID AND ETHIONAMIDE DERIVATIVES AND ACTIVITY THROUGH SELECTIVE ISOTOPIC SUBSTITUTION

The present invention relates to the use of isotopically labeled derivatives of isoniazid, ethionamide and related compounds as effective therapy for the treatment of mycobacterial diseases, including 144-. (canceled)46. The method according to wherein said NHNHgroup is isotopically labeled with two N atoms.47. The method according to wherein said compound contains at least one isotopically labeled atom selected from the group consisting of carbon-13 claim 45 , nitrogen-15 claim 45 , oxygen-17 and oxygen-18 in the exocyclic acyl hydrazide moiety of the compound.49. The method according to wherein said compound has an isotopically labeled carbon-13 claim 45 , oxygen-17 or oxygen-18 atom.50. The method according to wherein said compound has an isotopically labeled carbon-13 atom.51. The method according to wherein said compound has an isotopically labeled oxygen-17 atom.52. The method according to wherein said compound has an isotopically labeled oxygen-18 atom.53. The method according to wherein said compound has an isotopically labeled carbon-13 atom and an isotopically labeled oxygen-18 atom.54. The method according to wherein said compound has an isotopically labeled nitrogen-15 atom.55MycobacteriumMycobacterium tuberculosis.. The method according to wherein said infection is56. The method according to wherein said infection is latent.57. The method according to wherein said infection is active.58. The method according to wherein said infection is miliary.59. The method according to wherein said infection is extrapulmonary.60. The method according to wherein said infection is renal.62. The method according to wherein said compound is administered in pulmonary dosage form.63. The method according to wherein said compound is administered is oral dosage form.64. The method according to wherein said compound is administered in parenteral dosage form. This application claims the benefit of priority of U.S. provisional application Ser. No. 61/127,150, filed May 9, 2008 ...

AROMATIC COMPOUNDS WITH SULFUR CONTAINING LIGANDS

Compounds useful as nutritional supplements, antioxidants, heavy metal chelators and/or as intermediates for producing other related compounds with like uses have a formula: 3. The compound of wherein n=2.4. The compound of wherein R═H.5. The compound of wherein n=3.6. The compound of wherein R═H.7. The compound of wherein n=4.8. The compound of wherein R═H.10. The compound of wherein n=2.11. The compound of wherein R═H.12. The compound of wherein n=3.13. The compound of wherein R═H.14. The compound of wherein n=4.15. The compound of wherein R═H. This application is a continuation-in-part of U.S. patent application Ser. No. 13/565,047 filed 2 Aug. 2012, which is a continuation of U.S. patent application Ser. No. 12/731,415 filed on 25 Mar. 2010, the full disclosure of both is incorporated herein by reference.The present invention relates generally to novel aromatic compounds useful as nutritional supplements, antioxidants, heavy metal chelators and/or also as intermediates for producing other useful compounds of this type.Free radicals are unstable oxygen-containing molecules that negatively interact with other molecules in the body, in a process called oxidation. High levels of free radicals and oxidation can lead to oxidative stress. Moderate oxidative stress can trigger apoptosis: a genetically determined process of cell self destruction marked by fragmentation of nuclear DNA. More intensive oxidative stress may cause widespread necrosis or cell death.The body naturally fights oxidation by producing glutathione (GSH). Glutathione is a tripeptide composed of three amino acid residues: glutamic acid, cysteine and glycine. Glutathione is found in all cells in the body, including the bile, the epithial lining fluid of the lungs and in the blood. Glutathione is the smallest intracellular protein thiol molecule in the cells (that is: a molecule containing an —SH or sulfhydryl group). This characteristic emphasizes its potent antioxidant action and supports a multi- ...

Novel Phenylamino Isonicotinamide Compounds

The invention provides novel compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer, restenosis and inflammation. 113-. (canceled)15. A method for treating hyperproliferative diseases related to the hyperactivity of MEK as well as diseases modulated by the MEK cascade in mammals , comprising administering to a subject a compound according to in which radicals not designated in greater detail have the meaning indicated for the Formula (I) according to but in which:in Subformula IAX is NH,{'sup': '1', 'Ris Hal, methyl or ethyl,'}{'sup': '2', 'Ris hydrogen, Hal, methoxy or acetylene,'}{'sup': '3', 'Ris hydrogen or Hal,'}{'sup': '4', 'Ris hydrogen or Hal,'}{'sup': 5', '6, 'R, Rare OH,'}Hal is F, Cl, Br or I,in Subformula IBX is NH,{'sup': '1', 'Ris Hal,'}{'sup': '2', 'Ris hydrogen or Hal,'}{'sup': '3', 'Ris hydrogen or Hal,'}{'sup': '4', 'Ris hydrogen or Hal,'}{'sup': 5', '6, 'R, Rare OH,'}Hal is F, Cl, Br or I,in Subformula ICX is NH,{'sup': '1', 'Ris F, Cl, methyl or ethyl,'}{'sup': '2', 'Ris hydrogen, I, Br, methoxy or acetylene,'}{'sup': '3', 'Ris hydrogen or Hal,'}{'sup': '4', 'Ris hydrogen or Hal,'}{'sup': 5', '6, 'R, Rare OH,'}Hal is F, Cl, Br or I,in Subformula IDX is NH,{'sup': '1', 'Ris F, Cl, methyl or ethyl,'}{'sup': '2', 'Ris hydrogen, I, Br, methoxy or acetylene,'}{'sup': '3', 'Ris hydrogen or F,'}{'sup': '4', 'Ris hydrogen or Cl'}{'sup': 5', '6, 'R, Rare OH,'}in Subformula IEX is NH,{'sup': '1', 'Ris F or Cl,'}{'sup': '2', 'Ris I or Br,'}{'sup': '3', 'Ris hydrogen or F,'}{'sup': '4', 'Ris hydrogen or Cl'}{'sup': 5', '6, 'R, Rare OH,'}in Subformula IFX is NH,{'sup': '1', 'Ris F or Cl,'}{'sup': '2', 'Ris I or Br,'}{'sup': '3', 'Ris hydrogen or F,'}{'sup': '4', 'Ris hydrogen or Cl,'}{'sup': 5', '6, 'R, Rare OH,'}in Subformula IGX is NH,{'sup': '1', 'Ris F or Cl,'}{'sup': '2', 'Ris I or Br,'}{'sup': '3', 'Ris hydrogen,'}{'sup': '4', 'Ris hydrogen,'}{'sup': 5', '6, 'R, Rare OH,'}and in ...

Inhibitors and Methods of Inhibiting Bacterial and Viral Pathogens

Compounds, pharmaceutical compositions and methods for treating viral and bacterial infections, by administering certain thiourea compounds, specifically acylthiourea, carboximidoylthiourea and S-alkyl isothiourea derivatives and analogs, in therapeutically effective amounts are disclosed. 2. The composition of claim 1 , wherein Ris hydrogen.3. The composition of claim 1 , wherein Ris chloro.4. The composition of claim 1 , wherein Ris hydrogen.5. The composition of claim 1 , wherein Ris trifluoromethyl.6. The composition of claim 1 , wherein Ris amino.7. The composition of claim 1 , wherein Ris methylamino.8. The composition of claim 1 , wherein Ris hydrogen.9. The composition of claim 1 , wherein Ris methoxy.10. The composition of claim 1 , wherein Ris hydrogen.11. The composition of claim 1 , wherein the compound of Formula I is selected from the group consisting of: N-[(4-amino-3-methoxy-phenyl)carbamothioyl]-4-tert-butyl-benzamide; N-[(4-amino-2-chloro-phenyl)carbamothioyl]-4-tert-butyl-benzamide hydrochloride; 4-tert-butyl-N-[[2-chloro-4-(methylamino)phenyl]-carbamothioyl]benzamide hydrochloride; 4-tert-butyl-N-[(2-chloro-5-methyl-phenyl)-carbamothioyl]benzamide; 4-tert-butyl-N-[(2-chloro-6-methyl-phenyl)-carbamothioyl]benzamide; 4-tert-butyl-N-[[2-chloro-3-(trifluoromethyl)phenyl]-carbamothioyl]benzamide; N-[(4-amino-3-methoxy-phenyl)carbamothioyl]-4-tert-butyl-benzamide hydrochloride; 4-tert-butyl-N-[(2-chloro-3-methyl-phenyl)-carbamothioyl]benzamide; 4-tert-butyl-N-[[4-(methylamino)phenyl]-carbamothioyl]benzamide hydrochloride; 4-tert-butyl-N-[[2-chloro-4-(dimethylamino)phenyl]-carbamothioyl]benzamide hydrochloride; 4-tert-butyl-N-[[2-chloro-5-(trifluoromethoxy)phenyl]-carbamothioyl]benzamide; 4-tert-butyl-N-[[4-(3-pyridylamino)phenyl]-carbamothioyl]benzamide hydrochloride; 4-tert-butyl-N-[(2-chlorophenyl)carbamothioyl]-benzamide; 4-tert-butyl-N-(o-tolylcarbamothioyl)-benzamide; 4-tert-butyl-N-[[2-chloro-5-(trifluoromethyl)phenyl]-carbamothioyl]benzamide; N ...

PHOTOLABILE CAGED TRANSITION METAL COMPLEXES AND METHODS OF USING THE SAME

The present invention provides compounds of Formula I: 2. The compound of claim 1 , wherein Z is absent.3. The compound of claim 1 , wherein Z is a transition metal.4. The compound of claim 1 , wherein Z is a transition metal selected from the group consisting of copper claim 1 , platinum claim 1 , iron and zinc.5. The compound of claim 1 , wherein at least one adjacent pair of Rand Rtogether form a heteroaryl selected from the group consisting of pyrimidine claim 1 , thiazole claim 1 , thiophene claim 1 , isoquinoline claim 1 , imidazole claim 1 , and pyrroline.6. The compound of claim 1 , wherein Ris selected from the group consisting of: H claim 1 , alkyl claim 1 , alkoxy claim 1 , halo claim 1 , and sulfonate.7. The compound of claim 1 , wherein Ris selected from the group consisting of: H claim 1 , alkyl claim 1 , alkoxy claim 1 , halo claim 1 , and sulfonate.8. The compound of claim 1 , wherein Ris selected from the group consisting of: H claim 1 , alkyl claim 1 , alkoxy claim 1 , halo claim 1 , and sulfonate.9. The compound of claim 1 , wherein Ris selected from the group consisting of: H claim 1 , alkyl claim 1 , alkoxy claim 1 , halo claim 1 , and sulfonate.10. The compound of claim 1 , wherein Rand Rtogether form oxo.11. The compound of claim 1 , wherein each Ris independently selected from the group consisting of: H claim 1 , alkyl claim 1 , alkoxy claim 1 , halo claim 1 , and sulfonate.12. The compound of claim 1 , wherein each Ris independently selected from the group consisting of: H claim 1 , alkyl claim 1 , alkoxy claim 1 , halo claim 1 , and sulfonate.13. The compound of claim 1 , wherein each Ris independently selected from the group consisting of: H claim 1 , alkyl claim 1 , alkoxy claim 1 , and halo.14. The compound of claim 1 , wherein each Ris independently selected from the group consisting of: H claim 1 , alkyl claim 1 , alkoxy claim 1 , and halo.16. A composition comprising a compound of in a pharmaceutically acceptable carrier.1718-. ( ...

SORAFENIB DIMETHYL SULPHOXIDE SOLVATE

The present invention provides dimethyl sulphoxide solvate of 4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N-methylpyridine-2-carboxamide, process for its preparation, pharmaceutical composition comprising it and its use for the treatment of cancer. The present invention also provides a novel HPLC method for the identification, quantification and isolation of related substances of sorafenib. 2. Sorafenib dimethyl sulphoxide solvate according to further characterized by X-ray diffraction peaks at d-spacing 5.36 claim 1 , 4.47 claim 1 , 4.44 claim 1 , 3.26 and 3.14 Å.3. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by X-ray diffraction pattern as depicted in .4. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by DSC thermogram having endotherms at about 123.69° C. and about 202.54° C.5. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by DSC thermogram as depicted in .6. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by X-ray diffraction pattern as depicted in and DSC thermogram as depicted in .7. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by TGA as depicted in .8. Sorafenib dimethyl sulphoxide solvate of Formula III characterized by IR spectrum as depicted in .9. Sorafenib dimethyl sulphoxide solvate of Formula III having purity greater than 99% by HPLC.11. The process according to claim 10 , wherein Sorafenib free base of Formula I is contacted with dimethyl sulphoxide at a temperature of about 15° C. to the reflux temperature of dimethyl sulphoxide.13. The process according to claim 12 , wherein the solvent is selected from the group consisting of water claim 12 , chlorinated hydrocarbons claim 12 , alcohols claim 12 , ketones claim 12 , alkyl acetates claim 12 , ethers and mixtures thereof.14. The process according to claim 12 , wherein sorafenib dimethyl sulphoxide solvate of Formula III is contacted with a solvent at a temperature of about −5° C. ...

ANTICANCER COMPOUNDS AND PREPARATION METHODS THEREOF

Two new compounds with anticancer effects of N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methyl-formamide)(4-pyridyloxy)phenyl]-thiourea and N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methyl-formamide)(4-pyridylthio)phenyl]-thiourea, and salts thereof are disclosed. Preparation methods of the two new compounds and pharmaceutical compositions containing the new compounds are further disclosed. Experimental studies show that the two new compounds can effectively inhibit the activity of Raf and VEGFR protein kinase, widely inhibit growth of various types of human tumor cell lines and further induce apoptosis of tumor cells. Human tumor heterograft model investigation proves that the two new compounds are effective antineoplastic agents, and can sharply inhibit growth of human liver cancer cells, lung cancer cells and intestinal cancer cells in vivo. Furthermore, the anticancer effects of the compounds are much better than that of Sorafenib. 2. A method for preparing the compound of claim 1 , the method comprising:(1) adding dimethyl formamide dropwise to a solution of pyridine-2-carboxylic acid in thionyl chloride at 40° C., stirring, then heating to 72° C., and stirring overnight; and cooling to room temperature after the reaction is completed, removing thionyl chloride under reduced pressure, adding toluene, evaporating to dryness under reduced pressure, and then adding toluene again, to obtain a solution of 4-chloropyridyl-2-carbonyl chloride in toluene;(2) adding the solution of 4-chloropyridyl-2-carbonyl chloride in toluene dropwise to an aqueous methylamine solution cooled to −5° C., and stirring when the temperature is below 20° C.; and then adding ethyl acetate and water, washing the organic layer with saturated saline, drying it over anhydrous sodium sulfate, and then concentrating to an orange oil, to obtain 4-chloro(2-pyridyl)-N-methylcarboxamide;{'sup': '˜', '(3) Under the protection of nitrogen, dissolving 4-aminophenol in dimethylformamide, then adding ...

Novel Process For The Preparation Of Roflumilast

A composition comprising: roflumilast having a purity of greater than or equal to 99% by weight, and N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide present (relative to roflumilast) in an amount greater than zero and less than 0.1% by weight. 121.-. (canceled)22. A composition comprising: roflumilast having a purity of greater than or equal to 99% by weight , and N-(3 ,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide present (relative to roflumilast) in an amount greater than zero and less than 0.1% by weight.23. The composition of claim 22 , wherein said roflumilast has a purity of greater than or equal to 99.8% by weight.24. The composition of claim 22 , wherein said N-(3 claim 22 ,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide is present (relative to roflumilast) in an amount greater than zero and less than 0.05% by weight.25. A pharmaceutical composition claim 22 , comprising: roflumilast having a purity of greater than or equal to 99% by weight; N-(3 claim 22 ,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide present (relative to roflumilast) in an amount greater than zero and less than 0.1% by weight; and pharmaceutically acceptable auxiliaries and/or excipients.26. The pharmaceutical composition of claim 25 , wherein said roflumilast has a purity of greater than or equal to 99.8% by weight.27. The pharmaceutical composition of claim 25 , wherein said N-(3 claim 25 ,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide is present (relative to roflumilast) in an amount greater than zero and less than 0.05% by weight.28. A pharmaceutical dosage form claim 25 , comprising: roflumilast having a purity of greater than or equal to 99% by weight; N-(3 claim 25 ,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide present (relative to roflumilast) in an amount greater than zero and less than 0.1% by weight; and pharmaceutically acceptable auxiliaries and/or excipients.29. The pharmaceutical ...

PROLYL HYDROXYLASE INHIBITORS AND METHOD OF USE

The present disclosure relates to HIF-1α prolyl hydroxylase inhibitors, compositions which comprise the HIF-1α prolyl hydroxylase inhibitors described herein and to methods for controlling, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, and anemia. 2. The compound according to claim 1 , wherein Ris —OR.3. The compound according to claim 2 , wherein Ris hydrogen.4. The compound according to claim 2 , wherein Ris methyl.5. The compound according to claim 1 , wherein Ris —NRR.6. The compound according to claim 5 , wherein Rand Rare each independently hydrogen or methyl.7. The compound according to claim 6 , wherein R is —NH.8. The compound {[5-(3-fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid.10. The composition according to claim 9 , wherein Ris —OR.11. The composition according to claim 10 , wherein Ris hydrogen.12. The composition according to claim 10 , wherein Ris methyl.13. The composition according to claim 9 , wherein Ris —NRR.14. The composition according to claim 13 , wherein Rand Rare each independently hydrogen or methyl.15. The composition according to claim 14 , wherein R is —NH.16. The composition according to claim 9 , wherein the compound is {[5-(3-fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid.18. A method for treating anemia claim 1 , comprising administering to a subject a compound according to .19. A method for treating anemia claim 9 , comprising administering to a subject a composition according to .20. A method for treating anemia claim 17 , comprising administering to a subject a compound according to . This application is a Continuation application of U.S. application Ser. No. 13/681,876, filed Nov. 20, 2012, which is a Continuation application of U.S. application Ser. No. 12/860,073, filed Aug. 20, 2010, which is a Continuation application of U.S. application Ser. No. 11/821,936, now U.S. Pat. No. 7,811,595 B2, filed Jun. 26, 2007, which claims the benefit of ...

SUBSTITUTED PHENOXYPYRIDINES

The present invention relates to substituted phenoxypyridine compounds of general formula (I) in which R1, R2 and R3 are as defined in the claims, to methods of preparing said compounds, to intermediates for the preparation of said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients. 2. The compound according to claim 1 , wherein:{'sub': 1', '6', '2', '6', '3', '6, 'claim-text': a halogen atom, or a', {'sub': 1', '6', '1', '6', '2', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '10', '1', '6', '1', '6', '1', '6', '1', '6', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '1', '6', '2', '1', '6', '2', '2', '2', '2', '2', '2, 'CN, C-C-alkyl-, halo-C-C-alkyl-, HN—C-C-alkyl-, R(R′)N—C-C-alkyl-, HO—C-C-alkyl, C-C-alkyl substituted with two OH groups, C-C-alkoxy-C-C-alkyl-, halo-C-C-alkoxy-C-C-alkyl-, C-C-cycloalkyl-C-C-alkyl-, 3- to 10-membered 3- to 7-membered heterocycloalkyl-C-C-alkyl-, aryl-C-C-alkyl-, heteroaryl-C-C-alkyl-, —C(═O)R, —C(═O)NH, —C(═O)N(H)R, —C(═O)N(R)R′, —C(═O)OH, —C(═O)OR, —NH, —N(H)R, —N(R)R′, —N(H)C(═O)H, —N(H)C(═O)R, —N(R)C(═O)R′, —N(H)C(═O)NH, —N(H)C(═O)N(H)R, —N(H)C(═O)N(R)R′, —N(R)C(═O)NH, —N(R)C(═O)N(H)R, —N(R)C(═O)N(R)R′, —N(H)C(═O)OR, —N(R)C(═O)OR, —NO, —N(H)S(═O)R, —N(R)S(═O)R′, —N(H)S(═O)NH, —N(H)S(═O)N(H)R, —N(H)S(═O)N(R)R′, —N(R)S(═O)NH, —N(R)S(═O)N(H)R′, —N(R)S(═O)N(R′)R″, —N(H)S(═O)R, —N(H)S(═O)—C3-C6-cycloalkyl, —N(R)S(═O)R′, —N(H)S(═O)NH, —N(H)S(═O)N(H)R, —N(H)S(═O)N(R)R′, —N(R)S(═O)NH, —N(R)S(═O)N(H)R, —N(R)S(═O)N(R′)R″, —N═S(═O)(R)R′, —OH, C-C-alkoxy-, —OC(═O)H, —OC(═O)R, —OC(═O)NH, —OC(═O)N(H)R, —OC(═O)N(R)R′, —OC(═O)OR, —SH, C-C-alkyl-S—, —SC(═O)NH, —SC(═O)N(H)R, ...

AMPK-ACTIVATING HETEROCYCLIC COMPOUNDS AND METHODS FOR USING THE SAME

Disclosed are substituted pyridine compounds as well as pharmaceutical compositions and methods of use. One embodiment is a compound having the structure 2. The compound according to claim 1 , wherein D claim 1 , Dand Dare independently CH or C substituted by one of the w R.3. The compound according to claim 1 , wherein x is 0.4. The compound according to claim 1 , wherein the ring system denoted by “B” is arylene or heteroarylene.6. The compound according to claim 1 , wherein J is —NR— or —NRC(O)—.7. The compound according to claim 1 , wherein J is —C(O)NR— or —C(O)—.9. The compound according to claim 1 , wherein Rand Rtogether with the nitrogen to which they are bound form Hca.10. The compound according to wherein Ris -Cak. This application is a continuation of U.S. patent application Ser. No. 13/194,810, filed Jul. 29, 2011, which in turn claims the benefit of the earlier filing date of U.S. Provisional Patent Application Ser. No. 61/368,928, filed Jul. 29, 2010, each of which is hereby incorporated herein by reference in its entirety.1. FieldThis disclosure relates generally to compounds, pharmaceutical compositions and methods of use of the compounds and compositions containing them. This disclosure relates more particularly to certain substituted pyridine compounds and pharmaceutical compositions thereof, and to methods of treating and preventing metabolic disorders such as type II diabetes, atherosclerosis and cardiovascular disease using certain substituted pyridine compounds.2. Technical BackgroundThe kinase 5″-AMP-activated protein kinase (AMPK) is well established as an important sensor and regulator of cellular energy homeostasis. Being a multi-substrate enzyme, AMPK regulates a variety of metabolic processes, such as glucose transport, glycolysis and lipid metabolism. It acts as a sensor of cellular energy homeostasis and is activated in response to certain hormones and muscle contraction as well as to intracellular metabolic stress signals such as ...

