ФУНГИЦИДНЫЕ ГИДРОКСИМОИЛТЕТРАЗОЛЬНЫЕ ПРОИЗВОДНЫЕ

Настоящее изобретение относится к гидроксимоилтетразольным производным формулы(I) ! ! где Т представляет тетразольный заместитель, А гетероцикл, L1 и L2 представляют различные линкерные группы, и Q представляет 6-членный гетероцикл, и их применению в качестве фунгицидных активных агентов, в частности в форме фунгицидных композиций, и способам борьбы с фитопатогенными грибками, особенно растений, используя указанные соединения или композиции. 4 н. и 13 з.п. ф-лы, 2 табл.

НОВЫЕ КОМПОЗИЦИИ И СПОСОБЫ КОНТРОЛЯ НЕМАТОД КАК ВРЕДИТЕЛЕЙ СЕЛЬСКОГО ХОЗЯЙСТВА

Изобретение относится к соединениям Формулы I или его пестицидно приемлемым солям. Соединения Формулы I могут быть полезны для борьбы с паразитарными нематодами растений. В Формуле IА является необязательно замещенным фенилом или пиридилом, при этом указанные заместители выбраны из группы, состоящей из СН, CF, F, Cl, Br, ОСНи CN; С является гетероарилом, выбранным из группы, состоящей из 3-тиенила и 3-фуранила, каждый из которых независимо может быть необязательно замещен одним или более заместителей, выбираемых из группы, состоящей из: F, Cl, Br и СН, или С выбран из группы, состоящей из 1-пирролидинила, 1-пирролила и 2-пирролила, каждый из которых может быть необязательно независимо замещен одним или более заместителем, выбранным из группы, состоящей из метила и галогена. Изобретение также относится к соединениям формулы II или его пестицидно приемлемым солям, и к способам борьбы с паразитарными нематодами растений. Технический результат: получены новые соединения, обладающие нематицидной ...

ПРОИЗВОДНОЕ ТЕТРАЗОЛИЛГИДРОКСИИМИНА, СПОСОБ ЕГО ОЧИСТКИ И СПОСОБ ЕГО ПОЛУЧЕНИЯ

Изобретение относится к соединению, представленному общей формулой (I)где n представляет собой 0, Y представляет собой алкильную группу, имеющую от 1 до 6 атомов углерода, М представляет собой щелочной металл или щелочноземельный металл, a m представляет собой целое число от 1 или 2. Также изобретение относится к способу получения соединения общей формулы (I), к способу очистки (Z) формы соединения общей формулы (I) и к способу получения (Z) формы соединения общей формулы (I). Технический результат: получены новые соединения общей формулы (I), которые могут использоваться в качестве промежуточного продукта в синтезе производного тетразолилоксима. 4 н. и 5 з.п. ф-лы, 1 табл., 5 пр.

НОВЫЕ ПРОИЗВОДНЫЕ ТЕТРАЗОЛА И ИХ ПРИМЕНЕНИЕ В ЛЕЧЕНИИ ТУБЕРКУЛЕЗА

Изобретение относится к соединению формулы (I) или его фармацевтически приемлемой соли, где Х является СН или N; n равно 0, 1 или 2; R1 представляет метил, этил, цианометил, С-связанный ацетамидо, метилацетат, 2-гидроксиэтил, 2-гидрокси-1-пропил, 1,3-дигидрокси-2-пропил или 1,2-дигидрокси-3-пропил; R2 независимо выбран из атома галогена, C1-2 алкила или C1-2 алкокси; R3 представляет фенил, пиридил, пиримидинил, пиразинил или пиридазинил, где каждая из этих групп может быть необязательно замещена одним или двумя заместителями, выбранными из атома галогена, циано, C1-2 алкила, необязательно замещенного не более чем тремя атомами фтора, и C1-2 алкокси, необязательно замещенного не более чем тремя атомами фтора, где заместители могут быть одинаковыми или различными; или R3 представляет циклогексил, который может быть необязательно замещен одним или двумя атомами фтора или хлора, где каждый заместитель может быть присоединен к одному и тому же атому углерода и каждый заместитель может быть одинаковым ...