Novel Ureas for the Treatment and Prevention of Cancer

A compound of Formula (I), salts thereof, prodrugs thereof, metabolites thereof, pharmaceutical compositions containing such a compound, and use of such compound and compositions to treat diseases mediated by multiple kinases, such as raf, VEGFR, PDGFR, FLT-3, and c-Kit. 2. The compound of claim 1 , wherein Y is O claim 1 , S claim 1 , or NR.3. The compound of claim 2 , wherein Y is O or S.4. The compound of claim 1 , wherein Z and Z′ are each CH.5. The compound of claim 1 , wherein Rand Rare each independently alkyl or halo.6. The compound of claim 5 , wherein Rand Rare each independently halo.7. The compound of claim 6 , wherein Rand Rare each independently F claim 6 , Cl claim 6 , or Br.8. The compound of claim 1 , wherein Ris hydrogen claim 1 , halo claim 1 , carboxyl claim 1 , carboxyl ester claim 1 , or aminocarbonyl.9. The compound of claim 8 , wherein Ris aminocarbonyl.10. The compound of claim 9 , wherein Ris methylaminocarbonyl.11. The compound of claim 1 , wherein m and n are each independently 0 or 1.17. The compound of claim 1 , wherein the compound is a pharmaceutically acceptable salt of hydrochloric acid claim 1 , hydrobromic acid claim 1 , sulfuric acid claim 1 , phosphoric acid claim 1 , methanesulfonic acid claim 1 , trifluoromethanesulfonic acid claim 1 , benzenesulfonic acid claim 1 , p-toluene sulfonic acid (tosylate salt) claim 1 , 1-napthalene sulfonic acid claim 1 , 2-napthalene sulfonic acid claim 1 , acetic acid claim 1 , trifluoroacetic acid claim 1 , malic add claim 1 , tartaric acid claim 1 , citric acid claim 1 , lactic acid claim 1 , oxalic acid claim 1 , succinic acid claim 1 , fumaric acid claim 1 , maleic acid claim 1 , benzoic acid claim 1 , salicylic acid claim 1 , phenylacetic acid claim 1 , or mandelic acid.18. A pharmaceutical composition comprising a compound of and a physiologically acceptable carrier.19. A method for preventing or treating a disease in a mammal that is mediated by protein kinanse claim 1 , comprising ...

PYRIDONE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES

Compounds useful in the treatment of mammalian cancers and especially human cancers according to Formula I are disclosed. 5. The compound of claim 4 , wherein R3 is C1-C6 alkyl claim 4 , C3-C8 branched alkyl claim 4 , C3-C8 cycloalkyl or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , enantiomer stereoisomer or tautomer thereof.6. The compound of claim 4 , wherein R3 is —NR6(R7) or R4 claim 4 , or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , enantiomer stereoisomer or tautomer thereof.76. A compound of any one of - wherein R1 is fluoro or H and n is 1.817. A compound of claims any one of - wherein R2 is C1-C6 alkyl or C3-C8 branched alkyl.12. The compound of claim 11 , wherein R3 is C1-C6 alkyl claim 11 , C3-C8 branched alkyl claim 11 , C3-C8 cycloalkyl or a pharmaceutically acceptable salt claim 11 , hydrate claim 11 , solvate claim 11 , enantiomer stereoisomer or tautomer thereof.13. The compound of claim 11 , wherein R3 is —NR6(R7) or R4 or a pharmaceutically acceptable salt claim 11 , hydrate claim 11 , solvate claim 11 , enantiomer stereoisomer or tautomer thereof.1413. A compound of any one of - wherein R1 is fluoro or H and n is 1.15914. A compound of claims any one of - wherein R2 is C1-C6 alkyl or C3-C8 branched alkyl.16. A compound selected from the group consisting of N-(4-((2-acetamidopyridin-4-yl)oxy)-2 claims 9 ,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1 claims 9 ,2-dihydropyridine-3-carboxamide claims 9 , N-(2 claims 9 ,5-difluoro-4-((2-propionamidopyridin-4-yl)oxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1 claims 9 ,2-dihydropyridine-3-carboxamide claims 9 , N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2 claims 9 ,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1 claims 9 ,2-dihydropyridine-3-carboxamide claims 9 , N-(2 claims 9 ,5-difluoro-4-((2-pivalamidopyridin-4-yl)oxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1 claims 9 ,2-dihydropyridine-3-carboxamide ...

VIRAL POLYMERASE INHIBITORS

Compounds of formula I: 2. The compound according to , or a pharmaceutically acceptable salt thereof , wherein X is O , and R , R , R , R , R , and Rare as defined in .5. The compound according to claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein Ris H or CF claim 4 , and Ris selected from:{'sub': '1-3', 'sup': '7', '—(C)alkylene-R;'}{'sup': '7', 'wherein Ris Het; wherein the Het is a 5- or 6-membered heterocycle containing 1 to 4 heteroatoms, each independently selected from N, O and S, or Het is a 9- or 10-membered heteropolycycle containing 1 to 4 heteroatoms, each independently selected from N, O and S;'}{'sub': '2', 'wherein each N heteroatom may, independently and where possible, exist in an oxidized state such that it is further bonded to an oxygen atom to form an N-oxide group and wherein each S heteroatom may, independently and where possible, exist in an oxidized state such that it is further bonded to one or two oxygen atoms to form the groups SO or SO;'}{'sub': 1-6', '1-6', '3-7', '2', '1-4', '3-7', '1-4', '3-7', '1-4', '2', '1-4', '1-6, 'wherein the Het is optionally substituted with 1 to 3 substituents each independently selected from halo, cyano, oxo, imino, —OH, —O—(C)alkyl, —O—(C)haloalkyl, (C)cycloalkyl, —NH, —NH(C)alkyl, —NH(C)cycloalkyl, —N((C)alkyl)(C)cycloalkyl, —N((C)alkyl), —NH—C(═O)(C)alkyl, (C)alkyl and Het, wherein the Het is a 5- or 6-membered heterocycle containing 1 to 4 heteroatoms, each independently selected from N, O and S.'}6. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from H claim 1 , F claim 1 , Cand CH.7. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from H claim 1 , F and CH.8. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from H claim 1 , F claim 1 , Cl claim 1 , CHand CN.9. The compound according to claim 1 , or ...

CYCLOALKYL GUANIDINE F1F0-ATPASE INHIBITORS AND THERAPEUTIC USES THEREOF

The invention provides cycloalkyl guanidine compounds that inhibit FF-ATPase, and methods of using cyclalkyl guanidine compounds as therapeutic agents in therapy, such as treating an immune disorder, inflammatory condition, or cancer. 2. The compound of claim 1 , wherein A is cycloalkylene claim 1 , that in addition to R claim 1 , is optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , cycloalkyl claim 1 , —N(R)COR claim 1 , —N(R)C(O)R claim 1 , —N(R)(R) claim 1 , —OR claim 1 , and —C(O)R.3. (canceled)4. The compound of claim 1 , wherein A is cyclobutylene claim 1 , cyclopentylene claim 1 , or cyclohexylene claim 1 , each of which is claim 1 , in addition to R claim 1 , optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , hydroxyl claim 1 , and —N(R)(R).5. The compound of claim 1 , wherein A is cyclohexylene.6. The compound of claim 1 , wherein Rrepresents independently for each occurrence halogen claim 1 , haloalkyl claim 1 , alkyl claim 1 , or C-Calkoxy.7. The compound of claim 1 , wherein Rrepresents independently for each occurrence chloro claim 1 , fluoro claim 1 , or trifluoromethyl.8. The compound of claim 1 , wherein Ris hydrogen.9. (canceled)10. The compound of claim 1 , wherein Ris —N(R)COR claim 1 , —N(R)C(O)R claim 1 , —N(R)C(O)N(R)(R) claim 1 , —N(R)SOR claim 1 , or —N(R)(R).11. The compound of claim 1 , wherein Ris —N(R)COR.12. The compound of claim 1 , wherein Ris —N(R)C(O)R.1316-. (canceled)17. The compound of claim 1 , wherein Ris aryl or aralkyl claim 1 , each of which is optionally substituted with 1 claim 1 , 2 claim 1 , or 3 substituents independently selected from the group consisting of halogen claim 1 , haloalkyl claim 1 , alkyl claim 1 , cycloalkyl claim 1 , and C-Calkoxy.18. The compound of claim 1 , wherein Ris phenyl optionally substituted ...

COMPOUNDS FOR TREATING PROLIFERATIVE DISORDERS

Disclosed are compounds and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and/or natural killer induction. Also, disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier. 2. The compound of claim 1 , wherein Xand Xare each an optionally substituted ethylene group.3. The compound of claim 1 , wherein Xand Xare each an optionally substituted ethylene group.5. The compound of claim 4 , wherein:{'sub': 1', '2, 'Rand Rare each an optionally substituted aryl or an optionally substituted heteroaryl;'}{'sub': 5', '6, 'Ris —H and Ris —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl; and'}{'sub': 3', '4, 'Rand Rare each an alkyl group.'}6. The compound of claim 4 , wherein{'sub': 1', '2, 'Rand Rare both an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl;'}{'sub': '5', 'Ris —H; and'}{'sub': '6', 'Ris —H or an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl.'}7. The compound of claim 4 , wherein{'sub': 13', '7', '8, 'Ris —C(R)(R)—;'}{'sub': 7', '8', '7', '8, 'Rand Rare each independently —H or an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, or Ris —H and Ris an optionally substituted aryl or an optionally ...

RADIOFLUORINATION METHOD

Provided by the present invention is a novel method for obtaining an F-labelled compound wherein said compound comprises an F-labelled pyridyl ring. The method of the invention is advantageous over the prior art methods as it provides these compounds in higher radiochemical yields than have been possible with previous methods. Also provided by the present invention is an F-labelled synthon useful in the method of the invention. 4) The method as defined in which further comprises the step:{'sup': 18', '18, '(ii) coupling the F-labelled synthon of Formula Y as defined herein with a cross-coupling partner in a transition metal-mediated coupling reaction to obtain an F-labelled product.'}5) The method as defined in wherein said transition metal is palladium.12) The method as defined in which is automated. The present invention relates to a method for radiosynthesis and more specifically a novel method for the synthesis of F-labelled compounds. The invention also relates to a novel synthon for use in the inventive method of synthesis.In order to expand the range of applications for positron emission tomography (PET) there is an interest in developing synthetic methods for new PET tracers, i.e. biologically useful compounds labelled with C, F or Br. Currently, the most widely-used of these radiotracers for PET imaging is F.Typically, the synthesis of a PET tracer including its purification should be completed within three half-lives of the radiotracer. F has a relatively short half-life of 109.7 minutes and as such methods for its incorporation into a PET tracer demands fast and high-yielding reactions that can be performed on a small scale and under mild conditions.Direct labelling is desirable as it introduces F at the last possible step. However, direct labelling tends only to be possible using [F]fluoride in a nucleophilic substitution reaction can require the presence of activating groups, proton-free conditions and typically high temperatures of above 100° C. The ...

PROCESSES AND INTERMEDIATES FOR CARBAMOYLPYRIDONE HIV INTEGRASE INHIBITORS

Processes are provided which create an aldehyde methylene, or hydrated or hemiacetal methylene attached to a heteroatom of a 6 membered ring without going through an olefinic group and without the necessity of using an osmium reagent. In particular, a compound of formula (I) can be produced from (II) and avoid the use of an allyl amine: (formulae I and II) where R, PP, Rand Rare as described herein. 122-. (canceled)24. The process of claim 23 , wherein in said compound of formula (I) claim 23 , R is —CHO.25. The process of claim 23 , wherein in said compound of formula (I) claim 23 , R is —CH(OH)(OR).30. The process according to wherein in said compound of formula (I) claim 23 , Ris H claim 23 , halogen claim 23 , hydroxy claim 23 , optionally substituted lower alkyl claim 23 , optionally substituted cycloalkyl claim 23 , optionally substituted lower alkenyl claim 23 , or optionally substituted lower alkoxy.32. The process of claim 23 , wherein said refunctionalizing step ii) comprises demethylating the intermediate of formula (V) to produce the compound of formula (I).33. The process of claim 23 , wherein said refunctionalizing step ii) comprises reacting the intermediate of formula (VI) with NaIOto produce the compound of formula (I).34. The process of claim 23 , wherein Ris H. The present invention comprises modifications of known processes for synthesizing compounds having HIV integrase inhibitory activity.WO 2006/116764 published 2 Nov. 2006, incorporated by reference in its entirety, describes various compounds and detailed synthetic schemes for their preparation. In particular, the 16, 27and 32steps involve the creation of a —CHO group from a double bond using a reagent which may include osmium tetroxide.Processes are provided which create an aldehyde methylene, or hydrated or hemiacetal methylene attached to a heteroatom of a 6 membered ring without going through an olefinic group and without the necessity of using an osmium reagent.The present invention ...

PROLYL HYDROXYLASE INHIBITORS AND METHODS OF USE

The present disclosure relates to HIF-1α prolyl hydroxylase inhibitors, compositions which comprise the HIF-1α prolyl hydroxylase inhibitors described herein and to methods for controlling, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD) heart failure, ischemia, and anemia. 132-. (canceled) This application is a Continuation Application of U.S. application Ser. No. 11/821,936, filed Jun. 26, 2007, which claims the benefit of Provisional Application Ser. No. 60/816,522 filed on Jun. 26, 2006, and the entire disclosures of Provisional Application Ser. No. 60/816,522 and U.S. application Ser. No. 11/821,936 are incorporated herein by reference in its entirely.The present disclosure relates, in some aspects, to HIF-1α prolyl hydroxylase inhibitor compounds and pharmaceutically acceptable salts thereof, compositions comprising the HIF-1α prolyl hydroxylase inhibitor compounds, and to methods for treating or controlling, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, and anemia.HIF-1α under normal healthy conditions wherein the cells have a sufficient supply of oxygen is readily converted to a degraded form by one of several prolyl hydroxylase enzymes, infer alia, EGLIN. When cells undergo hypoxia, this enzymatic transformation is slow or entirely stopped and HIF-1α begins to build up in the cell. When this build up of HIF-1α occurs, this protein combines with another factor, HIF-1β which together form an active transcription factor complex. This transcription factor then activates several biological pathways which are present as a response to and a means for alleviating the body's state of hypoxia. These responses include, inter alia, angiogenic, erythropoietic (EPO), glucose metabolism, and matrix alteration responses.In patients where there is a need for stimulating one or more of these responses, for example, in patients in need of increased tissue oxygen due to peripheral vascular ...

KINASE INHIBITORS AND METHODS OF THEIR USE

New compounds, compositions and methods of inhibition of Provirus Integration of Maloney Kinase (PIM kinase) activity associated with tumorigenesis in a human or animal subject are provided. In certain embodiments, the compounds and compositions are effective to inhibit the activity of at least one PIM kinase. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a serine/threonine kinase- or receptor tyrosine kinase-mediated disorder, such as cancer. 2. The method of claim 1 , wherein Y is substituted with one to three substituents selected from hydroxyl claim 1 , amino claim 1 , Calkyl claim 1 , and Chalo alkyl.3. The method of claim 2 , wherein Y is substituted with one to three substituents selected from methyl claim 2 , hydroxyl claim 2 , amino claim 2 , and CF.4. The method of claim 2 , wherein Ris hydrogen claim 2 , amino claim 2 , or fluoro.5. The method of claim 2 , wherein Ris pyridyl or phenyl.6. The method of claim 5 , wherein Ris phenyl substituted with up to three substituents selected from halo claim 5 , hydroxyl claim 5 , Calkoxy claim 5 , and Calkyl.7. The method of claim 5 , wherein Y is substituted with one to three substituents selected from methyl claim 5 , hydroxyl claim 5 , amino claim 5 , and CF; Ris hydrogen; and Ris phenyl substituted with up to three substituents selected from fluoro claim 5 , hydroxyl claim 5 , methyl claim 5 , ethyl claim 5 , methoxy claim 5 , and propoxy.8. The method of claim 7 , wherein Ris 2 claim 7 ,6-difluorophenyl.9. The method of claim 1 , wherein the compound is selected from the group consisting ofN-(4-((3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide;3-amino-N-(4-((1R,3R,4S,5S)-3-amino-4-hydroxy-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)picolinamide;N-(4-((3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide;3-amino-N-(4 ...

Catalytic Process for Production of Pyridine Carboxylic Acid Amides

An improved catalytic process for the production of pyridine carboxylic acid amides, by catalytic hydration reaction of pyridine nitriles with solid heterogeneous catalyst wherein the process involve effective utilization and recycling of the catalytic components, and reactants. 1. A process for producing pyridine carboxylic acid amide compounds , analogs , substituted forms , derivatives , or pharmaceutically acceptable salts , esters , prodrugs , solvates and hydrates thereof , the process comprising:a catalytic hydrolysis of pyridine nitrile compound with water in the presence of a solid heterogeneous catalyst, optionally in alcohol,wherein the catalyst, water and other reactant materials are reused and wherein the catalyst, when deactivated is regenerated and reused in the process.2. The process according to claim 1 , wherein the catalyst is selected from the group comprising oxides claim 1 , hydroxides claim 1 , carbonates claim 1 , bicarbonates claim 1 , nitrates claim 1 , sulphates claim 1 , halides claim 1 , acetates claim 1 , chelates claim 1 , complexes claim 1 , nanoparticles of metals from group IIA claim 1 , IIIB claim 1 , IVB claim 1 , VB claim 1 , VIB claim 1 , VIIB claim 1 , VIIIB claim 1 , IB claim 1 , IIB claim 1 , IIIA and IVA of the periodic table and mixtures thereof.3. The process according to claim 1 , wherein the catalyst is selected from the group comprising oxides claim 1 , hydroxides claim 1 , carbonates claim 1 , bicarbonates claim 1 , nitrates claim 1 , sulphates claim 1 , halides claim 1 , acetates claim 1 , chelates claim 1 , complexes claim 1 , nanoparticles of manganese claim 1 , cobalt claim 1 , nickel claim 1 , lead claim 1 , copper claim 1 , aluminium claim 1 , rhuthenium claim 1 , silver claim 1 , zinc claim 1 , cadmium claim 1 , iron claim 1 , molybdenum claim 1 , chromium claim 1 , magnesium claim 1 , vanadium claim 1 , zirconium claim 1 , indium and mixtures thereof.4. The process according to claim 1 , wherein the water used ...

SORAFENIB DERIVATIVES AS SEH INHIBITORS

The present invention provides compounds for the inhibition of soluble epoxide hydrolase and associated disease conditions. 2. The compound of claim 1 , wherein{'sup': '1', 'sub': 1-6', '1-6, 'Ris selected from the group consisting of halogen, Chaloalkyl and Chaloalkoxy;'}{'sup': 2', '2a', '2a', '2b, 'sub': 1-6', '1-6, 'Ris selected from the group consisting of Chaloalkyl, Chaloalkoxy, —C(O)ORand —C(O)NRR;'}{'sup': 2a', '2b, 'sub': 1-6', '3-8, 'Rand Rare each independently selected from the group consisting of H, Calkyl and Ccycloalkyl;'}X is selected from the group consisting of —CH— and —N—;subscript m is an integer from 1 to 3;{'sup': 2', '1, 'sub': '1-6', 'such that when X is —CH—, Ris —C(O)OH, and subscript m is 1, then Ris selected from the group consisting of halogen and Chaloalkyl;'}and salts and isomers thereof.3. The compound of claim 1 , wherein X is —CH—.4. The compound of claim 1 , wherein X is —N—.5. The compound of claim 1 , wherein Ris selected from the group consisting of —C(O)ORand —C(O)NRR.14. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.15. A method for inhibiting a soluble epoxide hydrolase claim 1 , the method comprising contacting the soluble epoxide hydrolase with a therapeutically effective amount of a compound of claim 1 , thereby inhibiting the soluble epoxide hydrolase.16. The method of claim 15 , wherein the compound further inhibits a kinase.17. The method of claim 16 , wherein the kinase is selected from the group consisting of Raf-1 and b-Raf.18. A method for monitoring the activity of a soluble epoxide hydrolase claim 1 , the method comprising contacting the soluble epoxide hydrolase with an amount of a compound of sufficient to produce a detectable change in the fluorescence of the soluble epoxide hydrolase by interacting with one or more tryptophan residues present in the catalytic site of said soluble epoxide hydrolase claim 1 , thereby monitoring the activity of the soluble ...

PICOLINAMIDE COMPOUNDS WITH FUNGICIDAL ACTIVITY

This disclosure relates to picolinamides of Formula I and their use as fungicides. 2. A compound according to claim 1 , wherein X and Y are hydrogen.3. A compound according to claim 2 , wherein Rand Rare independently chosen from hydrogen or alkyl.4. A compound according to claim 2 , wherein Rand Rare independently chosen from hydrogen or alkyl.5. A compound according to claim 2 , wherein Ris chosen from C-Calkyl claim 2 , aryl claim 2 , or alkenyl claim 2 , each optionally substituted with 0 claim 2 , 1 or multiple R.6. A compound according to claim 2 , wherein Ris chosen from alkyl or aryl claim 2 , each optionally substituted with 0 claim 2 , 1 or multiple R.7. A compound according to claim 2 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 2 , Rand Rare independently chosen from hydrogen or alkyl claim 2 , Ris chosen from C-Calkyl claim 2 , aryl claim 2 , or alkenyl claim 2 , each optionally substituted with 0 claim 2 , 1 or multiple R claim 2 , and Ris chosen from alkyl or aryl claim 2 , each optionally substituted with 0 claim 2 , 1 or multiple R.8. A compound according to claim 1 , wherein X is C(O)Rand Y is hydrogen.9. A compound according to claim 8 , wherein Rand Rare independently chosen from hydrogen or alkyl.10. A compound according to claim 8 , wherein Rand Rare independently chosen from hydrogen or alkyl.11. A compound according to claim 8 , wherein Ris chosen from C-Calkyl claim 8 , aryl claim 8 , or alkenyl claim 8 , each optionally substituted with 0 claim 8 , 1 or multiple R.12. A compound according to claim 8 , wherein Ris chosen from alkyl or aryl claim 8 , each optionally substituted with 0 claim 8 , 1 or multiple R.13. A compound according to claim 8 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 8 , Rand Rare independently chosen from hydrogen or alkyl claim 8 , Ris chosen from C-Calkyl claim 8 , aryl claim 8 , or alkenyl claim 8 , each optionally substituted with 0 claim 8 , 1 or multiple R claim 8 ...

PICOLINAMIDES AS FUNGICIDES

This disclosure relates to picolinamides of Formula I and their use as fungicides. 2. A compound according to claim 1 , wherein X and Y are hydrogen.3. A compound according to claim 2 , wherein Rand Rare independently chosen from hydrogen or alkyl.4. (canceled)5. A compound according to claim 2 , wherein Ris aryl claim 2 , optionally substituted with 0 claim 2 , 1 or multiple R.6. A compound according to claim 2 , wherein Ris chosen from alkyl or aryl claim 2 , each optionally substituted with 0 claim 2 , 1 or multiple R.7. A compound according to claim 2 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 2 , Ris aryl claim 2 , optionally substituted with 0 claim 2 , 1 or multiple R claim 2 , and Ris chosen from alkyl or aryl claim 2 , each optionally substituted with 0 claim 2 , 1 or multiple R.8. A compound according to claim 1 , wherein X is C(O)Rand Y is hydrogen.9. A compound according to claim 8 , wherein Rand Rare independently chosen from hydrogen or alkyl.10. (canceled)11. A compound according to claim 8 , wherein Ris aryl claim 8 , optionally substituted with 0 claim 8 , 1 or multiple R.12. A compound according to claim 8 , wherein Ris chosen from alkyl or aryl claim 8 , each optionally substituted with 0 claim 8 , 1 or multiple R.13. A compound according to claim 8 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 8 , Ris aryl claim 8 , optionally substituted with 0 claim 8 , 1 or multiple R claim 8 , and Ris chosen from alkyl or aryl claim 8 , each optionally substituted with 0 claim 8 , 1 or multiple R.14. A compound according to claim 1 , wherein X is hydrogen and Y is Q.15. A compound according to claim 14 , wherein Ris hydrogen.16. A compound according to claim 15 , wherein Ris alkoxy.17. A compound according to claim 16 , wherein Rand Rare independently chosen from hydrogen or alkyl.18. (canceled)19. A compound according to claim 16 , wherein Ris aryl claim 16 , optionally substituted with 0 claim 16 , 1 or ...

USE OF PICOLINAMIDE COMPOUNDS WITH FUNGICIDAL ACTIVITY

This disclosure relates to picolinamides of Formula I and their use as fungicides. 2. A composition according to claim 1 , wherein X is hydrogen and Y is Q.3. A composition according to claim 2 , wherein Ris alkoxy.4. A composition according to claim 3 , wherein Ris hydrogen.5. A composition according to claim 4 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 4 , optionally substituted with 0 claim 4 , 1 or multiple R.6. A composition according to claim 4 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 4 , each optionally substituted with 0 claim 4 , 1 or multiple R.7. A composition according to claim 4 , wherein Ris aryl claim 4 , optionally substituted with 0 claim 4 , 1 or multiple R.8. A composition according to claim 4 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 4 , optionally substituted with 0 claim 4 , 1 or multiple R claim 4 , Rand Rare independently chosen from hydrogen or alkyl claim 4 , each optionally substituted with 0 claim 4 , 1 or multiple R claim 4 , and Ris aryl claim 4 , optionally substituted with 0 claim 4 , 1 or multiple R.9. A composition according to claim 3 , wherein Ris chosen from —C(O)R claim 3 , or —CHOC(O)R.10. A composition according to claim 9 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 9 , optionally substituted with 0 claim 9 , 1 or multiple R.11. A composition according to claim 9 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 9 , each optionally substituted with 0 claim 9 , 1 or multiple R.12. A composition according to claim 9 , wherein Ris aryl claim 9 , optionally substituted with 0 claim 9 , 1 or multiple R.13. A composition according to claim 9 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 9 , Rand Rare independently chosen from hydrogen or alkyl claim 9 , each optionally substituted with 0 claim 9 , 1 or multiple R claim 9 , and Ris aryl claim 9 , optionally substituted with 0 claim ...

USE OF PICOLINAMIDE COMPOUNDS WITH FUNGICIDAL ACTIVITY

This disclosure relates to picolinamides of Formula I and their use as fungicides. 2. The composition according to claim 1 , wherein X is hydrogen and Y is Q.3. The composition according to claim 2 , wherein Ris alkoxy.4. The composition according to claim 3 , wherein Ris hydrogen.5. The composition according to claim 4 , wherein Rand Rare independently chosen from hydrogen or alkyl.6. The composition according to claim 4 , wherein Rand Rare independently chosen from hydrogen or alkyl.7. The composition according to claim 4 , wherein Ris chosen from C-Calkyl claim 4 , aryl claim 4 , or alkenyl claim 4 , each optionally substituted with 0 claim 4 , 1 or multiple R.8. The composition according to claim 4 , wherein Ris chosen from alkyl or aryl claim 4 , each optionally substituted with 0 claim 4 , 1 or multiple R.9. The composition according to claim 4 , wherein Rand Rare independently chosen from hydrogen or alkyl claim 4 , Rand Rare independently chosen from hydrogen or alkyl claim 4 , Ris chosen from C-Calkyl claim 4 , aryl claim 4 , or alkenyl claim 4 , each optionally substituted with 0 claim 4 , 1 or multiple R claim 4 , and Ris chosen from alkyl or aryl claim 4 , each optionally substituted with 0 claim 4 , 1 or multiple R.10. The composition according to claim 3 , wherein Ris chosen from —C(O)R claim 3 , or —CHOC(O)R.11. The composition according to claim 10 , wherein Ris alkyl claim 10 , optionally substituted with 0 claim 10 , 1 or multiple R.12. The composition according to claim 11 , wherein Rand Rare independently chosen from hydrogen or alkyl.13. The composition according to claim 11 , wherein Rand Rare independently chosen from hydrogen or alkyl.14. The composition according to claim 11 , wherein Ris chosen from C-Calkyl claim 11 , aryl claim 11 , or alkenyl claim 11 , each optionally substituted with 0 claim 11 , 1 or multiple R.15. The composition according to claim 11 , wherein Ris chosen from alkyl or aryl claim 11 , each optionally substituted with ...

INSECTICIDAL COMPOUNDS

The present invention relates to novel triazole derivatives of formula (I) having insecticidal activity, to processes and intermediates for preparing them, to insecticidal, acaricidal, nematicidal or molluscicidal compositions comprising them and to methods of using them to combat and control insect, acarine, nematode or mollusc pests (I) wherein Y, X, X 2 and Q are as defined in claim ; or salts thereof. 3. A compound of formula (I) according to wherein{'sub': '1', 'Xis hydrogen, fluorine or methoxy'}{'sub': 2', '2', '1, 'Xis hydrogen or cyano, with the condition that if Xis cyano, then Xis hydrogen,'}R is hydrogen, methyl or ethyl.4. A compound of formula (I) according to wherein{'sub': 1', '2, 'Xis methoxy and Xis hydrogen.'}5. A compound of formula (I) according to wherein{'sub': 2', '1, 'Xis cyano and Xis hydrogen.'}7. A method of controlling insects claim 1 , acarines claim 1 , nematodes or molluscs which comprises applying to a pest claim 1 , to a locus of a pest claim 1 , or to a plant susceptible to attack by a pest an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in .8. An insecticidal claim 1 , acaricidal claim 1 , nematicidal or molluscicidal composition comprising an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in together with an agrochemically acceptable diluent or carrier.9. A composition according to which further comprises one or more additional insecticidal claim 8 , acaricidal claim 8 , nematicidal or molluscicidal compounds.10. A method of protecting useful plants from insects claim 1 , acarines claim 1 , nematodes or molluscs claim 1 , comprising applying to said plants claim 1 , to the locus thereof claim 1 , or to plant propagation material thereof claim 1 , an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of ...

INSECTICIDAL COMPOUNDS

The present invention relates to novel triazole derivatives of formula (I) having insecticidal activity, to processes and intermediates for preparing them, toinsecticidal, acaricidal, nematicidal or molluscicidal compositions comprising them and to methods of using them to combat and control insect, acarine, nematode or mollusc pests (I) wherein X, X, X, Y, Y, R, R, Gand G, and Q are as described in formula 1 or salts and n-Oxides thereof. 3. A compound of formula (I) according to wherein{'sub': 1', '2, 'Yand Yare selected from Cl, Br, I, methyl, ethyl, methoxy, difluoromethoxy, and trifluoromethoxy,'}{'sub': '0', 'Xis hydrogen or Br or Cl'}{'sub': 1', '1', '2, 'Ris selected from hydrogen or C-Calkyl;'}{'sub': 2', '1', '2, 'Ris selected from hydrogen, C-Calkyl;'}{'sub': '1', 'Xis methoxy, fluorine or hydrogen;'}{'sup': 1', '2, 'Gand Gare both oxygen;'}4. A compound of formula (I) according to wherein{'sub': 1', '2, 'Yand Yare selected from Cl, Br, I, methyl, ethyl, methoxy, difluoromethoxy, and trifluoromethoxy,'}{'sub': '0', 'Xis hydrogen or Br or Cl'}{'sub': 1', '1', '2, 'Ris selected from hydrogen or C-Calkyl;'}{'sub': 2', '1', '2, 'Ris selected from hydrogen, C-Calkyl;'}{'sub': '1', 'Xis hydrogen;'}{'sub': '2', 'Xhydrogen, cyano, methoxy, halogen, or methyl;'}{'sup': 1', '2, 'Gand Gare both oxygen;'}6. A method of controlling insects claim 1 , acarines claim 1 , nematodes or molluscs which comprises applying to a pest claim 1 , to a locus of a pest claim 1 , or to a plant susceptible to attack by a pest an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in .7. An insecticidal claim 1 , acaricidal claim 1 , nematicidal or molluscicidal composition comprising an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in together with an agrochemically acceptable diluent or carrier.8. A ...

AMIDE DERIVATIVES, PROCESS FOR PREPARATION THEREOF AND USE THEREOF AS INSECTICIDE

An object of the present invention is to provide a compound represented by Formula (1): 114-. (canceled) The present invention relates to a compound represented by Formula (1):wherein A, A, Aand Aeach represent a carbon atom, a nitrogen atom or an oxidized nitrogen atom;Rand Reach represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted C1-C4 alkylcarbonyl group;Gand Geach represent an oxygen atom or a sulfur atom;X, which may be identical or different, represents a hydrogen atom, a halogen atom, a C1-C3 alkyl group or a trifluoromethyl group;n is an integer of 0 to 4; andQand Qeach represent an optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted heterocyclic group,an insecticide comprising the compound as the active ingredient, and a process for preparation thereof and use thereof.International Publication WO 2000/55120 and U.S. Pat. No. 6,548,514 describe a compound similar to the compound of the present invention for the use as medicament, but they do not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.International Publication WO 2000/7980 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.US Patent Laid-Open No. 2002-032238 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.The object of the present invention is to provide a pesticide having a high insecticidal efficacy. Another object of the present invention is to provide a compound represented by Formula (1), a process for ...

Substituted benzohydrazide analogs as histone demethylase inhibitors

Benzohydrazide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of lysine-specific histone demethylase, including LSD1 and LSD2; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the LSD1 and/or LSD2. 2. The compound of claim 1 , whereinX is CH andY is O.8. A pharmaceutical composition comprising a therapeutically effective amount of a compound of and a pharmaceutically acceptable carrier.9. A method for the treatment of a disorder of uncontrolled cellular proliferation in a mammal claim 1 , the method comprising the step of administering to the mammal an effective amount of a compound of .10. A method for decreasing histone demethylase activity in a mammal claim 1 , the method comprising the step of administering to the mammal an effective amount of a compound of .11. A method for inhibiting lysine specific demethylase 1 (LSD1) activity in a mammal claim 1 , the method comprising the step of administering to the mammal an effective amount of any of the compounds of the invention.13. The method of claim 12 , whereinX is CH andY is O. Over the past decade it has become clear that epigenetic changes, which alter gene activity without altering DNA sequence, collaborate with genetic mistakes to promote cancer development and progression (Tsai, H. C. and Baylin, S. B. 2011, 21 (3), 502-17; and Fullgrabe, J., Kavanagh, E., and Joseph, B. 2011). The regulation of the modifications on DNA and the proteins associated with DNA has become an area of intense interest and the enzymes involved in these processes have been suggested as a new class of protein targets for drug development. The major proteins associated with DNA are histone proteins. Histone tails are subject to a variety of posttranslational modifications, such as phosphorylation, acetylation, methylation, and ubiquitination, and ...

C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS

The present invention is directed to a compound represented by Structural Formula (A): 4. The compound of claim 3 , wherein Ris hydrogen or a (C-C)alkyl.5. The compound of claim 3 , wherein Ris selected from (C-C)alkyl claim 3 , (C-C)cycloalkyl(C-C)alkyl claim 3 , (C-C)alkoxy(C-C)alkyl claim 3 , phenyl claim 3 , phenyl(C-C)alkyl claim 3 , (C-C)cycloalkyl and halo(C-C)alkyl claim 3 , wherein each alkyl claim 3 , alkoxy and cycloalkyl moiety in the groups represented by Ris optionally substituted with one or more substituents independently selected from the group consisting of (C-C)alkyl and halo; and each phenyl moiety in the groups represented by Ris optionally substituted with one or more substituents independently selected from the group consisting of (C-C)alkyl claim 3 , halo claim 3 , (C-C)alkoxy claim 3 , (C-C)alkoxy(C-C)alkyl claim 3 , —CN claim 3 , halo(C-C)alkyl claim 3 , and halo(C-C)alkoxy.6. The compound of any one of claim 3 , wherein Ris selected from hydrogen claim 3 , methyl and ethyl.7. The compound of claim 6 , wherein Ris selected from the group consisting of cyclopropyl claim 6 , cyclobutyl claim 6 , cyclopentyl claim 6 , cyclopropylmethyl claim 6 , cyclobutylmethyl claim 6 , phenyl claim 6 , benzyl claim 6 , —(CH)—O—CH claim 6 , —(CH)—OCH claim 6 , —C(CH) claim 6 , —CH(CH) claim 6 , —CHC(CH) claim 6 , —CHCH(CH) claim 6 , —CH—CF claim 6 , —(CH)—CHF claim 6 , and —(CH)CH; n is 0 claim 6 , 1 claim 6 , 2 claim 6 , 3 claim 6 , 4 claim 6 , 5 or 6; and wherein the phenyl or benzyl group represented by Ris optionally substituted with one or two substituents independently selected from the group consisting of (C-C)alkyl claim 6 , halogen claim 6 , (C-C)alkoxy claim 6 , (C-C)alkoxy(C-C)alkyl claim 6 , —CN claim 6 , halo(C-C)alkyl claim 6 , and halo(C-C)alkoxy.8. The compound of claim 7 , wherein Ris selected from cyclopropyl claim 7 , cyclopropylmethyl claim 7 , cyclobutyl claim 7 , cyclopentyl claim 7 , cyclohexyl claim 7 , —(CH)—O—CH claim 7 , —C(CH) ...

PROLYL HYDROXYLASE INHIBITORS AND METHODS OF USE

The present disclosure relates to HIF-1α prolyl hydroxylase inhibitors, compositions which comprise the HIF-1α prolyl hydroxylase inhibitors described herein and to methods for controlling, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, and anemia. 3. The compound according to claim 2 , wherein Ris —OH.4. The compound according to claim 2 , wherein Ris —OCHor —OCHCH.5. The compound according to claim 2 , wherein Ris chosen from —NH claim 2 , —NHCH claim 2 , or —N(CH).6. The compound according to claim 2 , wherein Rand Rare both hydrogen.8. The compound according to claim 7 , wherein Ris —OH.9. The compound according to claim 7 , wherein Ris —OCHor —OCHCH.10. The compound according to claim 7 , wherein Ris chosen from —NH claim 7 , —NHCH claim 7 , or —N(CH).11. The compound according to claim 7 , wherein Rand Rare both hydrogen.13. The compound according to claim 12 , wherein Ris —OH.14. The compound according to claim 12 , wherein Ris —OCHor —OCHCH.15. The compound according to claim 12 , wherein Ris chosen from —NH claim 12 , —NHCH claim 12 , or —N(CH).16. The compound according to claim 12 , wherein Rand Rare both hydrogen.18. The compound according to claim 17 , wherein Ris —OH.19. The compound according to claim 17 , wherein Ris —OCHor —OCHCH.20. The compound according to claim 17 , wherein Ris chosen from —NH claim 17 , —NHCH claim 17 , or —N(CH).21. The compound according to claim 17 , wherein Rand Rare both hydrogen.23. The compound according to claim 22 , wherein Ris —OH.24. The compound according to claim 22 , wherein Ris —OCHor —OCHCH.25. The compound according to claim 22 , wherein Ris chosen from —NH claim 22 , —NHCH claim 22 , or —N(CH).26. The compound according to claim 22 , wherein Rand Rare both hydrogen.27. A compound chosen from:{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid;{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid methyl ester;{[5-(3- ...

PROCESSES FOR THE PREPARATION OF 4-ALKOXY-3-(ACYL OR ALKYL)OXYPICOLINAMDES

A fungicidal 4-methoxy-3-acetyloxypicolinamide may be conveniently prepared in processes that include the coupling together of 4-methoxy-3-acetyloxypicolinic acid or 4-methoxy-3-hydroxypicolinic acid with a key 2-aminopropanoate ester derived from a 1,1-bis(4-fluorophenyl)propane-1,2-diol. 2. The process of wherein the acylating agent is an alkyl chloroformate of the Formula ClCOR claim 1 , wherein R is a C-Calkyl or benzyl claim 1 , or an acid chloride of the Formula RCOCl claim 1 , wherein R is a C-Calkyl.3. The process of wherein the chlorinating agent is oxalyl chloride or thionyl chloride.4. The process of wherein the base may be selected from the group including triethylamine (TEA) claim 1 , diisopropylethylamine (DIPEA) claim 1 , pyridine claim 1 , potassium carbonate claim 1 , and mixtures thereof.5. The process of wherein the first mixture further comprises a solvent selected from the group including dichloromethane (DCM) claim 1 , 1 claim 1 ,2-dichloroethane (DCE) claim 1 , isopropyl acetate claim 1 , tetrahydrofuran (THF) claim 1 , 2-MeTHF claim 1 , acetonitrile (ACN) claim 1 , and mixtures thereof.7. The process of wherein the acylating agent is an alkyl chloroformate of the Formula ClCOR claim 6 , wherein R is a C-Calkyl or a benzyl.8. The process of wherein the first mixture further comprises a solvent selected from the group including dichloromethane (DCM) claim 6 , 1 claim 6 ,2-dichloroethane (DCE) claim 6 , acetonitrile (ACN) claim 6 , isopropyl acetate claim 6 , THF claim 6 , 2-MeTHF claim 6 , and mixtures thereof.9. The process of wherein the first base may be selected from the group including triethylamine (TEA) claim 6 , diisopropylethylamine (DIPEA) claim 6 , pyridine and potassium carbonate.10. The process of wherein about 3 equivalents of the first base and about 2 equivalents of the acylating agent are used.11. The process of wherein the alkali metal base may be selected from the group including LiOH claim 6 , NaOH claim 6 , KOH claim 6 , ...

PROCESSES FOR THE PREPARATION OF 4-ALKOXY-3-(ACYL OR ALKYL)OXYPICOLINAMDES

A fungicidal 4-methoxy-3-acetyloxypicolinamide may be conveniently prepared in processes that include the coupling together of 4-methoxy-3-acetyloxypicolinic acid or 4-methoxy-3-hydroxypicolinic acid with a key 2-aminopropanoate ester derived from a 1,1-bis(4-fluorophenyl)propane-1,2-diol. 1. A compound selected from the group consisting of:{'sub': 1', '1', '4', '2, 'wherein Ris a C-Calkyl or PhCH; and'} The present disclosure concerns processes for the preparation of 4-alkoxy-3-(acyl or alkyl)oxypicolinamides. More particularly, the present disclosure concerns a process for the preparation of 4-methoxy-3-(acetyl or acetyloxymethyl)oxypicolinamides from 4-methoxy-3-hydroxypicolinic acids or 4-methoxy-3-acetyloxypicolinic acids.U.S. patent applications Ser. Nos. 15/036,314 and 15/036,316 describes inter alia certain heterocyclic aromatic amide compounds of general Formulaand their use as fungicides. It would be useful to have an efficient and scalable process route to these heterocyclic aromatic amide compounds from inexpensive raw materials.The present disclosure concerns processes for the preparation of the 4-methoxy-3-(acetyl or acetyloxymethyl)oxypicolinamides of Formula Awherein Y is CHCO or CHCOOCH;from the compounds of Formulas B or DThe compound of Formula A, wherein Y is CHCO, may be prepared in a process that comprises the following steps:The compound of Formula A, wherein Y is CHCO or CHCOOCH, may be prepared in a process that comprises the following steps:an acylating agent, and a base;The compound of Formula Can acylating agent and a base;to the first mixture to form a second mixture;from the second mixture;The compound of Formula C may also be prepared in a process that comprises the following steps:an acylating agent and a base;Another aspect of the present disclosure are the novel intermediates produced in the present process, viz., the compounds:wherein Ris a C-Calkyl or PhCH; andwherein X is Cl, Br, HSO, HPOor CHSO.The term “alkyl” refers to a ...