ПРОИЗВОДНЫЕ 5-ЙОДТЕТРАЗОЛА, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФУНГИЦИДНОЕ СРЕДСТВО НА ИХ ОСНОВЕ, ДИСПЕРСНЫЕ ЛАКОКРАСОЧНЫЕ МАТЕРИАЛЫ, СОДЕРЖАЩИЕ ИХ, СПОСОБ ЗАЩИТЫ РАСТЕНИЙ И ДИСПЕРСНЫХ ЛАКОКРАСОЧНЫХ МАТЕРИАЛОВ ОТ ПОРАЖЕНИЯ И/ИЛИ РАЗРУШЕНИЯ ГРИБКАМИ

Изобретение относится к области борьбы с грибками, конкретно к производным 5-йодтетразола ! ! в которой R1 означает бутилен, неразветвленный незамещенный алкил с 8-16 атомами углерода, неразветвленный или разветвленный незамещенный или однократно или многократно, одинаково или по-разному замещенный алкил с 1-8 атомами углерода, причем заместители однократно или многократно, одинаково или по-разному замещенных алкильных остатков выбраны из группы, включающей незамещенный алкокси с 1-6 атомами углерода и алкокси с 1-6 атомами углерода, замещенный диоксалонилом, фенил, который до пяти раз одинаково или по-разному замещен галогеном, алкилом с 1-4 атомами углерода, галогеналкилом с 1-4 атомами углерода, алкокси с 1-3 атомами углерода, алкилтио с 1-4 атомами углерода, морфолинилом, за исключением следующих соединений: 1-трет-бутил-5-йодтетразол, 1-этил-5-йодтетразол, 1-метил-5-йодтетразол. Данные производные 5-йодтетразола получают за счет того, что тетразолы общей формулы (II) ! , ! в которой ...

ИНГИБИТОРЫ НЕПРИЛИЗИНА

Изобретение относится к соединениям, характеризующимся формулой XII, где значения R, R, R, Rи X определены в формуле изобретения, или к их фармацевтически приемлемой соли. Соединение по изобретению обладает ингибирующей активностью в отношении неприлизина (NEP) и предназначено для получения лекарственного средства для лечения гипертензии, сердечной недостаточности или заболевания почек. 7 н. и 21 з.п. ф-лы, 11 пр.

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Изобретение относится к новым производным диариловой кислоты формулы (Ia) где представляет собой хинолинил или оксазолил, замещенный фенилом и необязательно замещенный галогеном, причем указанный фенил может быть замещен алкоксигруппой или галогеном; а = 1; b = 0 или 1; R1, R2, R3, R4 представляют собой водород; А представляет: R5, R6, R7, R8, R15, R16 представляют собой водород; с = 0; d = 0; g = целое число от 1 до 5; В и E представляют химическую связь; Z представляет собой HOOC-; R' и R" являются кольцевыми заместителями, более предпочтительно R' является водородом, алкокси, бензилокси, арилокси или фенилом; и R" является низшим алкилом или алкокси, и к их фармацевтически приемлемым солям. Изобретение также относится к фармацевтической композиции, обладающей активностью агониста или антагониста PPAR рецептора, на основе этих соединений. Технический результат - получение новых соединений формулы Ia и фармацевтической композиции на их основе в целях лечения заболеваний, которые можно ...

ИНГИБИТОРЫ ЦИСТАТИОНИН-γ-ЛИАЗЫ (CSE)

Изобретение относится к новым соединениям формулы (I) и формулы (IV) или их фармацевтически приемлемым солям, которые ингибируют цистатионин-γ-лиазу (CSE). Соединения могут быть использованы для лечения или предупреждения или снижения числа случаев состояния, выбранного из ноцицептивной боли, острой послеоперационной боли, нейропатической боли, невралгии тройничного нерва (тригеминальной невралгии), диабетической периферической нейропатии, герпетической невралгии, постгерпетической невралгии, воспалительной боли, смешанной боли нейропатического и воспалительного характера, ревматоидного артрита, воспалительного заболевания кишечника, синдрома раздраженного кишечника, остеоартрита, острого панкреатита, хронического панкреатита, боли, ассоциируемой с острым панкреатитом, боли, ассоциируемой с хроническим панкреатитом, мигрени, подагры, анкилозирующего спондилоартрита, системной красной волчанки (SLE), синдрома системного воспалительного ответа (SIRS), синдрома полиорганной дисфункции (MODS ...

МОДУЛЯТОРЫ СВЯЗАННЫХ С MAS РЕЦЕПТОРОВ G-БЕЛКА X4 И СВЯЗАННЫЕ С НИМИ ПРОДУКТЫ И СПОСОБЫ

Изобретение относится к соединению, имеющему одну из следующих структур, или его фармацевтически приемлемой соли: Соединение № Структура 1-55 1-78 5-1 4-10 1-65 4-11 1-58 1-56 9-1 1-82 1-85 1-29 1-101 2-3 1-103 1-112 4-7 11-1 Изобретение также относится к фармацевтической композиции и способу лечения MRGPR X4-зависимых состояний на основе указанного соединения. Технический результат: получено новое соединение и фармацевтическая композиция на его основе, которые могут найти применение в медицине для лечения MRGPR X4-опосредованных заболеваний. 4 н. и 35 з.п. ф-лы, 7 ил., 70 табл., 70 пр.