Amide derivatives as lysophosphatidic acid receptor antagonists

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, formula (I) wherein R, X, m, R, Y, R, Z, n, R, A and B are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy. 118.-. (canceled)19. A method of treating a condition whose development or symptoms are linked to LPAR5 activity comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound selected from 4-((N-(cyclopropylmethyl)-2-fluoro-4-(2-fluorophenoxy)benzamido)methyl)benzoic acid , 4-((N-(cyclopropylmethyl)-4-(2-fluorophenoxy)benzamido)methyl)benzoic acid , 4-((N-(cyclopropylmethyl)-4-(2-methoxyphenoxy)benzamido)methyl)benzoic acid , and a pharmaceutically acceptable salt of any of the foregoing.20. The method according to claim 19 , wherein the condition is chosen from fibrosis claim 19 , liver diseases claim 19 , atherosclerosis claim 19 , inflammatory diseases claim 19 , gastrointestinal tract diseases claim 19 , and pain disorders.21. The method according to claim 19 , wherein the compound is 4-((N-(cyclopropylmethyl)-2-fluoro-4-(2-fluorophenoxy)benzamido)methyl)benzoic acid.22. The method according to claim 19 , wherein the compound is 4-((N-(cyclopropylmethyl)-2-fluoro-4-(2-fluorophenoxy)benzamido)methyl)benzoic acid or a pharmaceutically acceptable salt thereof.23. The method according to claim 19 , wherein the compound is 4-((N-(cyclopropylmethyl)-4-(2-fluorophenoxy)benzamido)methyl)benzoic acid.24. The method according to claim 19 , wherein the compound is 4-((N-(cyclopropylmethyl)-4-(2-fluorophenoxy)benzamido)methyl)benzoic acid or a pharmaceutically acceptable salt thereof.25. The method according to claim 19 , wherein the compound is 4-((N-(cyclopropylmethyl)-4-(2-methoxyphenoxy)benzamido)methyl)benzoic acid.26. The method according to claim 19 , wherein the compound is 4-((N-(cyclopropylmethyl)-4-(2-methoxyphenoxy)benzamido) ...

ANTIBACTERIAL AGENTS

Antibacterial compounds of formula (I) are provided: 2. A compound according to claim 1 , wherein A is substituted C-Calkyl claim 1 , wherein at least one substituent is hydroxy.3. A compound according to claim 2 , wherein A is substituted C-Calkyl claim 2 , wherein at least two substituents are hydroxy.4. A compound according to claim 2 , wherein A is hydroxymethyl claim 2 , hydroxyethyl claim 2 , hydroxypropyl or dihydroxpropyl.5. A compound according to claim 1 , wherein A is substituted C-Ccycloalkyl claim 1 , wherein at least one substituent is selected from hydroxy and hydroxyalkyl.6. A compound according to claim 5 , wherein A is substituted C-Ccycloalkyl claim 5 , wherein at least one substituent is hydroxymethyl.7. A compound according to claim 6 , wherein A is hydroxymethylcyclopropyl.8. A compound according to claim 5 , wherein A is substituted C-Ccycloalkyl claim 5 , wherein at least one substituent is hydroxy.9. A compound according to claim 1 , wherein G is —C≡C—C≡C—.1012-. (canceled)14. A compound according to claim 13 , wherein Ris hydrogen.15. A compound according to claim 13 , wherein Ris hydrogen.16. A compound according to claim 13 , wherein E is —C(CH)SCH.17. A compound according to claim 13 , wherein E is —C(CH)S(O)CH.18. A compound according to claim 13 , wherein E is —C(CH)S(O)CH.19. (canceled)20. A compound selected from the group consisting of:N-hydroxy-2-(4-(((trans)-2-(hydroxymethyl)cyclopropyl)buta-1,3-diynyl)phenyl)-1,6-naphthyridine-4-carboxamide (Compound 1);N—((R)-1-(hydroxyamino)-3-methyl-3-(methylthio)-1-oxobutan-2-yl)-4-(((trans)-2-(hydroxymethyl)cyclopropyl)buta-1,3-diynyl)benzamide (Compound 2);N-((2R)-1-(hydroxyamino)-3-methyl-3-(methylsulfinyl)-1-oxobutan-2-yl)-4-(((trans)-2-(hydroxymethyl)cyclopropyl)buta-1,3-diynyl)benzamide (Compound 3);N-((2R)-1-(hydroxyamino)-3-methyl-3-(methylsulfinyl)-1-oxobutan-2-yl)-4-(((trans)-2-(hydroxymethyl)cyclopropyl)buta-1,3-diynyl)benzamide (Compound 4);N—((R)-1-(hydroxyamino)-3-methyl-3-( ...

GOLD COMPLEXES

Gold (I) hydroxide complexes of the form Z—Au—OH and digold complexes of the form Z—Au-(μOH)—Au—Z where groups Z are two electron donors are provided. The groups Z may be carbenes, for example nitrogen containing heterocyclic carbenes (NHCs), phosphines or phosphites. The complexes can be used as catalysts, for example in reactions such as hydration of nitriles, skeletal arrangement of enynes, alkoxycyclisation of enynes, alkyne hydration, the Meyer-Shuster reaction, 3,3′ rearrangement of allylic acetates, cyclisation of propargylic acetates, Beckman rearrangements and hydroamination. The complexes can be used in medicine, for example in the treatment of cancer. 2. The method according to wherein the complex is used as a catalyst claim 1 , or for the in situ production of a catalyst claim 1 , for catalyzing a chemical transformation of the substrate claim 1 , the chemical transformation selected from the group consisting of: hydration of nitriles claim 1 , skeletal arrangement of enynes claim 1 , alkoxycyclisation of enynes claim 1 , alkyne hydration claim 1 , the Meyer-Shuster reaction claim 1 , 3 claim 1 ,3′ rearrangement of allylic acetates claim 1 , cyclisation of propargylic acetates claim 1 , Beckman rearrangements and hydroamination.3. (canceled)4. (canceled)5. The method according to wherein the complex is according to general formula V and the anion A is selected from the group consisting of BF claim 1 , PF claim 1 , SbF claim 1 , [B{CH(CF)}] claim 1 , and [B(CF)].6. The method according to wherein the groups Z are selected from the group consisting of carbene claim 1 , phosphine claim 1 , and phosphite two-electron donor ligands.7. The method according to wherein the groups Z are selected from the group consisting of cyclic or acyclic carbenes having one or more heteroatoms claim 6 , triphenylphosphine claim 6 , substituted triphenylphenylphosphine claim 6 , substituted triphenylphosphite claim 6 , and substituted triphenyl phosphite.8. The method ...

CYCLIC PROTEIN TYROSINE KINASE INHIBITORS

Novel cyclic compounds and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders. 2. A compound of claim 1 , wherein Ris hydrogen.3. A compound of claim 1 , wherein Ris hydrogen.4. A compound of claim 1 , wherein Ris hydrogen.69. A compound of claim claim 1 , wherein Ris aryl which is unsubstituted or independently substituted with one or more alkyl or halo.7. A pharmaceutical composition claim 1 , comprising a pharmaceutically acceptable vehicle ordiluent and at least one compound of .8. A pharmaceutical composition claim 8 , comprising a pharmaceutically acceptable vehicle ordiluent and at least one compound of . This application is a continuation of Ser. No. 15/163,750 filed May 25, 2016, now allowed, which is a continuation of Ser. No. 14/620,244, filed Feb. 12, 2015, now U.S. Pat. No. 9,382,219, which is a continuation of Ser. No. 14/226,868, filed Mar. 27, 2014, now U.S. Pat. No. 8,993,567, which is a continuation of Ser. No. 11/271,626, filed Nov. 10, 2005, now U.S. Pat. No. 8,716,323, which is a continuation of application Ser. No. 10/378,373 filed Mar. 3, 2003, which is a continuation of application Ser. No. 09/548,929 filed Apr. 13, 2000, now U.S. Pat. No. 6,596,746, which claims priority from provisional application No. 60/129,510 filed Apr. 15, 1999. The entire disclosure of each of the foregoing applications is herein incorporated by reference in its entirety.The present invention relates to cyclic compounds and salts thereof, to methods of using such compounds in treating protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders, and to pharmaceutical compositions containing such compounds.Protein tyrosine kinases (PTKs) are enzymes which, in conjuction with ATP as a substrate, phosphorylate tyrosine residues in peptides and proteins. These enzymes are key ...

AMIDE DERIVATIVES AS NAV1.7 AND NAV1.8 BLOCKERS

The present invention relates to amide derivatives which have blocking activities of voltage gated sodium channels as the Nav1.7 and Nav1.8 channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved. 2. The compound described in wherein:A is phenyl, pyridyl, pyrazyl, pyrimidyl, quinolyl, isoquinolyl, quinoxalyl, or naphthyl;{'sup': 8a', '8b', '8a', '8b', '9', '9', '8a', '8b, 'X is selected from the group consisting of: —CRR—, —O—, —O—CRR—, —NR—, —NR—CRR—, and —S—;'}{'sup': 5a', '5c, 'Rand Rare independently selected from the group consisting of{'sub': 1-6', '1-6, '(1) hydrogen, (2) halogen, (3) hydroxyl, and (4) Calkyl, wherein the Calkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting ofhalogen and hydroxyl;{'sup': '5b', 'Ris hydrogen;'}{'sup': '5d', 'sub': '1-6', 'Ris selected from the group consisting of: (1) hydrogen, (2) halogen, and (3) Calkyl;'}{'sup': 5c', '5d, 'sub': '3-6', 'Rmay form a Ccycloalkyl with R;'}or a prodrug thereof or a pharmaceutically acceptable salt thereof.5. The compound described in wherein:W is N;or a prodrug thereof or a pharmaceutically acceptable salt thereof.6. The compound described in claim 1 , which is selected from the group consisting of:2-(cyclopropanecarboxamido)-N-(2-(4-(trifluoromethyl)phenoxy)propyl)isonicotinamide;2-acetamido-N-(2-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)amino)ethyl)isonicotinamide;N-(2-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)amino)ethyl)-2-propionamidoisonicotinamide;2-acetamido-N-(2-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)amino)ethyl)-6-methylisonicotinamide;N-(2-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)amino)ethyl)-2- ...

CARBOXAMIDES AS MODULATORS OF SODIUM CHANNELS

Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain. 1. (canceled)316-. (canceled)17. The compound of claim 2 , wherein the compound is selected from the group of compounds identified in Tables 1 claim 2 , 1A claim 2 , and 1B claim 2 , or a pharmaceutically acceptable salt thereof.18. The compound of .19. (canceled)20. A pharmaceutical composition comprising the compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , and one or more pharmaceutically acceptable carriers or vehicles.21. A method of inhibiting a voltage-gated sodium channel in a subject comprising administering to the subject the compound of claim 2 , or a pharmaceutically acceptable salt thereof.22. (canceled)23. A method of treating or lessening the severity in a subject of chronic pain claim 2 , gut pain claim 2 , neuropathic pain claim 2 , musculoskeletal pain claim 2 , acute pain claim 2 , inflammatory pain claim 2 , cancer pain claim 2 , idiopathic pain claim 2 , postsurgical pain claim 2 , visceral pain claim 2 , multiple sclerosis claim 2 , Charcot-Marie-Tooth syndrome claim 2 , incontinence claim 2 , pathological cough claim 2 , or cardiac arrhythmia comprising administering to the subject an effective amount of the compound of claim 2 , or a pharmaceutically acceptable salt thereof.2434-. (canceled)35. The method of claim 23 , wherein said subject is treated with one or more additional therapeutic agents administered concurrently with claim 23 , prior to claim 23 , or subsequent to treatment with the compound or pharmaceutically acceptable salt.3752-. (canceled)53. The compound of claim 36 , wherein the compound is selected from the group of compounds ...

Novel co-crystals

The disclosure provides new, stable, pharmaceutically acceptable co-crystal forms of 1-(4-fluoro-phenyl)-4-((6bR, 10aS)-3-methyl-2,3,6b,9, 10, 10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de[quinoxalin-8-yl)-butan-1-one, together with methods of making and using them, and pharmaceutical compositions comprising them.

PROCESSES FOR PREPARING TOLL-LIKE RECEPTOR MODULATOR COMPOUNDS

The present disclosure provides methods for preparing (R)-2-((2-amino-7-fluoropyrido[3,2-d]pyrimidin-4-yl)amino)-2-methylhexan-1-ol or a salt thereof and related key intermediates. 3. The method of claim 1 , wherein the salt of the compound having the Formula PG-NHC(═NH)NHis a hemisulfate claim 1 , a sulfate claim 1 , a chloride claim 1 , a bromide claim 1 , a carbonate claim 1 , a nitrate claim 1 , or an acetate salt.4. The method of claim 1 , wherein PG is 2 claim 1 ,4-dimethoxybenzyl.5. The method of claim 2 , wherein the first transition-metal catalyst comprises a copper metal claim 2 , a copper oxide claim 2 , a copper (I) salt claim 2 , a copper (II) salt claim 2 , or combinations thereof.6. The method of claim 2 , wherein the first transition-metal catalyst is Cu(I) iodide claim 2 , Cu(I) bromide claim 2 , Cu(I) chloride claim 2 , Cu(I) acetate claim 2 , Cu(I) carbonate claim 2 , Cu(I) nitrate claim 2 , Cu(I) sulfate claim 2 , Cu(I) phosphate claim 2 , Cu(I) 3-methylsalicylate claim 2 , Cu(I) thiophene-2-carboxylate claim 2 , Cu(I) oxide claim 2 , Cu(II) iodide claim 2 , Cu(II) bromide claim 2 , Cu(II) chloride claim 2 , Cu(II) acetate claim 2 , Cu(II) carbonate claim 2 , Cu(II) nitrate claim 2 , Cu(II) sulfate claim 2 , Cu(II) pyrophosphate claim 2 , Cu(II) phosphate claim 2 , Cu(II) tartrate claim 2 , Cu(II) oxide claim 2 , or combinations thereof.7. The method of claim 2 , wherein the first transition-metal catalyst comprises Cu(II) acetate.8. The method of claim 1 , wherein the first base is lithium carbonate claim 1 , sodium carbonate claim 1 , potassium carbonate claim 1 , cesium carbonate claim 1 , lithium bicarbonate claim 1 , sodium bicarbonate claim 1 , potassium bicarbonate claim 1 , sodium phosphate tribasic claim 1 , potassium phosphate tribasic claim 1 , potassium acetate claim 1 , potassium trimethylacetate claim 1 , tetrabutylphosphonium malonate claim 1 , 1 claim 1 ,8-diazabicyclo[5.4.0]undec-7-ene claim 1 , 1 claim 1 ,5-diazabicyclo[4.3.0] ...

SOLID FORMS OF {[5-(3-CHLOROPHENYL)-3-HYDROXYPYRIDINE-2-CARBONYL]AMINO}ACETIC ACID, COMPOSITIONS, AND USES THEREOF

Provided herein are solid forms comprising {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino} acetic acid, compositions comprising the solid forms, methods of making the solid forms and methods of their use for the treatment of various diseases and/or disorders. 132.-. (canceled)34. The crystalline Compound (I) of claim 33 , which has an X-ray powder diffraction pattern as shown in .35. The crystalline Compound (I) of claim 33 , which has a DSC endotherm at about 176.2° C.36. The crystalline Compound (I) of claim 33 , wherein the crystalline Compound (I) comprises less than 10% by weight of any other crystalline Compound (I).37. The crystalline Compound (I) of claim 36 , wherein the crystalline Compound (I) comprises less than 5% by weight of any other crystalline Compound (I).38. The crystalline Compound (I) of claim 33 , wherein the crystalline Compound (I) comprises less than 10% by weight of amorphous Compound (I).39. The crystalline Compound (I) of claim 38 , wherein the crystalline Compound (I) comprises less than 5% by weight of amorphous Compound (I).41. The crystalline Compound (I) of claim 40 , wherein the crystalline Compound (I) comprises less than 50 ppm of a compound of Formula (II) as determined by GC/MS.42. The crystalline Compound (I) of claim 33 , wherein the crystalline Compound (I) is at least 99.5% pure as measured by HPLC.43. A pharmaceutical composition comprising a crystalline Compound (I) of .44. A method of treating anemia claim 33 , comprising administering a pharmaceutical composition comprising an effective amount of a crystalline Compound (I) of .46. The crystalline Compound (I) of claim 45 , which has an X-ray powder diffraction pattern as shown in .47. The crystalline Compound (I) of claim 45 , wherein the crystalline Compound (I) comprises less than 10% by weight of any other crystalline Compound (I).48. The crystalline Compound (I) of claim 47 , wherein the crystalline Compound (I) comprises less than 5% by weight of any other ...

FUSED HETEROARYL PYRIDYL AND PHENYL BENZENESUFLONAMIDES AS CCR2 MODULATORS FOR THE TREATMENT OF INFLAMMATION

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists. 123-. (canceled)25. The method of claim 24 , wherein the compound of Formula B is reacted with NaOH and chloromethyl methyl ether to produce the compound of Formula C.27. The method of claim 26 , wherein the reaction is conducted in presence of N claim 26 ,N′-carbonyldiimidazole.29. The method of claim 28 , further comprising reacting 3-amino-5-methylpicolino-nitrile with 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride in pyridine to form the compound of Formula E.30. The method of claim 24 , wherein the solvent used to produce the Grignard reagent is tetrahydrofuran.31. The method of claim 24 , wherein the solvent used in step (b) is tetrahydrofuran.32. The method of claim 24 , wherein step (c) is conducted with an acid.33. The method of claim 32 , wherein the acid is hydrochloric acid.40. The method of claim 39 , wherein the Grignard reagent is formed by reacting 4-iodo-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2 claim 39 ,3-d]pyrimidine with isopropylmagnesium chloride.41. The method of claim 39 , wherein the acid is hydrochloric acid.42. The method of claim 39 , wherein the intermediate D is reacted with O claim 39 , N-dimethyl-hydroxylamine hydrochloride in the presence of N claim 39 ,N′-carbonyldiimidazole. This application is a continuation of U.S. Ser. No. 12/171,782, filed Jul. 11, 2008, which application claims priority to U.S. provisional application Ser. No. 60/949,328, filed Jul. 12, 2007. The disclosures of these priority applications are incorporated by reference herein in their entirety.The present invention described herein was supported at least in part by NIH (U19-AI056690-01). The government has certain rights in the invention.The present ...

SUBSTITUTED PYRIDYL AMIDE COMPOUNDS AS MODULATORS OF THE HISTAMINE H3 RECEPTOR

Certain substituted pyridyl amide compounds are histamine Hreceptor modulators useful in the treatment of histamine Hreceptor-mediated diseases. 2. A compound as defined in claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , sec-butyl claim 1 , or tert-butyl.3. A compound as defined in claim 1 , wherein Ris methyl or isopropyl.4. A compound as defined in claim 1 , wherein Ris cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , or cyclohexyl.5. A compound as defined in claim 1 , wherein m is 1.6. A compound as defined in claim 1 , wherein m is 2.7. A compound as defined in claim 1 , wherein X is N claim 1 , Y is CR claim 1 , and Ris —Z—Ar.8. A compound as defined in claim 1 , wherein X is CH claim 1 , Y is N claim 1 , and Ris —Z—Ar.9. A compound as defined in claim 1 , wherein X is N claim 1 , Y is CR claim 1 , and Ris —H claim 1 , where Ris —Z—Ar.10. A compound as defined in claim 1 , wherein Ris —CN claim 1 , —CONH claim 1 , or —CHNH.11. A compound as defined in claim 1 , wherein Ris —H.12. A compound as defined in claim 1 , wherein Z is O.13. A compound as defined in claim 1 , wherein Z is S.14. A compound as defined in claim 1 , wherein Ar is a phenyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , thiophenyl claim 1 , imidazolyl claim 1 , pyrazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , thiazolyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , or pyrazinyl group claim 1 , each unsubstituted or substituted with one claim 1 , two claim 1 , or three Rsubstituents.15. A compound as defined in claim 1 , wherein Ar is a phenyl group unsubstituted or substituted with one claim 1 , two claim 1 , or three Rsubstituents.16. A compound as defined in claim 1 , wherein Ar is a 4-halophenyl group.17. A compound as defined in claim 1 , wherein Ar is phenyl claim 1 , 3 claim 1 ,4-dichlorophenyl claim 1 , 4-methylsulfanylphenyl claim 1 , 3-chlorophenyl claim 1 , 3-fluorophenyl claim 1 , 4-chloro-3- ...

HISTONE DEACETYLASE INHIBITORS AND METHODS OF USE THEREOF

The present invention provides novel compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of a compound of the invention to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention. 2. The compound of claim 1 , wherein Rand Rare each H.3. The compound of claim 1 , wherein Ar is a substituted or unsubstituted carbocyclic aryl group having from 6 to 10 atoms in the rings system.4. The compound of claim 1 , wherein Ar is substituted or unsubstituted phenyl.5. The compound of claim 1 , wherein Ar is phenyl substituted L at the position on the phenyl ring para to the —(CRR)—Z moiety.6. The compound of claim 1 , wherein L is a linker having 1-6 atoms.7. The compound of claim 6 , wherein the linker comprises an alkylidene claim 6 , an ether claim 6 , a thioether claim 6 , an amine claim 6 , an amide claim 6 , an ester claim 6 , a carbonate claim 6 , a carbamate claim 6 , or a hydrazone.8. The compound of claim 7 , wherein the linker comprises —(CH)—O— claim 7 , wherein m is an integer from 1 to 4.9. The compound of claim 1 , wherein CAP is a substituted or unsubstituted aryl group.10. The compound of claim 9 , wherein CAP is a substituted or unsubstituted phenyl group.11. The compound of claim 10 , wherein the phenyl group is substituted with 1-5 electron-withdrawing substituents.12. The compound of claim 11 , wherein the 1-5 electron-withdrawing substituents are 1-5 fluorine atoms.13. The compound of claim 1 , wherein Z is —C(O)NHOH.14. The compound of claim 1 , where in n is 1.15. The compound of claim 1 , wherein n is 2 or 3.18. The compound of claim 17 , wherein Ar is a substituted phenyl ...

METHODS FOR SYNTHESIS OF OXYPICOLINAMIDES

The present technology relates to processes, mixtures and intermediates useful for making fungicide, florylpicoxamid. Also disclosed herein are processes for addition reactions which suppress epimerization and/or racemization. 2. The process of wherein Pis hydrogen and Pis Pg claim 1 , where Pg is Calkoxycarbonyl or substituted Calkoxycarbonyl.4. The process of wherein Pis hydrogen and Pis Pg claim 1 , where Pg is tosyl (Ts).5. The process of wherein Pis hydrogen and Pis Pg claim 1 , where Pg is nosyl (Ns).6. The process of wherein Pis hydrogen and Pis Pg claim 1 , where Pg is silyl.11. The process of any one of - wherein the amount of acylation catalyst is from 0.5-20 mol % based on the amount of compound III.12. The process of any one of - wherein the mixing occurs under conditions further comprising an aprotic organic solvent.13. The process of wherein the solvent is heptanes.14. The process of any one of - wherein the mixing occurs under conditions further comprising heating the mixture to about 65° C.16. The process of any one of - wherein compound I is in 99% de.17. A mixture comprising two or more compounds of formula I; wherein one compound is in 97% de.18. A mixture comprising two or more compounds of formula I; wherein one compound is in 98% de.19. A mixture comprising two or more compounds of formula I; wherein one compound is in 99% de.20. A mixture comprising two or more compounds of formula I; wherein one compound is in 99.5% de. This is a national phase entry under 35 U.S.C § 371 of international patent application PCT/US19/55771, filed on Oct. 11, 2019 and published in English as international patent publication WO 2020/081382, which claims priority to the benefit of U.S. Provisional Patent Application Ser. No. 62/745,684 filed Oct. 15, 2018, the disclosure of which is hereby incorporated by reference in its entirety.Particular small molecules of the 4-methoxy-3-(acetyl or acetyloxymethyl) oxypicolinamide persuasion are of interest as being ...

PSMA Imaging Agents

Compounds for targeting and agents for imaging, prostate-specific membrane antigen (PSMA) are disclosed. Methods of synthesizing compounds and imaging agents, as well as methods for imaging PSMA are also disclosed. The imaging agents disclosed are suitable for PET and SPECT imaging. 2. The compound of claim 1 , wherein in Formula VI claim 1 , Xis N.3. The compound of claim 1 , wherein in Formula VI claim 1 , Xis H and Xis (CH)—Rwherein at least one CHof (CH)is replaced by CONH.4. The compound of claim 1 , wherein in Formula VI claim 1 , Xis H and Xis (CH)—Rwherein at least one CHof (CH)is replaced by CONH.5. The compound of claim 1 , wherein in Formula VI claim 1 , at least one CHof (CH)—Rof either Xor Xis replaced by triazole.6. The compound of claim 1 , wherein in Formula VI claim 1 , Ris a radioisotope.8. The compound of claim 7 , wherein in Formula VIII claim 7 , Xis CH.9. The compound of claim 7 , wherein in Formula VIII claim 7 , Xis CH.10. The compound of claim 7 , wherein in Formula VIII claim 7 , at least one CHof (CH)is optionally replaced by O.11. The compound of claim 7 , wherein in Formula VIII claim 7 , Xis N.12. The compound of claim 7 , wherein in Formula VIII claim 7 , Xis CH.14. The method of claim 13 , wherein in Formula VI claim 13 , Xis N.15. The method of claim 13 , wherein in Formula VI claim 13 , Xis H and Xis (CH)—Rwherein at least one CHof (CH)is replaced by CONH.16. The method of claim 13 , wherein in Formula VI claim 13 , Xis H and Xis (CH)—Rwherein at least one CHof (CH)is replaced by CONH.17. The method of claim 13 , wherein in Formula VI claim 13 , at least one CHof (CH)—Rof either Xor Xis replaced by triazole.18. The method of claim 13 , wherein in Formula VI claim 13 , Ris a radioisotope.19. The method of claim 13 , wherein in Formula VIII claim 13 , Xis CH.20. The method of claim 13 , wherein in Formula VIII claim 13 , Xis CH.21. The method of claim 13 , wherein in Formula VIII claim 13 , at least one CHof (CH)is optionally replaced ...

INSECTICIDAL COMPOUNDS

The present invention relates to novel triazole derivatives of formula (I) having insecticidal activity, to processes and intermediates for preparing them, to insecticidal, acaricidal, nematicidal or molluscicidal compositions comprising them and to methods of using them to combat and control insect, acarine, nematode or mollusc pests wherein R, R, G, G, Qand Qare as defined in claim ; or salts thereof. 2. A compound of formula (I) according to characterized in that{'sup': '1', 'Qis 4-pyridyl or 1-oxidopyridin-1-ium-4-yl;'}{'sup': '1', 'Yis selected from Cl, Br, I, methyl, ethyl, methoxy, difluoromethoxy, trifluoromethoxy, or methoxymethyl'}{'sup': '5', 'Yis selected from Cl, Br, I, ethyl'}{'sup': '3', 'Yis heptafluoroprop-2-yl or nonafluorobut-2-yl'}X is hydrogen or F{'sup': '1', 'sub': 1', '8', '2', '8, 'Ris selected from C-Calkyl, C-Calkenyl;'}{'sup': '2', 'sub': 1', '8', '2', '8, 'Ris selected from hydrogen, C-Calkyl, C-Calkenyl; and'}{'sup': 1', '2, 'Gand Gare both oxygen;'}3. A compound of formula (I) according to characterized in that{'sup': '1', 'Qis 4-pyridyl or 1-oxidopyridin-1-ium-4-yl;'}{'sup': '1', 'Yis selected from Cl, Br, I, methyl, ethyl;'}{'sup': '5', 'Yis selected from Cl, Br, I, ethyl;'}{'sup': '3', 'Yis heptafluoroprop-2-yl'}X is hydrogen or F{'sup': '1', 'sub': 2', '4, 'Ris selected from C-Calkyl;'}{'sup': '2', 'sub': 1', '4, 'Ris selected from hydrogen, C-Calkyl; and'}{'sup': 1', '2, 'Gand Gare both oxygen;'}4. A compound of formula (I) according to characterized in that{'sup': '1', 'Qis 4-pyridyl or 1-oxidopyridin-1-ium-4-yl;'}{'sup': '1', 'Yis selected from Cl, Br, methyl, ethyl;'}{'sup': '5', 'Yis selected from Cl, Br, ethyl;'}{'sup': '3', 'Yis heptafluoroprop-2-yl'}X is hydrogen or F{'sup': '1', 'sub': 2', '4, 'Ris selected from C-Calkyl;'}{'sup': '2', 'sub': 1', '4, 'Ris selected from hydrogen, C-Calkyl; and'}{'sup': 1', '2, 'Gand Gare both oxygen;'}5. A compound of formula (I) according to characterized in that{'sup': '1', 'Qis 4-pyridyl ...

FATTY ACID NIACIN CONJUGATES AND THEIR USES

The invention relates to fatty acid niacin conjugates; compositions comprising an effective amount of a fatty acid niacin conjugate; and methods for treating or preventing an metabolic disease comprising the administration of an effective amount of a fatty acid niacin conjugate. 3. The method of claim 2 , wherein t is 1.4. The method of claim 3 , wherein r is 2 and s is 6.5. The method of claim 3 , wherein r is 3 and s is 5.6. The method of claim 3 , wherein r is 7 and s is 3.7. The method of claim 4 , wherein L is —S—S—.8. The method of claim 4 , wherein L is —O—.13. The method of claim 4 , wherein one of n claim 4 , o claim 4 , p claim 4 , and q are each 1.14. The method of claim 4 , wherein two of n claim 4 , o claim 4 , p claim 4 , and q are each 1.15. The method of claim 4 , wherein m is 1 claim 4 , n claim 4 , o claim 4 , p claim 4 , and q are each 1 claim 4 , and L is O.15. The method of claim 4 , wherein m is 1 claim 4 , n claim 4 , o claim 4 , p claim 4 , and q are each 1 claim 4 , and L is —S—S—.17. The method of claim 4 , wherein m claim 4 , n claim 4 , and o are each 0 claim 4 , and p and q are each 1.21. The method of claim 4 , wherein m is 1 claim 4 , n claim 4 , o claim 4 , p claim 4 , and q are each 1 claim 4 , and L is NR.22. The method of claim 4 , wherein m claim 4 , n claim 4 , and o are each 0 claim 4 , and p and q are each 1 claim 4 , and one c is —CHand the other c is —CH. This application is a continuation of U.S. Non-Provisional application Ser. No. 13/451,217, which claims the benefit of U.S. Provisional Application No. 61/478,091 filed Apr. 22, 2011, and which is a continuation-in-part of U.S. Non-Provisional application Ser. No. 12/872,555 filed Aug. 31, 2010, now U.S. Pat. No. 8,304,551, which claims priority to U.S. Provisional Application No. 61/238,903, filed Sep. 1, 2009, U.S. Provisional Application No. 61/308,524, filed Feb. 26, 2010, and U.S. Provisional Application No. 61/310,952, filed Mar. 5, 2010. The entire disclosures of ...

PSMA Imaging Agents

Compounds for targeting and agents for imaging, prostate-specific membrane antigen (PSMA) are disclosed. Methods of synthesizing compounds and imaging agents, as well as methods for imaging PSMA are also disclosed. The imaging agents disclosed are suitable for PET and SPECT imaging. 2. The method of claim 1 , wherein in Formula IV claim 1 , Xis NH.4. The method of claim 1 , wherein in Formula IV claim 1 , Xis an aryl.6. The method of claim 1 , wherein in Formula IV claim 1 , Xis a single bond.7. The method of claim 1 , wherein in Formula IV claim 1 , Ris a radioisotope.8. The method of claim 1 , wherein in Formula IV claim 1 , Xis C(O) and Xis a sugar.9. The method of claim 1 , wherein in Formula V claim 1 , Xis CH.10. The method of claim 1 , wherein in Formula V claim 1 , Xis N.11. The method of claim 1 , wherein in Formula V claim 1 , Xis CH.12. The method of claim 1 , wherein in Formula V claim 1 , Xis N.13. The method of claim 1 , wherein in Formula V claim 1 , wherein one CHis replaced by an aryl.14. The method of claim 1 , wherein Ris O.15. The method of claim 1 , wherein Ris S.17. The compound of claim 16 , wherein in Formula IV claim 16 , Xis NH.19. The compound of claim 16 , wherein in Formula IV claim 16 , Xis an aryl.21. The compound of claim 16 , wherein in Formula IV claim 16 , Xis a single bond.22. The compound of claim 16 , wherein in Formula IV claim 16 , Ris a radioisotope.23. The compound of claim 16 , wherein in Formula IV claim 16 , Xis C(O) and Xis a sugar.26. The compound of claim 25 , wherein in Formula V claim 25 , Xis CH.27. The compound of claim 25 , wherein in Formula V claim 25 , Xis N.28. The compound of claim 25 , wherein in Formula V claim 25 , Xis CH.29. The compound of claim 25 , wherein in Formula V claim 25 , Xis N.30. The compound of claim 25 , wherein in Formula V claim 25 , wherein one CHis replaced by an aryl.31. The compound of claim 25 , wherein Ris O.32. The compound of claim 25 , wherein Ris S. This Continuation application ...

PROCESS FOR PREPARING N-METHYL-4-BENZYLCARBAMIDOPYRIDINIUM CHLORIDE

The present application relates to a new salt of N-methyl-4-benzylcarbami-dopyridine, a process for its preparation, a pharmaceutical composition comprising this compound and its use for the treatment or prevention of viral diseases. 2. The process according to wherein a solvent selected from the group consisting of 2-propanol claim 1 , aqueous ethanol and acetonitrile is used.3. The process of wherein the process is carried out at a temperature in the range of 50-120° C. and under pressure.4. The process according to wherein the reaction is carried out in acetonitrile with heating and permanent passing of chloromethane gas through the reaction mixture without any pressure application.5. The process of wherein the reaction time is in the range from 1-20 h.6. The process according to wherein the molar ratio between isonicotinic acid benzylamide and chloromethane is in the range of 1-1.5.7. The process according to wherein the solvent is ethanol 96% claim 2 , wherein the reaction is carried out at a pressure in the range of 0.1-1 MPa (1-10 bar) and wherein the molar ratio between isonicotinic acid benzylamide and chloromethane is in the range of 1-1.5.8. The process according to claim 1 , further comprising the step of recrystallisation of the raw product from ethanol 96%.917-. (canceled)18. The process of wherein the N-methyl-4-benzylcarbamidopyridinium chloride comprises impurities in the range of less than 0.5%.19. The process of wherein the N-methyl-4-benzylcarbamidopyridinium chloride comprises impurities in the range of less than 0.05%.20. The process of wherein the N-methyl-4-benzylcarbamidopyridinium has a melting temperature in the range of 198° C. to 203° C. The present invention relates to a process for the preparation of N-methyl-4-benzylcarbamidopyridinium chloride, to the compound obtained by this process, to pharmaceutical compositions comprising this compound and their use in the treatment or prevention of viral diseases.N-methyl-4- ...

PICOLINAMIDES WITH FUNGICIDAL ACTIVITY

The invention relates to picolinamides of Formula I and their use as fungicides. 2. A composition according to claim 1 , wherein X is hydrogen and Y is Q.3. A composition according to claim 2 , wherein Ris hydrogen.4. A composition according to claim 3 , wherein Ris OCH.5. A composition according to claim 4 , wherein Ris chosen from hydrogen or methyl.6. A composition according to claim 3 , wherein Ris C(O)R claim 3 , or CHOC(O)R.7. (canceled)8. A composition according to claim 6 , wherein Ris chosen from hydrogen or methyl.9. A composition for the control of a fungal pathogen including at least one of the compositions of and a phytologically acceptable carrier material.10. A composition for the control of a fungal pathogen including at least one of the compositions of and a phytologically acceptable carrier material.11. A composition for the control of a fungal pathogen including mixtures of at least one of the compositions of and another pesticide including fungicides claim 5 , insecticides claim 5 , nematocides claim 5 , miticides claim 5 , arthropodicides claim 5 , bactericides and combinations thereof.12. A composition for the control of a fungal pathogen including mixtures of at least one of the compositions of and another pesticide including fungicides claim 8 , insecticides claim 8 , nematocides claim 8 , miticides claim 8 , arthropodicides claim 8 , bactericides and combinations thereof.13Zymoseptoria triticiPuccinia triticinaPuccinia striiformisVenturia inaequalisUstilago maydisUncinula necatorRhynchosporium secalisPyricularia oryzaePhakopsora pachyrhiziLeptosphaeria nodorumBlumeria graministriticiBlumeria graminishordeiErysiphe cichoracearumColletotrichum lagenariumCercospora beticolaAlternaria solaniPyrenophora teres. The composition according to wherein the fungal pathogen is one of Leaf Blotch of Wheat () claim 1 , Wheat Brown Rust () claim 1 , Stripe Rust () claim 1 , Scab of Apple () claim 1 , Blister Smut of Maize () claim 1 , Powdery Mildew of ...

METHOD FOR PRODUCING BENZOXAZOLE COMPOUND

A method is provided for producing a compound represented by formula (3), wherein n is 1, 2, 3 or 4, by mixing a compound represented by formula (2), a tri(C1-C3 alkyl)silyl(C1-C4 perfluoroalkane) and a fluoride. A method for producing the compound represented by formula (3) contains a step for producing the compound represented by formula (2) by an intramolecular dehydration condensation of a compound represented by formula (1) and by a step for mixing the compound represented by formula (2), a tri(C1-C3 alkyl)silyl(C1-C4 perfluoroalkane) and a fluoride. The present invention relates to a method for preparing 2-(3-ethylsulfonylpyridin-2-yl)-5-(perfluoroalkanesulfonyl)benzoxazole having a control efficacy on harmful organisms and its preparation intermediates.Patent Document 1 discloses 2-(3-ethylsulfonylpyridin-2-yl)-5-(perfluoroalkanesulfonyl)benzoxazole compound, which has a control efficacy on harmful organisms, and a process for preparing 2-(3-ethylsulfonylpyridin-2-yl)-5-(trifluoromethylsulfonyl)benzoxazole, for example, by reacting 2-amino-4-(trifluoromethylsulfanyl)phenol with 3-ethylsulfanyl picolinate followed by ring-closing and oxidizing the resulting compound.Patent Document 1: WO 2014/104407 pamphletThe present invention provides a novel method for preparing 2-(3-ethylsulfonylpyridin-2-yl)-5-(perfluoroalkanesulfonyl)benzoxazole compound.The present inventor has studied to solve the problem and, as a result, found out a method for preparing a compound represented by formula (3):wherein n is 1, 2, 3, or 4,tri(C1-C3 alkyl)silyl(C1-C4 perfluoroalkane), and a fluoride.Namely, the present invention is as follows.wherein n is 1, 2, 3, or 4(hereinafter, referred to as “compound (2)”), tri(C1-C3 alkyl)silyl(C1-C4 perfluoroalkane), and a fluoride.(hereinafter, referred to as “compound (1)”), and a step of mixing the compound (2), tri(C1-C3 alkyl)silyl(C1-C4 perfluoroalkane), and a fluoride.According to the present invention, the compound (3) can be prepared by a ...

PYRIDINE DERIVATIVES

The invention relates to compound of formula (I) 2. A compound according to claim 1 , wherein Ris alkoxycarbonylpyrrolidinylalkoxy claim 1 , alkoxycarbonylpyrrolidinyloxy claim 1 , alkylsulfonylphenylalkoxy claim 1 , (alkyl)(halo)cycloalkylalkoxy claim 1 , benzotriazolyloxy claim 1 , halopyridinylalkoxy or halopyridinyl.3. A compound according to claim 1 , wherein Ris tert.-butyloxycarbonylpyrrolidinylmethoxy claim 1 , butyloxycarbonylpyrrolidinyloxy claim 1 , methyl sulfonylphenylmethoxy claim 1 , (methyl)(difluoro)cyclopropylmethoxy claim 1 , benzotriazolyloxy claim 1 , fluoropyridinylmethoxy or fluoropyridinyl.4. A compound according to claim 1 , wherein Ris haloalkyl claim 1 , cycloalkylalkoxy claim 1 , 2-oxa-6-azaspiro[3.3]heptyl or phenylalkoxy.5. A compound according to claim 1 , wherein Ris hydrogen claim 1 , trifluoromethyl claim 1 , cyclopropylmethoxy claim 1 , 2-oxa-6-azaspiro[3.3]heptyl or phenylmethoxy.6. A compound according to claim 1 , wherein Ris —C(O)—NH—C(O)—NH—C(RR)(CH)—Ror tert.-butyloxadiazolyl.7. A compound according to claim 1 , wherein Ris hydroxyl claim 1 , alkoxycarbonyl claim 1 , aminocarbonyl or alkylaminocarbonyl.8. A compound according to claim 1 , wherein Ris hydroxyl claim 1 , methoxycarbonyl claim 1 , aminocarbonyl or methylaminocarbonyl.913.-. (canceled)14. A pharmaceutical composition comprising a compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a therapeutically inert carrier.1517.-. (canceled)18. A method for the treatment of pain claim 1 , neuropathic pain claim 1 , asthma claim 1 , osteoporosis claim 1 , inflammation claim 1 , psychiatric diseases claim 1 , psychosis claim 1 , oncology claim 1 , encephalitis claim 1 , malaria claim 1 , allergy claim 1 , immunological disorders claim 1 , arthritis claim 1 , gastrointestinal disorders claim 1 , psychiatric disorders rheumatoid arthritis claim 1 , psychosis or allergy claim 1 , which method comprises administering an effective ...

Insecticidal compounds

The present invention relates to novel triazole derivatives of formula (I) having insecticidal activity, to processes and intermediates for preparing them, to insecticidal, acaricidal, nematicidal or molluscicidal compositions comprising them and to methods of using them to combat and control insect, acarine, nematode or mollusc pests wherein Y, X 1 , X 2 and Q are as defined in claim 1 ; or salts thereof.

3-AMIDOBENZAMIDES AND USES THEREOF FOR INCREASING CELLULAR LEVELS OF A3G AND OTHER A3 FAMILY MEMBERS

Disclosed are novel benzamide compounds and the uses thereof for treating diseases and disorders in a patient in need thereof by increasing cellular levels of A3G and/or other members of the A3 family of proteins in the patient. The disclosed compounds include -benzamide compounds that may be administered to treat an HIV-1 infection or cancer in a patient. 2. The compound of claim 1 , wherein n is 0.3. The compound of claim 1 , wherein X is C.4. The compound of claim 1 , wherein Ris methoxy.6. The compound of claim 5 , wherein Ris C1-C6-alkoxy.7. The compound of claim 5 , wherein Ris H claim 5 , C1-C6-alkyl optionally substituted with C1-C6-alkoxy claim 5 , hydroxyl claim 5 , C1-C6-alkylamino claim 5 , C1-C6 dialkylamino claim 5 , phenyl claim 5 , benzyl claim 5 , benzo[1 claim 5 ,3]diox8yl claim 5 , pyridin-2-yl claim 5 , pyridin-3-yl claim 5 , pyridin-4-yl claim 5 , C3-C6-cycloalkyl optionally substituted with methyl claim 5 , C1-C6-alkoxy claim 5 , N-piperidinyl claim 5 , and tetrahydrofuran-2-yl.8. The compound of claim 5 , wherein R claim 5 , R claim 5 , R claim 5 , R claim 5 , and Rare independently selected from H claim 5 , C1-C6-alkoxy claim 5 , and halo.9. The compound of claim 5 , wherein one or more of R claim 5 , R claim 5 , are Rare methoxy.10. The compound of claim 9 , wherein one or more of Rand Rare chloro.12. A pharmaceutical composition comprising the compound of and a pharmaceutical carrier.13. The pharmaceutical composition of comprising an effective amount of the compound for increasing levels of A3G and/or other members of the A3 family of proteins after the composition is administereing to a patient in need thereof.14. A method for treating HIV-1 infection in a patient in need thereof claim 13 , the method comprising administering the pharmaceutical composition of to the patient.15. A method for treating cancer in a patient in need thereof claim 13 , the method comprising administering the pharmaceutical composition of to the patient. The ...