ИНГИБИТОРЫ НЕПРИЛИЗИНА

Изобретение относится к соединению формулы I, где Rпредставляет собой -OR; Rпредставляет собой Н; X выбран из пиразола, триазола, бензотриазола, тетразола, оксазола, изоксазола, тиазола, пиридазина, пиримидина и пиридилтриазола; Rотсутствует или выбран из Н; галогена; -Салкилен-ОН; -Салкила; -Сциклоалкила; -Салкилен-О-Салкила; -C(O)R; -Салкилен-COOR; -С(О)NRR; -NHC(O)R; =O; фенила, необязательно замещенного одной или двумя группами, независимо выбранными из галогена, -ОСН, -NHC(O)CHи фенила; нафталенила; пиридинила; пиразинила; и R, когда он присутствует, соединен с атомом углерода; Rвыбран из Н; -ОН; -Cалкилен-COOR; -пиридинила; и фенила или бензила, необязательно замещенного одной или более группами, выбранными из галогена и -ОСН; и R, когда он присутствует, соединен с атомом углерода или атомом азота; а равен 0; или а равен 1; и Rвыбран из галогена и -CN; b равен 0; или b равен 1, и Rвыбран из Cl, F, -ОН, -СН, -ОСНи -CF; или b равен 2, и Rкаждый независимо выбран из галогена, -ОН, -СН ...

ФАРМАЦЕВТИЧЕСКИЕ КОМБИНАЦИИ АНТАГОНИСТА РЕЦЕПТОРА АНГИОТЕНЗИНА И ИНГИБИТОРА NEP

Изобретение относится к соединению двойного действия, характеризующегося суммарной формулой [((S)-N-валерил-N-{[2'-(1Н-тетразол-5-ил)бифенил-4-ил]метил}валин)этиловый эфир (2R,4S)-5-бифенил-4-ил-4-(3-карбоксипропиониламино)-2-метилвалериановой кислоты]Na·xHO в твердой форме, где x равен от 0 до 3, которое является антагонистом рецептора ангиотензина и ингибитора NEP, и может быть использовано для лечения гипертензии. 6 н. и 13 з.п. ф-лы, 1 табл., 4 пр.

ИНГИБИТОРЫ ПРОДУЦИРОВАНИЯ / СЕКРЕЦИИ β-АМИЛОИДНОГО БЕЛКА

Описывается соединение общей формулы (3): где R15 представляет гетероциклическую группу, выбранную из 3-7-членной насыщенной или 4-7-членной ненасыщенной моноциклической гетероциклической группы, имеющей 1-4 атома, выбранных из атома азота, атома кислорода и атома серы, или 7-14-членной полициклической гетероциклической группы, имеющей 1-4 атома, выбранных из атома азота, атома кислорода и атома серы, которая может иметь заместитель; R16представляет циклоалкильную группу, имеющую 3-7 атомов углерода, моноциклическую ароматическую углеводородную группу, имеющую 6-14 атомов углерода, или гетероциклическую группу, выбранную из 3-7-членной насыщенной или 4-7-членной ненасыщенной моноциклической гетероциклической группы, имеющей 1-4 атома, выбранных из атома азота, атома кислорода и атома серы, которая может иметь заместитель; R17представляет моноциклическую ароматическую углеводородную группу, имеющую 6-14 атомов углерода, или гетероциклическую группу, выбранную из 4-7-членной ненасыщенной ...

АНАЛОГИ CYP-ЭЙКОЗАНОИДОВ ДЛЯ ПРИМЕНЕНИЯ В ЛЕЧЕНИИ ИЛИ ПРЕДОТВРАЩЕНИИ НАРУШЕНИЯ, СВЯЗАННОГО С НЕОВАСКУЛЯРИЗАЦИЕЙ И/ИЛИ ВОСПАЛЕНИЕМ

Изобретение относится к применению соединения формулы (I) или его фармацевтически приемлемой соли, которые являются метаболически устойчивыми аналогами биологически активных липидных медиаторов, образующихся из полиненасыщенных жирных кислот омега-3 (ПНЖК n-3), для лечения, снижения риска развития или предотвращения нарушения, связанного с неоваскуляризацией и/или воспалением. Технический результат: лечение, снижение риска развития или предотвращение нарушения, связанного с неоваскуляризацией и/или воспалением. В общей формуле (I) P представляет собой группу, представленную общей формулой (II), E представляет собой группу, представленную общей формулой (III) или (IV), I представляет собой -(CH2)m-Y. Остальные значения переменных указаны в формуле изобретения. 14 з.п. ф-лы, 5 ил., 7 табл., 5 пр. P-E-I (I) -(CH2)n-O-(CH2)k-X (II), ...