KETONE INHIBITORS OF LYSINE GINGIPAIN

The present invention provides compounds according to Formula I as described herein, and their use for inhibiting the lysine gingipain protease (Kgp) from the bacterium . Also described are gingipain activity probe compounds and methods for assaying gingipain activity are also described, as well as methods for the treatment of disorders associated with infection, including brain disorders such as Alzheimer's disease. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of Ccycloalkyl claim 1 , Calkyl claim 1 , Caryl claim 1 , and 5- to 12-membered heteroaryl each of which is optionally substituted with one or more Rsubstituents claim 1 , and each Ris independently selected from the group consisting of halogen claim 1 , —N claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , Chaloalkoxy claim 1 , —N(R) claim 1 , —N(R) claim 1 , and —NRC(O)R.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris Calkyl substituted with Calkoxy.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydrogen.67-. (canceled)8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CHR claim 1 , Ris —O—R claim 1 , and Ris Chaloalkyl.9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CHR claim 1 , Ris —O—R claim 1 , and Ris 5- to 12-membered heteroaryl claim 1 , which is optionally substituted with one or more members independently selected from the group consisting of halogen and Calkyl.10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of —N(R) claim 1 , 5- to 12-membered heteroaryl claim 1 , and 3- to 12-membered heterocyclyl claim 1 , wherein:{'sub': 1-3', '1-3, '5- to 12-membered heteroaryl is optionally substituted with one or more members ...

Aromatic compounds with sulfur containing ligands

Compounds useful as nutritional supplements, antioxidants, heavy metal chelators and/or as intermediates for producing other related compounds with like uses have a formula: where R 1 is an aromatic backbone and R 2 is a sulfur containing ligand.

DEUTERATED OMEGA DIPHENYLUREA RELATED COMPOUNDS AND INTERMEDIATES

Methods and processes for preparation and production of deuterated ω-diphenylurea are disclosed. Especially, a kind of deuterated ω-diphenylurea compounds which can inhibit phosphokinase and the preparation method of N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-d3-methylcarbamoyl)-4-pridinyloxy)phenyl)urea are disclosed. The said deuterated diphenylurea compounds can be used for treating or preventing tumors and relative diseases. 2. The intermediate of formula (B) according to claim 1 , wherein Y is chlorine.4. A p-toluene sulfonate of a deuterated ω-diphenylurea compound being 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl]ureido)-phenoxy)-N-(methyl-d)picolinamide p-toluenesulfonate (CM4307.TsOH). This application is a divisional of U.S. application Ser. No. 13/635,822, filed Sep. 19, 2012, which is a Section 371 of Internation Application No. PCT/CN2011/071926, filed Mar. 17, 2011, which was published in the Chinese language on Sep. 22, 2011, under Internation Publication No. WO 2011/113367 A1 the disclosure of which is incorporated herein by reference.This invention relates to the field of chemical synthesis, and particularly relates to the methods and processes for preparation and production of deuterated ω-diphenylurea.Ω-diphenylurea derivatives are known compounds with c-RAF kinase inhibition activity. For example, WO2000/042012 had disclosed a class of ω-carboxyl-aryl-substituted diphenylurea and the use thereof for treating cancer and related diseases.Initially, ω-diphenylurea compounds, such as Sorafenib, were firstly found as the inhibitor of c-RAF kinase. The other studies had shown that they could also inhibit the MEK and ERK signal transduction pathways and activities of tyrosine kinases including vascular endothelial growth factor receptor-2 (VEGFR-2), vascular endothelial growth factor receptor-3 (VEGFR-3), and platelet-derived growth factor receptor-β (PDGFR-β) (Curr Pharm Des 2002, 8, 2255-2257). Therefore, they were called multi-kinase ...

Pyridyl Reverse Sulfonamides For HBV Treatment

The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention. 12-. (canceled)510-. (canceled)11. A composition comprising a compound according to claim 3 , or a salt claim 3 , solvate claim 3 , or N-oxide thereof claim 3 , further comprising at least one pharmaceutically acceptable carrier.12. A method of treating an HBV infection in an individual in need thereof claim 3 , comprising administering to the individual a therapeutically effective amount of a compound according to .13. The method of claim 12 , further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of an HBV vaccine claim 12 , HBV polymerase inhibitor claim 12 , interferon claim 12 , pegylated interferon claim 12 , viral entry inhibitor claim 12 , viral maturation inhibitor claim 12 , BAY 41-4109 claim 12 , reverse transcriptase inhibitor claim 12 , a TLR-agonist claim 12 , AT-61 ((E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide) claim 12 , and AT-130 ((E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide) claim 12 , and a combination thereof.14. The method of claim 13 , wherein the pegylated interferon is pegylated interferon alpha (IFN-α) claim 13 , pegylated interferon lambda (IFN-λ) claim 13 , or pegylated interferon gamma (IFN-γ).15. The method of claim 13 , wherein the reverse transcriptase inhibitor is at least one of Zidovudine claim 13 , Didanosine claim 13 , Zalcitabine claim 13 , ddA claim 13 , Stavudine claim 13 , Lamivudine claim 13 , Abacavir claim 13 , Emtricitabine claim 13 , Entecavir claim 13 , Apricitabine claim 13 , Atevirapine claim 13 , ribavirin claim 13 , acyclovir claim 13 , famciclovir claim 13 , valacyclovir claim 13 , ganciclovir claim 13 , valganciclovir ...

SUBSTITUTED PYRIDINE COMPOUNDS AS PESTICIDES

The present invention relates to novel substituted pyridine compounds of the formula (I) 2. Compound of formula (I) and/or salt thereof according to in which{'sup': '1', 'Qis in each case optionally singly or multiply, identically or differently substituted phenyl, 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, hetaryl or oxohetaryl,'}{'sub': 5', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '2', '4', '2', '4', '2', '4', '2', '4', '2', '4', '2', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '3', '6', '3', '6', '1', '4', '3', '6', '1', '4', '3', '6', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '3', '6', '3', '6', '3', '6', '3', '6', '3', '6', '3', '6', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '6', '1', '6', '1', '4', '1', '4, 'where the substituents are selected from cyano, halogen, nitro, amino, SF, (C-C)alkyl, (C-C)haloalkyl, (C-C)cyanoalkyl, (C-C)hydroxyalkyl, (C-C)alkoxy-(C-C)alkyl, (C-C)alkenyl, (C-C)haloalkenyl, (C-C)cyanoalkenyl, (C-C)alkynyl, (C-C)haloalkynyl, (C-C)cyanoalkynyl, (C-C)alkoxy, (C-C)haloalkoxy, (C-C)cyanoalkoxy, (C-C)alkoxy-(C-C)alkoxy, (C-C)cycloalkyl, (C-C)halocycloalkyl, (C-C)alkyl-(C-C)cycloalkyl, (C-C)haloalkyl-(C-C)cycloalkyl, (C-C)haloalkenoxy, (C-C)alkylhydroxyimino, (C-C)alkoxyimino, (C-C)alkyl-(C-C)alkoxyimino, (C-C)haloalkyl-(C-C)alkoxyimino, (C-C)alkylsulphanyl, (C-C)alkylsulphanyl-(C-C)alkyl, (C-C)alkylsulphinyl, (C-C)haloalkylsulphinyl, (C-C)alkylsulphinyl-(C-C)alkyl, (C-C)alkylsulphonyl, (C-C)haloalkylsulphonyl, (C-C)alkylsulphonyl-(C-C)alkyl, (C-C)alkylsulphonyloxy, (C-C)haloalkylsulphanyl, (C-C)cycloalkylsulphanyl, (C-C)halocycloalkylsulphanyl, (C-C)cycloalkylsulphonyl, (C-C)halocycloalkylsulphonyl, (C-C)cycloalkylsulphinyl, (C-C)halocycloalkylsulphinyl, (C-C)alkylcarbonyl, (C-C)haloalkylcarbonyl, aminocarbonyl, (C-C ...

Chemical Compound Manufacture, New Salt Form, And Therapeutic Uses Thereof

There is disclosed a method of preparing a compound of Formula (1), or a salt thereof (1) the method comprising: a) treating a compound of Formula (2) sequentially with o-tolylmagnesium chloride, N-methylpiperazine and iodine, under conditions sufficient to obtain a compound of Formula (3) b) treating the compound of Formula (3) from step a) with 3,5-bis(trifluoromethyl)benzyl bromide and a suitable base, under conditions sufficient to obtain a compound of Formula (1). 3. A method according to claim 1 , wherein step (a) is conducted in THF claim 1 , and preferably Formula (2) is added to 1M o-tolylmagnesium chloride in THF at about 0° C.4. A method according to claim 1 , wherein Formula (2) is added to 1M o-tolylmagnesium chloride in THF at about 0° C. claim 1 , preferably over about 1 hr claim 1 , and the reaction is warmed to about 20° C.5. A method according to claim 1 , wherein N-methylpiperazine is added at about 20° C.6. A method according to claim 1 , wherein about 5 M equivalents of N-methylpiperazine is added claim 1 , preferably in one portion.7. A method according to claim 6 , wherein the reaction mixture is cooled claim 6 , preferably to about 5° C. claim 6 , after the reaction mixture is stirred for at least 10 hours at about 20° C.8. A method according to claim 7 , wherein to the cooled reaction mixture is added AcOH claim 7 , preferably about 7% AcOH in water.9. A method according to claim 1 , wherein iodine is subsequently reacted as a THF solution claim 1 , preferably about 1.5 mol equivalents claim 1 , preferably under nitrogen at about 0° C.10. A method according to claim 1 , wherein the base of step b) is potassium tert-butoxide claim 1 , preferably in an amount of about 1.5 mol equivalents relative to Formula (3).11. A method according to claim 1 , wherein 3 claim 1 ,5-Bis(trifluoromethyl)benzyl bromide is reacted with Formula (3) at about 1.2 mol equivalent.12. A method according to claim 1 , wherein the compound of Formula (3) is purified by a ...

Method for Preparing Indolenaphthopyrans

Provided is a synthetic intermediate for the preparation of photochromic indolenaphthopyran compounds having the core skeletal structure of Formula (I): wherein m is 0 to 4, n is 0 to 4, Rand Rare each independently hydroxyl, cyano, (meth)acrylate, amino, halo, substituted or unsubstituted alkyl, boronic ester, boronic acid, polyether, polyester, polycarbonate, polyurethane, substituted or unsubstituted aryl, substituted or unsubstituted heterocycloaryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted arylthio, ketone, aldehyde, ester, carboxylic acid, carboxylate, amide, carbonate, carbamate, urea, siloxane, alkoxysilane, or polysiloxane; Ris substituted or unsubstituted 2-pyridyl or substituted or unsubstituted 2-quinolyl; and Ris hydrogen, substituted or unsubstituted alkyl, alkoxymethyl, substituted or unsubstituted silyl, or acyl. Also provided is a process for producing an indolenaphthol compound which includes cyclizing the phenylnaphthol compound of Formula (I) in the presence of a catalyst. 2. The phenylnaphthol compound of claim 1 , wherein each alkyl substituent claim 1 , each aryl substituent claim 1 , each heterocycloalkyl substituent claim 1 , each heteroaryl substituent claim 1 , each alkoxy substituent claim 1 , each aryloxy substituent claim 1 , each alkylthio substituent claim 1 , each arylthio substituent claim 1 , and each each silyl substituent is in each case independently selected from halogen claim 1 , cyano claim 1 , nitro claim 1 , alkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , haloalkyl claim 1 , perhaloalkyl claim 1 , heterocycloalkyl claim 1 , aryl claim 1 , heteroaryl claim 1 , alkoxy claim 1 , hydroxyl claim 1 , alkylthio claim 1 , arylthio claim 1 , ketone claim 1 , aldehyde claim 1 , ester claim 1 , carboxylic acid claim 1 , carboxylate claim 1 , siloxane claim 1 , alkoxysilane claim 1 , ...

Synthesis of carbamoylpyridone hiv integrase inhibitors and intermediates

A synthesis approach providing an early ring attachment via a bromination to compound l-l yielding compound II-Il, whereby a final product such as AA can be synthesized. In particular, the 2,4-difluorophenyl-containing sidechain is attached before creation of the additional ring Q.

SUBSTITUTED 3-HETEROAROYLAMINO-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PHARMACEUTICALS

The present invention relates to compounds of the formula I, 9. A compound of the formula I claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , selected from:(S)-3-[(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-amino]-3-o-tolyl-propionic acid3-Biphenyl-4-yl-3-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-propionic acid(S)-3-[(6-Methylamino-pyrazine-2-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(5-Methyl-pyrazine-2-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(6-Chloro-pyrazine-2-carbonyl)-amino]-3-o-tolyl-propionic acid3-(2-Chloro-phenyl)-3-[(pyrazine-2-carbonyl)-amino]-propionic acid3-(2-Chloro-phenyl)-3-[(5-methyl-pyrazine-2-carbonyl)-amino]-propionic acid3-(2-Chloro-phenyl)-3-[(6-methylamino-pyrazine-2-carbonyl)-amino]-propionic acid(S)-3-[(2,6-Dimethoxy-pyrimidine-4-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(2,6-Bis-dimethylamino-pyrimidine-4-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(4,6-Dimethoxy-pyrimidine-2-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(2-Amino-6-isobutyl-pyrimidine-4-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(2,6-Dimethyl-pyrimidine-4-carbonyl)-amino]-3-o-tolyl-propionic acid3-[(2-Amino-6-isopropyl-pyrimidine-4-carbonyl)-amino]-3-(2-chloro-phenyl)-propionic acid3-(2-Chloro-phenyl)-3-[(4,6-dimethoxy-pyrimidine-2-carbonyl)-amino]-propionic acid3-(2-Chloro-phenyl)-3-[(2,6-dimethoxy-pyrimidine-4-carbonyl)-amino]-propionic acid3-[(2-Amino-6-isobutyl-pyrimidine-4-carbonyl)-amino]-3-(2-chloro-phenyl)-propionic acid3-[(2,6-Bis-dimethylamino-pyrimidine-4-carbonyl)-amino]-3-(2-chloro-phenyl)-propionic acid and3-(2-Chloro-phenyl)-3-[(6-phenyl-2-piperidin-1-yl-pyrimidine-4-carbonyl)-amino]-propionic acid.11. A pharmaceutical composition comprising the compound of or a physiologically acceptable salt thereof or a physiologically acceptable solvate of any of them.12. The pharmaceutical composition of claim 11 , further ...

PICOLINAMIDES AS FUNGICIDES

This disclosure relates to picolinamides of Formula I and their use as fungicides. 2. A compound according to claim 1 , wherein X and Y are hydrogen.3. A compound according to claim 2 , wherein Rand Rare independently hydrogen or alkyl.4. A compound according to claim 2 , wherein Rand Rare independently hydrogen or methyl.5. A compound according to claim 2 , wherein Ris aryl claim 2 , optionally substituted with 0 claim 2 , 1 or multiple R.6. A compound according to claim 2 , wherein Ris alkyl claim 2 , aryl claim 2 , or heteroaryl claim 2 , each optionally substituted with 0 claim 2 , 1 or multiple R.7. A compound according to claim 2 , wherein Rand Rare independently hydrogen or alkyl claim 2 , Rand Rare independently chosen from hydrogen or methyl claim 2 , Ris aryl claim 2 , optionally substituted with 0 claim 2 , 1 or multiple R claim 2 , and Ris chosen from alkyl claim 2 , aryl claim 2 , or heteroaryl claim 2 , each optionally substituted with 0 claim 2 , 1 or multiple R.8. A compound according to claim 1 , wherein X is C(O)Rand Y is hydrogen.9. A compound according to claim 8 , wherein Rand Rare independently hydrogen or alkyl.10. A compound according to claim 8 , wherein Rand Rare independently hydrogen or methyl.11. A compound according to claim 8 , wherein Ris aryl claim 8 , optionally substituted with 0 claim 8 , 1 or multiple R;12. A compound according to claim 8 , wherein Ris alkyl claim 8 , aryl claim 8 , or heteroaryl claim 8 , each optionally substituted with 0 claim 8 , 1 or multiple R.13. A compound according to claim 8 , wherein Rand Rare independently hydrogen or alkyl claim 8 , Rand Rare independently chosen from hydrogen or methyl claim 8 , Ris aryl claim 8 , optionally substituted with 0 claim 8 , 1 or multiple R claim 8 , and Ris chosen from alkyl claim 8 , aryl claim 8 , or heteroaryl claim 8 , each optionally substituted with 0 claim 8 , 1 or multiple R.14. A compound according to claim 1 , wherein X is hydrogen and Y is Q.15. A compound ...

PICOLINAMIDES AS FUNGICIDES

This disclosure relates to picolinamides of Formula I and their use as fungicides. 2. A composition according to claim 1 , wherein X is hydrogen and Y is Q.3. A composition according to claim 2 , wherein Ris alkoxy.4. A composition according to claim 3 , wherein W is O claim 3 , or S.5. A composition according to claim 4 , wherein Ris hydrogen.6. A composition according to claim 5 , wherein Rand Rare independently hydrogen or alkyl.7. A composition according to claim 5 , wherein Rand Rare independently hydrogen or methyl.8. A composition according to claim 5 , wherein Ris aryl claim 5 , optionally substituted with 0 claim 5 , 1 or multiple R;9. A composition according to claim 5 , wherein Ris alkyl claim 5 , aryl claim 5 , or heteroaryl claim 5 , each optionally substituted with 0 claim 5 , 1 or multiple R.10. A composition according to claim 5 , wherein Rand Rare independently hydrogen or alkyl claim 5 , Rand Rare independently hydrogen or methyl claim 5 , Ris aryl claim 5 , optionally substituted with 0 claim 5 , 1 or multiple R; and Ris alkyl claim 5 , aryl claim 5 , or heteroaryl claim 5 , each optionally substituted with 0 claim 5 , 1 or multiple R.11. A composition according to claim 4 , wherein Ris —C(O)R claim 4 , or —CHOC(O)R.12. A composition according to claim 11 , wherein Ris alkyl claim 11 , optionally substituted with 0 claim 11 , 1 or multiple R.13. A composition according to claim 12 , wherein Rand Rare independently hydrogen or alkyl.14. A composition according to claim 12 , wherein Rand Rare independently hydrogen or methyl.15. A composition according to claim 12 , wherein Ris aryl claim 12 , optionally substituted with 0 claim 12 , 1 or multiple R;16. A composition according to claim 12 , wherein Ris alkyl claim 12 , aryl claim 12 , or heteroaryl claim 12 , each optionally substituted with 0 claim 12 , 1 or multiple R.17. A composition according to claim 12 , wherein Rand Rare independently hydrogen or alkyl claim 12 , Rand Rare independently ...

Picolinamide n-oxide compounds with fungicidal activity

This disclosure relates to picolinamide N-oxides of Formula I and their use as fungicides.

PROCESS FOR THE PREPARATION OF 4-CARBONYL)AMINO]-3-FLUOROPHENOXY}-N-ETHYLPYRIDINE-2-CARBOXAMIDE, ITS SALTS AND MONOHYDRATE

The present invention relates to a process for preparing 4-{4-[({[4-chloro-3-(trifluoromethyl)-phenyl]amino}carbonyl)amino]-3-fluorophenoxy}-N-methylpyridine-2-carboxamide, its salts and monohydrate. 2. The process of for preparing the monohydrate of the compound of the formula (I) wherein the salt of the compound of the formula (I) is then treated with an aqueous basic solution to precipitate the monohydrate of the compound of the formula (I).3. The process of wherein the monohydrate of the compound of the formula (I) precipitates at a temperature of from 35° C. to 45° C.4. The process of for preparing of the compound of the formula (I) wherein the monohydrate is dried under reduced pressure until the compound of the formula (I) is formed.5. The process of wherein the solution comprising the solved compound of the formula (I) and what from the salt of the compound of the formula (I) precipitates is the reaction mixture or is a separate solution of the compound of the formula (I) prepared after isolation of the compound of the formula (I) from the reaction mixture.6. The process of wherein the acid is generated in situ in the reaction mixture after the compound of the formula (I) is formed by adding to the reaction mixture a protic substance and an acid precursor.7. The process of wherein the acid is generated in situ in the reaction mixture after the compound of the formula (I) is formed by adding to the reaction mixture an alcohol and an acylchloride.8. The process of wherein the alcohol is ethanol and the acylchloride is acetylchloride.11. The process of wherein the compound of the formula (II) is used in a solution of a suitable organic solvent which solution is prepared by neutralization the hydrochloric acid salt of the compound of the formula (II) with a base.12. The process of wherein the compound of the formula (II) it is solved in a suitable organic solvent claim 9 , treated with an acid which is generated in situ by adding a protic substance and an acid ...

MITOCHONDRIAL ALDEHYDE DEHYDROGENASE-2 BINDING COMPOUNDS AND METHODS OF USE THEREOF

The present invention provides compounds that bind to mitochondrial aldehyde dehydrogenase-2 (ALDH2), methods of using said compounds to treat patients with Fanconi Anemia, and methods of preparing said compounds. 2109-. (canceled)117. The compound according to claim 1 , wherein the compound is selected from Table 1.122. A method for treating and/or preventing peripheral artery disease in a subject in need thereof claim 1 , comprising administering to the subject the compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , ester claim 1 , or prodrug thereof.123. A method for treating and/or preventing liver injury and/or damage in a subject in need thereof claim 1 , comprising administering to the subject the compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , ester claim 1 , or prodrug thereof.124. The method of claim 123 , wherein the liver injury and/or damage is liver fibrosis.125. A method for treating and/or preventing Acute Inflammatory Pain in a subject in need thereof claim 1 , comprising administering to the subject the compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , ester claim 1 , or prodrug thereof.126. A method for treating and/or preventing alcohol intolerance claim 1 , alcohol addiction claim 1 , an alcohol abuse disorder claim 1 , alcohol intoxication claim 1 , alcohol dependence claim 1 , alcohol poisoning claim 1 , or symptoms of alcohol consumption claim 1 , comprising administering to the subject the compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , ester claim 1 , or prodrug thereof.127. The method of claim 126 , wherein the alcohol poisoning is acute alcohol poisoning.128. The method of claim 126 , wherein the alcohol intoxication is acute alcohol intoxication. This application claims priority to, and the benefit of, U.S. provisional application No. 61/941,909, filed Feb. 19, 2014, the entire content ...

AMIDE COMPOUNDS AND PREPARATION METHOD THEREFOR AND USE THEREOF

Provided are amide compounds and a preparation method therefor and the use thereof. The amide compounds have a structure represented by formula I. The amide compounds of the present invention have high insecticidal activity at a low dosage and have a good fast-acting property. The dosage of the pesticide will be reduced during application due to the good insecticidal activity of the amide compounds at low dosage, which is more conducive to environmental protection and has broad application prospect. 2. The amide compound according to claim 1 , wherein claim 1 , Z claim 1 , Z claim 1 , Z claim 1 , Z claim 1 , and Zare independently of each other H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , CN claim 1 , NO claim 1 , methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , i-propyl claim 1 , c-propyl claim 1 , n-butyl claim 1 , t-butyl claim 1 , i-butyl claim 1 , n-pentyl claim 1 , 1-methylbutyl claim 1 , 2-methylbutyl claim 1 , 3-methylbutyl claim 1 , 1 claim 1 ,1-dimethylpropyl claim 1 , 1 claim 1 ,2-dimethylpropyl claim 1 , 2 claim 1 ,2-dimethylpropyl claim 1 , methoxyl claim 1 , ethoxyl claim 1 , n-propoxyl claim 1 , i-propoxyl claim 1 , t-butoxyl claim 1 , trifluoromethyl claim 1 , pentafluoroethyl claim 1 , heptafluoropropyl claim 1 , heptafluoroisopropyl claim 1 , difluoromethoxyl claim 1 , trifluoromethoxyl claim 1 , pentafluoroethoxyl claim 1 , methylsulfinyl claim 1 , trifluoromethylsulfinyl claim 1 , methylsulfonyl or trifluoromethylsulfonyl;{'sub': '2', 'Ris H, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, n-pentyl, 2-pentyl, neopentyl, isopentyl, 4-methyl-2-pentyl, n-hexyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monochloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoroisopropyl, cyclopropyl, cyclobutyl, cyclopentyl, perfluorocyclopropyl, perfluorocyclobutyl or perfluorocyclopentyl; and'}{'sub': '3', 'Ris H, F or Cl.'}3. The amide compound according to claim 1 , wherein claim 1 , Z claim 1 , Z ...

DEUTERIUM-ENRICHED HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE ENZYME INHIBITORS

Provided herein are deuterium-enriched compounds of Formula (I), Formula (II), Formula (III), Formula (IV), Formula (V), and Formula (VI). Pharmaceutical compositions comprising the isotope-enriched compounds, and methods of using such compounds are also provided. 2. The compound of claim 1 , wherein one of Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , and Yis isotopically enriched with deuterium claim 1 , and the others are non-enriched hydrogens.3. The compound of claim 1 , wherein two of Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , and Yare isotopically enriched with deuterium claim 1 , and the others are non-enriched hydrogens.4. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare hydrogen.6. The compound of claim 5 , wherein one of Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , YYand Yis isotopically enriched with deuterium claim 5 , and the others are non-enriched hydrogens.7. The compound of claim 5 , wherein two of Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , and Yare isotopically enriched with deuterium claim 5 , and the others are non-enriched hydrogens.8. The compound of claim 5 , wherein Y claim 5 , Y claim 5 , and Yare hydrogen.10. The compound of claim 9 , wherein one of Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Yand Yis isotopically enriched with deuterium claim 9 , and the others are non-enriched hydrogens.11. The compound of claim 9 , wherein two of Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , Y claim 9 , and Yare ...

Process for Preparing 2-[[5-(3-Chlorophenyl)-3-Hydroxypyridine-2-Carbonyl]Amino]Acetic Acid

Disclosed herein are methods and processes of preparing vadadustat and pharmaceutically acceptable salts thereof, and intermediates of formula (I) and their salts useful for the synthesis of vadadustat. 2. The process of claim 1 , wherein Ris t-butyl.3. The process of or claim 1 , wherein Ris methyl.4. The process of any one of - claim 1 , wherein the hydrolyzing agent comprises an acid.5. The process of any one of - claim 1 , wherein the hydrolyzing agent comprises a base.6. The process of claim 5 , wherein the base is an alkali metal hydroxide claim 5 , alkali metal carbonate claim 5 , Polymer-SK or tetrabutylammonium fluoride (TBAF).7. The process of claim 5 , wherein the base is an alkali metal hydroxide selected from lithium hydroxide (LiOH) claim 5 , sodium hydroxide (NaOH) claim 5 , potassium hydroxide (KOH) claim 5 , cesium hydroxide (CsOH) claim 5 , and any combination thereof.8. The process of claim 5 , wherein the base is an alkali metal carbonate selected from lithium carbonate (LiCO) claim 5 , sodium carbonate (NaCO) claim 5 , potassium carbonate (KCO) claim 5 , cesium carbonate (CsCO) claim 5 , and any combination thereof.9. The process of claim 7 , wherein the alkali metal hydroxide is potassium hydroxide (KOH).10. The process of any one of - claim 7 , which occurs in presence of a solvent comprising N claim 7 ,N-dimethylformide (DMF) claim 7 , t-butanol claim 7 , dimethoxyethane (DME) claim 7 , acetonitrile claim 7 , dichloromethane (DCM) claim 7 , tetrahydrofuran (THF) claim 7 , 2-methyltetrahydrofuran (ME-THF) claim 7 , isopropyl alcohol claim 7 , methanol claim 7 , ethanol claim 7 , or any combination thereof.11. The process of claim 10 , wherein the solvent comprises 2-methyltetrahydrofuran (ME-THF).12. The process of any one of - claim 10 , wherein the purity of the compound of Formula (8) is at least 99%.14. The process of claim 13 , wherein step c) is required.15. The process of or claim 13 , wherein the compound of Formula (I) comprises less ...

NEMATICIDAL N-(PHENYLCYCLOALKYL)CARBOXAMIDES AND N-(PHENYLCYCLOALKYL)THIOCARBOXAMIDES

The present invention relates to the use of N-(Phenylcycloalkyl)carboxamides and N-(Phenylcycloalkyl)thiocarboxamides for the control of nematodes in agriculture and as anthelmintic agents against endoparasites in animals and humans, compositions containing such compounds and methods for the control of nematodes and helminths and furthermore to novel N-(Phenylcycloalkyl)carboxamides and N-(Phenylcycloalkyl)thiocarboxamides, processes and intermediate compounds for their preparation, their use as nematicides, compositions containing such compounds and methods for the control of nematodes. 3. A compound according to claim 1 , in which T represents sulphur claim 1 , capable of being used for controlling nematodes.6. Composition claim 1 , comprising an effective amount of at least one compound of formula (I-1) or (I-2) and at least one surfactant claim 1 , solid or liquid diluent.7. A compound according to capable of being used as an endoparasiticide.8. A compounds according to capable of being used as an anthelmintic.9. A compound according to capable of being used for preparation of an endoparasitic agent for combating one or more endoparasites. The present invention relates to the use of N-(Phenylcycloalkyl)carboxamides and N-(Phenylcycloalkyl)thiocarboxamides for the control of nematodes in agriculture and as anthelmintic agents against endoparasites in animals and humans, compositions containing such compounds and methods for the control of nematodes and helminths.The present invention further relates to novel N-(Phenylcycloalkyl)carboxamides and N-(Phenylcycloalkyl)thiocarboxamides, processes and intermediate compounds for their preparation, their use as nematicides, compositions containing such compounds and methods for the control of nematodes.Nematodes cause a substantial loss in agricultural product including food and industrial crops and are controlled with chemical compounds having nematicidal activity. To be useful in agriculture these compounds should have ...

ANTIMICROBIAL PYRIDINOHYDRAZIDE AND HYDRAZOMETHYLPYRIDINE-BASED AGENTS

A class of modified salicylaldehyde derivatives has also been synthesized and a series of modified pyridine-based hydrazones identified that have potent antimicrobial activity against multiple spp. These compounds have been characterized using fungal growth inhibition assays, mammalian cell toxicity assays, time-kill assays and synergy studies of these novel pyridine-based hydrazones on both azole-susceptible and azole-resistant fungal species. Effectiveness of these compounds in inhibiting the growth of protozoal parasites was also found. 2. The compound of claim 1 , wherein Ris an ester having the forty OCOX claim 1 , wherein X is selected from the group consisting of: methyl claim 1 , ethyl claim 1 , cyclopentane cycloheptane claim 1 , CHCH claim 1 , phenyl claim 1 , 3 claim 1 ,4 claim 1 ,5-trimethoxyphenyl 2-acetyloxphenyl claim 1 , 2-pyridinyl claim 1 , 3-pyridiyl claim 1 , and 4-pyridinyl.3. The compound of claim 1 , wherein Ris selected from the group consisting of: phenyl claim 1 , 4-methylphenyl claim 1 , 4-methoxyphenyl 4-t-butyiphenyl claim 1 , 4-hydroxyphenyl claim 1 , 4-nitrophenyl claim 1 , 4-chlorophenyl claim 1 , 4-bromophenyl claim 1 , 4-iodophenyl claim 1 , 3 claim 1 ,4-dichlorophenyl claim 1 , 3 claim 1 ,4-dimethylphenyl claim 1 , 2-pyridinyl claim 1 , 3-pyridinyl claim 1 , 2-hydroxy-3 pyridinyl claim 1 , 4-pyridinyl claim 1 , 1-oxidopyridin-2-yl claim 1 , 1-oxidopyridin-3-yl claim 1 , and 1-oxidopyridin-4-yl.5. The compound of . wherein Ris an ester eying the formula OCOX claim 4 , wherein X is selected from the group consisting of: methyl claim 4 , ethyl claim 4 , oyclopentane claim 4 , cycloheptane claim 4 , CHCH claim 4 , phenyl claim 4 , 3 claim 4 ,4 claim 4 ,5-trimethoxyphenyl claim 4 , 2-acetyloxyphenyl claim 4 , 2-pyridinyl claim 4 , 3-pyridinyl claim 4 , and 4-pyridinyl.6. The compound of claim 4 , wherein Ris selected from the group consisting of: phenyl claim 4 , 4-methylphenyl claim 4 , 4-methoxyphenyl claim 4 , 4-t-butylphenyl claim 4 ...

PHARMACEUTICAL COMPOSITION CONTAINING CRYSTALLINE SORAFENIB TOSYLATE

The present invention relates to an oral solid dosage form, in particular a tablet, comprising sorafenib tosylate polymorphic form III. 1. An oral solid dosage form , comprising a crystalline sorafenib tosylate characterized by an X-ray powder diffraction pattern showing peak maxima at 2 theta/° values of 7.7±0.2 , 12.0±0.2 , 19.9±0.2 , and 21.6±0.2 , the X-ray powder diffraction pattern being determined at a temperature of about 22° C. using copper-Kalpha1/2 radiation having a wavelength of 0.15419 nm , and at least one excipient.215-. (canceled)16. The dosage form of claim 1 , comprising a crystalline sorafenib tosylate characterized by a Raman spectrum showing peak maxima at Raman shift/cmvalues of 1715±5 claim 1 , 1601±5 claim 1 , 1334±5 claim 1 , 1268±5 claim 1 , 1033±5 claim 1 , and 1011±5 claim 1 , the Raman spectrum being determined using a laser having a wavelength of 532 nm wherein the exposure time of the sample is 2 s claim 1 , and at least one excipient.17. The dosage form according to claim 1 , comprising at least 90% by weight claim 1 , relative to the total amount of sorafenib tosylate claim 1 , of the crystalline sorafenib tosylate according to18. The dosage form of claim 1 , comprising at most 5% by weight claim 1 , relative to the crystalline sorafenib tosylate according to claim 1 , of a crystalline sorafenib tosylate characterized by an X-ray powder diffraction pattern showing peak maxima at 2 theta/° values of 4.3±0.2 claim 1 , 11.0±0.2 claim 1 , 14.8±0.2 claim 1 , 17.9±0.2 claim 1 , 19.3±0.2 claim 1 , 20.5±0.2 and 20.8±0.2 claim 1 , 21.5±0.2 claim 1 , 22.9±0.2 claim 1 , 24.5±0.2 claim 1 , the X-ray powder diffraction pattern being determined at a temperature of about 22° C. using copper-Kalpha1/2 radiation having a wavelength of 0.15419 nm claim 1 , and/or of a crystalline sorafenib tosylate characterized by a Raman spectrum showing peak maxima at Raman shift/cmvalues of 1688±5 claim 1 , 1612±5 claim 1 , 1601±5 claim 1 , 1325±5 claim 1 , 1310± ...

INSECTICIDAL COMPOUNDS

The present invention relates to novel triazole derivatives of formula (I) having insecticidal activity, to processes and intermediates for preparing them, to insecticidal, acaricidal, nematicidal or molluscicidal compositions comprising them and to methods of using them to combat and control insect, acarine, nematode or mollusc pests 3. A compound of formula (I) according to characterized in thatR is hydrogen or ethyl.4. A compound of formula (I) according to characterized in that Y is chlorine claim 1 , bromine or iodine.5. A compound of formula (I) according to characterized in that Q is a group selected from Q2 claim 1 , Q3 claim 1 , Q4 and Q5.6. A method of controlling insects claim 1 , acarines claim 1 , nematodes or molluscs which comprises applying to a pest claim 1 , to a locus of a pest claim 1 , or to a plant susceptible to attack by a pest an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in .7. An insecticidal claim 1 , acaricidal claim 1 , nematicidal or molluscicidal composition comprising an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in together with an agrochemically acceptable diluent or carrier.8. A composition according to which further comprises one or more additional insecticidal claim 7 , acaricidal claim 7 , nematicidal or molluscicidal compounds.9. A method of protecting useful plants from insects claim 1 , acarines claim 1 , nematodes or molluscs claim 1 , comprising applying to said plants claim 1 , to the locus thereof claim 1 , or to plant propagation material thereof claim 1 , an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in . This application is a continuation of U.S. patent application Ser. No. 15/824,099, filed 28 Nov. 2017, which is a divisional of U.S. ...

INSECTICIDAL COMPOUNDS

The present invention relates to novel triazole derivatives of formula (I) having insecticidal activity, to processes and intermediates for preparing them, to insecticidal, acaricidal, nematicidal or molluscicidal compositions comprising them and to methods of using them to combat and control insect, acarine, nematode or mollusc pests 3. A compound of formula (I) according to wherein{'sub': '1', 'Xis hydrogen, fluorine or methoxy'}{'sub': 2', '2', '1, 'Xis hydrogen or cyano, with the condition that if Xis cyano, then Xis hydrogen,'}R is hydrogen, methyl or ethyl.4. A compound of formula (I) according to wherein{'sub': 1', '2, 'Xis methoxy and Xis hydrogen.'}5. A compound of formula (I) according to wherein{'sub': 2', '1, 'Xis cyano and Xis hydrogen.'}7. A method of controlling insects claim 4 , acarines claim 4 , nematodes or molluscs which comprises applying to a pest claim 4 , to a locus of a pest claim 4 , or to a plant susceptible to attack by a pest an insecticidally claim 4 , acaricidally claim 4 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in 1.8. An insecticidal claim 4 , acaricidal claim 4 , nematicidal or molluscicidal composition comprising an insecticidally claim 4 , acaricidally claim 4 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in 1 together with an agrochemically acceptable diluent or carrier.9. A composition according to which further comprises one or more additional insecticidal claim 8 , acaricidal claim 8 , nematicidal or molluscicidal compounds.10. A method of protecting useful plants from insects claim 1 , acarines claim 1 , nematodes or molluscs claim 1 , comprising applying to said plants claim 1 , to the locus thereof claim 1 , or to plant propagation material thereof claim 1 , an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of a compound of formula I in . This application is a U.S. divisional ...

Inhibitors and methods of inhibiting bacterial and viral pathogens

Compounds, pharmaceutical compositions and methods for treating viral and bacterial infections, by administering certain thiourea compounds, specifically acylthiourea, carboximidoylthiourea and S-alkyl isothiourea derivatives and analogs, in therapeutically effective amounts are disclosed.

2-[[[2-[(HYDROXYACETYL)AMINO]-4-PYRIDINYL]METHYL]THIO]-N-[4-(TRIFLUOROMETHOXY)PHENYL]-3-PYRIDINECARBOXAMIDE BENZENESULFONATE, CRYSTAL OF SAME, CRYSTAL POLYMORPH THEREOF, AND METHODS FOR PRODUCTION THEREOF

In the course of developing 2-[[[2-[(hydroxyacetyl) amino]-4-pyridinyl] methyl] thio]-N-[4-(trifluoromethoxy) phenyl]-3-pyridinecarboxamide (compound A), there are the multiple problems: 1) compound A or its salt is difficult to be recrystallized, the storage stability largely differs depending on the kind of the salt, and it is very difficult to obtain a salt of compound A having excellent storage stability; 2) in a crystallization process of compound A, it is very difficult to control a crystal polymorph, and 3) compound A (free body) causes mineral deposition in the stomach when it is orally administered repeatedly. For solving these problems, we made examination focusing on the kind of the salt and, as a result, found that 1) benzenesulfonate of compound A does not decompose by light, humidity and other factors in a 1-week preliminary stability test (severe test), and has no problem in its storage stability, 2) a method of selectively producing two kinds of crystal forms of benzenesulfonate of compound A, and that 3) no mineral deposition in the stomach is observed even after a 4-week repeated oral administration. 1. A method of producing a so-called α-form crystal of benzenesulfonate of 2-[[[2-[(hydroxyacetyl) amino]-4-pyridinyl] methyl] thio]-N-[4-(trifluoromethoxy) phenyl]-3-pyridinecarboxamide , comprising the steps of: adding 2-[[[2-[(hydroxyacetyl) amino]-4-pyridinyl] methyl] thio]-N-[4-(trifluoromethoxy) phenyl]-3-pyridinecarboxamide to a good solvent solution containing benzenesulfonic acid; and sequentially adding a poor solvent to the reaction solution.2. A method of producing a so-called α-form crystal of benzenesulfonate of 2-[[[2-[(hydroxyacetyl) amino]-4-pyridinyl] methyl] thio]-N-[4-(trifluoromethoxy) phenyl]-3-pyridinecarboxamide , comprising the steps of: adding at least either of benzenesulfonic acid and its hydrate to a good solvent solution containing 2-[[[2-[(hydroxyacetyl) amino]-4-pyridinyl] methyl] thio]-N-[4-(trifluoromethoxy) phenyl]-3- ...

ETHYNYL DERIVATIVES

The present invention relates to ethynyl derivatives of formula I 2. A compound of formula I according to claim 1 , selected from the group consisting of:(1S,5R)-2-methyl-4-(5-(phenylethynyl)pyridin-2-yl)-2,4-diazabicyclo[3.2.0]heptan-3-one(1R,5S)-2-(5-((4-fluorophenyl)ethynyl)pyridin-2-yl)-4-methyl-2,4-diazabicyclo[3.2.0]heptan-3-one(1R,5S)-2-(5-((3-fluorophenyl)ethynyl)pyridin-2-yl)-4-methyl-2,4-diazabicyclo[3.2.0]heptan-3-one and(1R,5S)-2-(5-((2,5-difluorophenyl)ethynyl)pyridin-2-yl)-4-methyl-2,4-diazabicyclo[3.2.0]heptan-3-one.4. A pharmaceutical composition comprising a compound of and a therapeutically active carrier.5. A method for the treatment of anxiety and pain claim 1 , depression claim 1 , Fragile-X syndrome claim 1 , an autism spectrum disorder claim 1 , Parkinson's disease claim 1 , or gastro-esophageal reflux disease (GERD) in a patient claim 1 , which method comprises administering to the patient an effective amount of a compound as defined in . This application is a continuation of International Application PCT/EP2016/062202, filed May 31, 2016, which claims the benefit of priority to European Application 15170401.2, filed Jun. 3, 2015, each of which is incorporated herein by reference in its entirety.The present invention relates to ethynyl derivatives of formula Iwherein Ris hydrogen or F; n is 1 or 2 or to a pharmaceutically acceptable acid addition salt thereof.Preferred compounds are those wherein (R)is hydrogen, 3-fluoro, 4-fluoro or 2,5-difluoro.One embodiment of the present invention are compounds of formula I, for example the following:Other embodiments are described herein.It has now surprisingly been found that the compounds of general formula I are metabotropic glutamate receptor antagonists (NAM=negative allosteric modulators). Compounds with a similar main core have been generically described as positive allosteric modulators of the mGluR5 receptor. Surprisingly, it has been found that highly potent mGluR5 antagonists were obtained ...

Glucagon Receptor Modulators

The present invention provides a compound of Formula (I) 2. The compound of or a pharmaceutically acceptable salt thereof wherein Ris ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , isobutyl claim 1 , t-butyl claim 1 , pentyl claim 1 , neopentyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl or cyclopropylmethyl each optionally substituted with 1 to 3 fluoro and wherein said cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl are each optionally substituted with 1 to 2 methyl.3. The compound of or a pharmaceutically acceptable salt thereof wherein Ris 4-trifluoromethylphenyl or 4-chlorophenyl; and Rand Rat each occurrence are H.4. (R)-3-(6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinamido)propanoic acid or a pharmaceutically acceptable salt thereof.6. (S)-3-(6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinamido)propanoic acid or a pharmaceutically acceptable salt thereof.8. A pharmaceutical composition comprising (i) a compound of or a pharmaceutically acceptable salt thereof and (ii) a pharmaceutically acceptable excipient claim 1 , diluent claim 1 , or carrier.9. A method for treating obesity in a human comprising the step of administering to the human in need of such treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.10. A method for treating or delaying the progression or onset of Type 2 diabetes in a human comprising the step of administering to the human in need of such treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof. The present invention relates to compounds that are antagonists, mixed agonists/antagonists, partial agonists, negative allosteric modulators or inverse agonists of the glucagon receptor, pharmaceutical compositions comprising the compounds, and the uses of the compounds or compositions.Diabetes is a major public health ...

ASSAYS, METHODS AND MEANS

A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity. 155-. (canceled)56. A pharmaceutical composition comprising a HIF prolyl hydroxylase and a substrate of the hydroxylase are contacted under conditions in which the hydroxylase interacts with the substrate, in the presence or absence of a test substance; and', 'the interaction, or lack of interaction of, the hydroxylase and the substrate is determined by measuring the hydroxylase activity of the hydroxylase;', [{'sub': 'n', 'contains the sequence HXD[X]H, X being any amino acid and n being any number between 1 and 200,'}, 'contains a β-barrel jelly roll structure,', 'retains HIF prolyl hydroxylase activity, and', 'hydroxylates the proline residue of a motif LXXLXP contained in the substrate, where X is any amino acid; and, 'wherein the HIF prolyl hydroxylase is a fragment of SEQ ID NO: 4 that'}], 'a substance that has been identified as inhibiting the activity of a HIF hydroxylase in mediating the hydroxylation of one or more proline residues of a HIF-α protein by means of an assay method in which'}a pharmaceutically acceptable excipient.57. The pharmaceutical composition in claim 56 , wherein the fragment of SEQ ID NO: 4 used in the assay method has the HXD portion of the motif HXD[X]H on the second strand of the β-barrel jelly roll structure.58. The pharmaceutical composition in claim 57 , wherein the fragment of SEQ ID NO: 4 used in the assay method has the remaining H of the motif LXXLXP on or ...

ASSAYS, METHODS AND MEANS

A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the IIIF hydroxylase with a substrate. Modulators of IIIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity. 155-. (canceled)56. A pharmaceutical composition comprising a HIF prolyl hydroxylase and a substrate of the hydroxylase are contacted under conditions in which the hydroxylase interacts with the substrate, in the presence or absence of a test substance; and', 'the interaction, or lack of interaction of, the hydroxylase and the substrate is determined by measuring the hydroxylase activity of the hydroxylase;', [{'sub': 'n', 'contains the sequence HXD[X]H, X being any amino acid and n being any number between 1 and 200,'}, 'contains a β-barrel jelly roll structure,', 'retains HIF prolyl hydroxylase activity, and', 'hydroxylates the proline residue of a motif LXXLXP contained in the substrate, where X is any amino acid; and, 'wherein the HIF prolyl hydroxylase is a fragment of SEQ ID NO: 2 that'}], 'a substance that has been identified as inhibiting the activity of a HIF hydroxylase in mediating the hydroxylation of one or more proline residues of a HIF-α protein by means of an assay method in which'}a pharmaceutically acceptable excipient.57. The pharmaceutical composition in claim 56 , wherein the fragment of SEQ ID NO: 2 used in the assay method has the HXD portion of the motif HXD[X]H on the second strand of the β-barrel jelly roll structure.58. The pharmaceutical composition in claim 57 , wherein the fragment of SEQ ID NO: 2 used in the assay method has the remaining H of the motif LXXLXP on or ...

ASSAYS, METHODS AND MEANS

A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity. 155-. (canceled)56. A pharmaceutical composition comprising a HIF prolyl hydroxylase and a substrate of the hydroxylase are contacted under conditions in which the hydroxylase interacts with the substrate, in the presence or absence of a test substance; and', 'the interaction, or lack of interaction of, the hydroxylase and the substrate is determined by measuring the hydroxylase activity of the hydroxylase;', 'wherein the HIF prolyl hydroxylase has the amino acid sequence SEQ ID NO: 2; and, 'a substance that has been identified as inhibiting the activity of a HIF hydroxylase in mediating the hydroxylation of one or more proline residues of a HIF-α protein by means of an assay method in which'}a pharmaceutically acceptable excipient.57. The pharmaceutical composition of claim 56 , wherein the substance selectively inhibits the activity of HIF prolylhydroxylases.58. The pharmaceutical composition of claim 57 , wherein the substance selectively inhibits the activity of HIF prolyl hydroxylases relative to that of other 2-oxoglutarate dependent oxygenases.59. The pharmaceutical composition of claim 58 , wherein the other oxygenases are collagen prolyl hydroxylases (CPH).60. The pharmaceutical composition of claim 56 , wherein the substance is an inhibitor of a collagen prolyl hydroxylase or a modification thereof.61. The pharmaceutical composition of claim 56 , wherein the substance is a 2-oxoglutarate ...

ASSAYS, METHODS AND MEANS

A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the IIIF hydroxylase with a substrate. Modulators of IIIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity. 155-. (canceled)56. A method of treatment of a condition where a modulation in HIF levels is desirable by administering a substance that inhibits the hydroxylation of one or more proline residues of a human HIF-α protein mediated by a HIF hydroxylase , wherein that substance has been identified as inhibiting such hydroxylation by means of assays comprisingcontacting a HIF prolyl hydroxylase and a substrate of the hydroxylase under conditions in which the hydroxylase interacts with the substrate, in the presence or absence of a test substance; anddetermining the interaction, or lack of interaction of, the hydroxylase and the substrate by measuring the hydroxylase activity of the hydroxylase;wherein the HIF prolyl hydroxylase is chosen from (a) the amino acid sequence of SEQ ID NO: 2, 4, 6 or 8, FLJ21620 (BAB15101) or Clorf12 (NP071334); (b) a variant thereof having at least 60% identity to the amino acid sequence of SEQ ID NO: 2, 4, 6 or 8 and having HIF hydroxylase activity; or (c) a fragment of either (a) or (b) having HIF hydroxylase activity.57. The method of claim 56 , wherein the HIF hydroxylase used in the assays contains the sequence HXD[X]H claim 56 , X being any amino acid and n being any number between 1 and 200.58. The method of claim 57 , wherein the HIF hydroxylase used in the assays contains a β-barrel jelly roll structure.59. The method of claim 58 , wherein the HIF hydroxylase used ...

CARBOXAMIDES AS MODULATORS OF SODIUM CHANNELS

Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain. 4. The compound of or , or a pharmaceutically acceptable salt thereof , wherein L is O.5. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein each R is H.6. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H , halo , OH , C-Calkyl , or C-Calkoxy.7. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H or halo.8. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H or C-Calkyl.9. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H , halo , C-Calkyl , C-Chaloalkyl , or C-Calkoxy.10. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H , halo , C-Calkyl , C-Chaloalkyl , C-Calkoxy , C-Chaloalkoxy , or —W—(CH)—R.11. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H , halo , C-Calkyl , C-Chaloalkyl , C-Calkoxy , or —W—(CH)—R.12. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H or OCHPh.13. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H , halo , OH , C-Calkyl , C-Calkoxy , or —W—(CH)—R.14. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H , halo , OH , or C-Calkoxy.15. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H , halo , C-Calkoxy , or C-Chaloalkoxy.16. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris H , ...

Alpha 7 Nicotinic Acetylcholine Receptor Allosteric Modulators, Their Derivatives and Uses Thereof

The present application is related to compounds represented by Formula I, which are novel positive allosteric modulators of al nAChRs. The application also discloses the treatment of disorders that are responsive to enhancement of acetylcholine action on al nAChRs in a mammal by administering an effective amount of a compound of Formula I. 8. The compound of wherein:{'sup': 9', '12, 'Rand Rare hydrogen; and pharmaceutically acceptable salts and prodrugs thereof.'}9. The compound of wherein:{'sup': 17', '13, 'Xis CR;'}{'sup': 18', '14, 'Xis CR;'}{'sup': 19', '15, 'Xis CR;'}and pharmaceutically acceptable salts and prodrugs thereof.10. The compound of wherein:{'sup': 17', '13, 'Xis CR;'}{'sup': 18', '14, 'Xis CR;'}{'sup': '19', 'Xis N;'}and pharmaceutically acceptable salts and prodrugs thereof.11. The compound of wherein:{'sup': '17', 'Xis N;'}{'sup': 18', '14, 'Xis CR;'}{'sup': 19', '15, 'Xis CR;'}and pharmaceutically acceptable salts and prodrugs thereof.12. The compound of wherein:{'sup': 17', '13, 'Xis CR;'}{'sup': '18', 'Xis N;'}{'sup': 19', '15, 'Xis CR;'}and pharmaceutically acceptable salts and prodrugs thereof.14. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or prodrug thereof claim 1 , and a pharmaceutically acceptable carrier or diluent.15. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from:[2-(benzylamino)pyridin-3-yl](5-chloro-2,3-dihydro-1H-indol-1-yl)methanone (compound 1);(5-chloro-2,3-dihydro-1H-indol-1-yl)[2-(phenylamino)pyridin-3-yl]methanone (compound 2);(5-chloro-2,3-dihydro-1H-indol-1-yl)[2-[(pyridin-2-ylmethyl)amino]pyridin-3-yl]-methanone (compound 3);(5-chloro-2,3-dihydro-1H-indol-1-yl)[2-[(2-phenylethyl)amino]pyridin-3-yl]methanone (compound 4);(5-chloro-2,3-dihydro-1H-indol-1-yl)[2-[(pyridin-3-ylmethyl)amino]pyridin-3-yl]-methanone (compound 5);(5-chloro-2,3-dihydro-1H-indol-1-yl)[2-[[2-(pyridin-2-yl)ethyl]amino]-pyridin-3-yl]- ...

PYRIDYL BENZOTHIOPHENES AS KINASE INHIBITORS

This invention is directed to compounds, which are useful as protein kinase (PK) inhibitors and can be used to treat such diseases as cancer, blood vessel proliferative disorders, fibrotic disorders, mesangial cell proliferative disorders, metabolic diseases inflammatory disorders and neurodegenerative disorders. 2. (canceled)5. The compound according to claim 1 , wherein:{'sup': '1', 'Ris hydrogen;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris hydrogen;'}{'sup': 4', '4', '5, 'X is —N(R)C(O)N(RR);'}{'sup': 7', '6, 'Y is —C(O)—N═S(O)RR;'}{'sup': '7', 'sub': 1-8', '3, 'Ris Calkyl optionally substituted with one or more substituents selected from the group consisting of hydroxyl and —COOCH;'}{'sup': '6', 'sub': 1-8', '3, 'Ris Calkyl optionally substituted with one or more substituents selected from the group consisting of hydroxyl and —COOCH.'}6. The compound according to claim 1 , wherein:{'sup': '1', 'Ris hydrogen;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris hydrogen;'}{'sup': 4', '4', '5, 'X is —N(R)C(O)N(RR);'}{'sup': 7', '6, 'Y is —C(O)—N═S(O)RR;'}{'sup': '7', 'sub': 1-8', '3, 'Ris Calkyl optionally substituted with one or more substituents selected from the group consisting of hydroxyl and —COOCH;'}{'sup': '6', 'sub': 1-8', '3, 'Ris Calkyl optionally substituted with one or more substituents selected from the group consisting of hydroxyl and —COOCH; and'}{'sup': '11', 'Ris hydrogen.'}7. The compound according to claim 1 , wherein:{'sup': '1', 'Ris hydrogen;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris hydrogen;'}{'sup': 4', '4', '5, 'X is —N(R)C(O)N(RR);'}{'sup': '4', 'Ris hydrogen; and'}{'sup': 7', '6, 'Y is —C(O)—N═S(O)RR.'}8. The compound according to claim 1 , wherein:{'sup': '1', 'Ris hydrogen;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris hydrogen;'}{'sup': 4', '4', '5, 'X is —N(R)C(O)N(RR);'}{'sup': '4', 'Ris hydrogen;'}{'sup': 7', '6, 'Y is —C(O)—N═S(O)RR;'}{'sup': '7', 'sub': 1-8', '3, 'Ris Calkyl optionally substituted with one or more ...

AMIDE DERIVATIVES AS TTX-S BLOCKERS

The present invention relates to amide derivatives which have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved. 2. The compound described in whereinB is a chemical bond;or a prodrug thereof or a pharmaceutically acceptable salt thereof.4. The compound described in whereinZ is CH;or a pharmaceutically acceptable salt thereof.5. A compound according to wherein:{'sup': '1', 'sub': 3', '3', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2', '3, 'Ris selected from the group consisting of —CF, —OCF, —OCHCHF, —OCHC(CH)F, —CHCHCF, —OCFCHF, —OCFCF, —OCHCFCF, —OCHCFCHFand —OCHCF;'}{'sup': '2', 'Ris independently selected from the group consisting of(1) hydrogen, (2) halogen, (3) methyl, and (4) methoxy;p is 1;{'sup': '3', 'Ris hydrogen;'}{'sup': '4', 'Ris hydrogen or methyl;'}W is hydrogen;{'sup': '6', 'Ris selected from the group consisting of methyl, ethyl, isopropyl, and cyclopropyl;'}or a prodrug thereof or a pharmaceutically acceptable salt thereof.6. The compound as described in which is selected from:N-((2-acetamidopyridin-4-yl)methyl)-6-(2,2,2-trifluoroethoxyl)nicotinamide;N-((2-propionamidopyridin-4-yl)methyl)-6-(2,2,2-trifluoroethoxyl)nicotinamide;N-((2-(cyclopropanecarboxamido)pyridin-4-yl)methyl)-6-(2,2,2-trifluoroethoxyl)nicotinamide;N-((2-benzamidopyridin-4-yl)methyl)-6-(2,2,2-trifluoroethoxyl)nicotinamide;5-methyl-N-((2-propionamidopyridin-4-yl)methyl)-6-(2,2,2-trifluoroethoxyl)nicotinamide;5-chloro-N-((2-propionamidopyridin-4-yl)methyl)-6-(2,2,2-trifluoroethoxyl)nicotinamide;N-((2-propionamidopyridin-4-yl)methyl)-4-(2,2,2- ...

NOVEL CRYSTALLINE FORMS OF {[5-(3-CHLOROPHENYL)-3-HYDROXYPYRIDINE-2-CARBONYL] AMINO} ACETIC ACID AND PROCESSES FOR PREPARATION THEREOF

The present disclosure relates to novel crystalline forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl] amino} acetic acid and processes for preparation and uses thereof. Crystalline form CS1, form CS2 and form CS8 of the present disclosure can be used for preparing drugs treating anemia, which providing new choices for preparing drugs of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl] amino} acetic acid, and having very important value for drug development. 1. A crystalline form CS1 of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl] amino} acetic acid , wherein the X-ray powder diffraction pattern shows characteristic peaks at 2theta values of 13.9°±0.2° , 15.3°±0.2° , 15.6°±0.2° and 26.8°±0.2° using CuKα radiation.2. The crystalline form CS1 according to claim 1 , wherein the X-ray powder diffraction pattern shows one or more characteristic peaks at 2theta values of 17.0°±0.2° claim 1 , 19.1°±0.2° claim 1 , 23.5°±0.2° and 25.6°±0.2° using CuKα radiation.3. A process for preparing crystalline form CS1 according to claim 1 , wherein crystalline form CS1 can be obtained from either one of the following methods:1) Dissolving {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl] amino} acetic acid into ethers and then evaporating at room temperature to obtain solids; or2) Dissolving {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl] amino} acetic acid into tetrahydrofuran, and then adding water slowly into the solution or adding the solution into water; Stirring at room temperature for a period of time; Filtering and drying to obtain solids.4. The process for preparing crystalline form CS1 according to claim 3 , wherein said ether is methyl tert-butyl ether; said stirring time is 1-48 h.5. A crystalline form CS2 of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl] amino} acetic acid claim 3 , wherein the X-ray powder diffraction pattern shows characteristic peaks at 2theta values of 14.1°±0.2° claim 3 , 15.0°±0.2° and 18.3°±0.2° using CuKα radiation.6. The ...

PROCESS FOR PREPARING CRYSTALLINE SORAFENIB TOSYLATE

The present invention provides an industrially suitable process for the preparation of substantially pure 4-{4-[({[4-chloro-3-(trifluoromethyl)-phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide or Sorafenib and its tosylate salt, with a suitable impurity profile and without requirement of any additional purification steps. The present invention also provides Sorafenib base (II) as stable crystalline Form-SSB. 2. A process for the preparation of crystalline Sorafenib base-Form-SSB according to claim 1 , wherein the high boiling organic solvent is selected from Cketones or a mixture thereof.3. A process for the preparation of crystalline Sorafenib base-Form-SSB according to claim 1 , wherein Cketone is selected from methyl ethyl ketone (MEK) or methyl isobutyl ketone (MIBK).4. A process for the preparation of crystalline Sorafenib base-Form-SSB according to claim 1 , wherein reaction of 4-(4-aminophenoxy)-N-methylpicolinamide (III) with 4-chloro-3-(trifluoromethyl)phenylisocyanate (IV) claim 1 , is carried out at temperature ranging between 75-90° C.5. A process for the preparation of crystalline Sorafenib base-Form-SSB according to claim 1 , wherein crystalline Sorafenib base-Form-SSB obtained is characterized by X-ray powder diffraction pattern substantially according to and DSC isothermal pattern substantially according to .6. Crystalline Sorafenib base-Form-SSB claim 1 , characterized by X-ray powder diffraction pattern comprising at least 5 characteristic 2θ° peaks selected from the XRPD peak set of 9.9 claim 1 , 11.4 claim 1 , 12.6 claim 1 , 14.6 claim 1 , 15.2 claim 1 , 15.6 claim 1 , 18.1 claim 1 , 18.6 claim 1 , 21.8 claim 1 , 22.5 claim 1 , 22.9 claim 1 , 23.6 claim 1 , 24.8 claim 1 , 25.2±0.20 2θ° and DSC isotherm comprising a single endothermic peak ranging between 202 to 212° C.7. Crystalline Sorafenib base-Form-SSB according to claim 6 , characterized by X-ray powder diffraction pattern substantially according to and DSC isothermal ...

C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS

The present invention is directed to a compound represented by Structural Formula (A): 4. The compound of claim 3 , wherein Ris hydrogen or a (C-C)alkyl.5. The compound of claim 3 , wherein Ris selected from (C-C)alkyl claim 3 , (C-C)cycloalkyl(C-C)alkyl claim 3 , (C-C)alkoxy(C-C)alkyl claim 3 , phenyl claim 3 , phenyl(C-C)alkyl claim 3 , (C-C)cycloalkyl and halo(C-C)alkyl claim 3 , wherein each alkyl claim 3 , alkoxy and cycloalkyl moiety in the groups represented by Ris optionally substituted with one or more substituents independently selected from the group consisting of (C-C)alkyl and halo; and each phenyl moiety in the groups represented by Ris optionally substituted with one or more substituents independently selected from the group consisting of (C-C)alkyl claim 3 , halo claim 3 , (C-C)alkoxy claim 3 , (C-C)alkoxy(C-C)alkyl claim 3 , —CN claim 3 , halo(C-C)alkyl claim 3 , and halo(C-C)alkoxy.6. The compound of claim 3 , wherein Ris selected from hydrogen claim 3 , methyl and ethyl.7. The compound of claim 6 , wherein Ris selected from the group consisting of cyclopropyl claim 6 , cyclobutyl claim 6 , cyclopentyl claim 6 , cyclopropylmethyl claim 6 , cyclobutylmethyl claim 6 , phenyl claim 6 , benzyl claim 6 , —(CH)—O—CH claim 6 , —(CH)—OCH claim 6 , —C(CH) claim 6 , —CH(CH) claim 6 , —CHC(CH) claim 6 , —CHCH(CH) claim 6 , —CH—CF claim 6 , —(CH)—CHF claim 6 , and —(CH)CH; n is 0 claim 6 , 1 claim 6 , 2 claim 6 , 3 claim 6 , 4 claim 6 , 5 or 6; and wherein the phenyl or benzyl group represented by Ris optionally substituted with one or two substituents independently selected from the group consisting of (C-C)alkyl claim 6 , halogen claim 6 , (C-C)alkoxy claim 6 , (C-C)alkoxy(C-C)alkyl claim 6 , —CN claim 6 , halo(C-C)alkyl claim 6 , and halo(C-C)alkoxy.8. The compound of claim 7 , wherein Ris selected from cyclopropyl claim 7 , cyclopropylmethyl claim 7 , cyclobutyl claim 7 , cyclopentyl claim 7 , cyclohexyl claim 7 , —(CH)—O—CH claim 7 , —C(CH) claim 7 , —CH( ...

MARMELIN ANALOGS AND METHODS OF USE IN CANCER TREATMENT

A pharmaceutical composition can include: a marmelin analog compound, and a pharmaceutically acceptable carrier having the compound. The compound can be present in a therapeutically effective amount to treat or inhibit a disease state. The disease state can be cancer. The cancer can be selected from brain cancers, head and neck cancers, thyroid cancers, gastrointestinal cancers, esophageal cancers, stomach cancers, pancreatic cancers, liver cancers, colo-rectal cancers, lung cancers, kidney cancers, prostate cancers, bladder cancers, testicular cancers, breast cancers, ovarian cancers, cervical cancers, and melanomas. The carrier includes a cyclodextrin, which may form a complex with the compound. The compounds and compositions can be used to treat or inhibit progression of cancers. Colo-rectal, bladder, and prostate cancers are examples of some of the cancers that can be treated with the marmelin analog compounds. 2. The compound of claim 1 , wherein:{'sup': '2', 'Rincludes one or more of a hydrogen, halogens, hydroxyls, alkoxys, straight aliphatics, branched aliphatics, cyclic aliphatics, substituted aliphatics, unsubstituted aliphatics, saturated aliphatics, unsaturated aliphatics, aromatics, polyaromatics, substituted aromatics, hetero-aromatics, amines, primary amines, secondary amines, tertiary amines, aliphatic amines, thios, sulfhydryls, phosphors, carbonyls, carboxyls, amides, esters, amino acids, peptides, polypeptides, derivatives thereof, substituted or unsubstituted, or combinations thereof.'}3. The compound of claim 1 , wherein Rincludes one or more of hydrogen claim 1 , C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , C-Caryl claim 1 , C-Calkaryl claim 1 , C-Caralkyl claim 1 , halo claim 1 , hydroxyl claim 1 , sulfhydryl claim 1 , C-Calkoxy claim 1 , C-Calkenyloxy claim 1 , C-Calkynyloxy claim 1 , C-Caryloxy claim 1 , acyl claim 1 , C-Calkylcarbonyl (—CO-alkyl) claim 1 , C-Carylcarbonyl (—CO-aryl) claim 1 , acyloxy (—O-acyl) claim 1 , C- ...