ПРОИЗВОДНЫЕ FGF21 СО СВЯЗУЮЩИМ АЛЬБУМИНА А-В-С-D-E- И ИХ ПРИМЕНЕНИЕ

Изобретение относится к фактору роста фибробластов 21 (FGF21), более конкретно к производным соединений FGF21, имеющим ковалентно присоединенное связующее альбумина формулы A-B-C-D-E-, и их фармацевтическому применению, в частности, для лечения диабета, дислипидемии, ожирения, сердечно-сосудистых заболеваний, метаболического синдрома и/или неалкогольной жировой болезни печени (НАЖБП). Производные по настоящему изобретению обладают пролонгированным действием, например способны поддерживать низкий уровень глюкозы в течение более длительного периода времени, способны к увеличению времени полувыведения in vivo FGF21 и/или приводят в результате к более низкому клиренсу FGF21. Производные по изобретению предпочтительно обладают улучшенной устойчивостью к окислению. 3 н. и 7 з.п. ф-лы, 4 табл., 58 пр.

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 ...

СОЕДИНЕНИЯ, ОБЛАДАЮЩИЕ ИЗБИРАТЕЛЬНОСТЬЮ В ОТНОШЕНИИ РЕЦЕПТОРОВ РЕТИНОИДА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ (ВАРИАНТЫ), СПОСОБ МОДУЛИРОВАНИЯ ПРОЦЕССОВ (ВАРИАНТЫ), СПОСОБ ПОДАВЛЕНИЯ ПАТОЛОГИЧЕСКИХ СОСТОЯНИЙ

Описываются новые соединения общей формулы (I), где значения R1-R5, R14, Q и n указаны в п. 1 формулы, обладающие избирательной активностью в отношении специфических рецепторов ретиноевой кислоты; они могут найти применение при ле чении различных патологических состояний. Описываются фармацевтические композиции на основе соединений формулы (I), способ подавления патологических состояний, а также способ модулирования процессов (варианты). 6 с. и 20 з.п.ф-лы, 12 ил., 6 табл.

ПРОИЗВОДНЫЕ ТЕТРАЗОЛА, СПОСОБ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ИНГИБИРУЮЩАЯ АЛЬДОЗОРЕДУКТАЗУ

Использование: в медицине в качестве лекарственного средства для диабетических осложнений. Сущность изобретения: производные тетразола общей формулы: где A - алкиленовая группа, имеющая -1-4 атома углерода; R1 - водород или низшая алкильная группа, R2 - водород, гидрокси, галоид, карбокси C1-7 алкил, амидо, амино, C1-7 алкокси, фенил, фенилокси, низший алкилтио, низший алкилсульфинил, низший алкилсульфонил, нитрогруппа или группа формулы: NHCOCOOR5, где R5 - водород или низший алкил, моно- или ди/низший/алкиламиносульфонил или группа формулы: где A и R1 имеют указанные выше значения, R3 - водород, галоид, нитро, C1-7 алкил, C1-7 алкокси или гидрокси; R4 - водород, C1-7 алкил, C1-7 алкокси или группа -NHCOCOOR5, где R5 имеет указанные выше значения, при условии, что соединение формулы I не включает следующей комбинации заместителей; где A - метиленовая группа, R2, R3 и R4 - атомы водорода, и R1 - атом водорода, метильная группа или этильная группа; где A - этилиденовая группа, R2, R3 и R4 ...

ПРОИЗВОДНЫЕ ГИДРАЗИНА ИЛИ ИХ СОЛИ, ФАРМАЦЕВТИЧЕСКОЕ СРЕДСТВО, АМИНОАЛКИЛГИДРАЗИНЫ ИЛИ ИХ СОЛИ

Использование: в медицине как обладающие свойством ингибировать действие фермента ВИЧ- протеазы и антивирусной активностью. Сущность изобретения: производные гидразина общей формулы 1: R1R2N - C(R3 R4) - C(R5R6 - N(R7)N(R8R9) , где R1 и R9 независимо друг от друга - водород, низший алканоил, фенил(низш.) алканоил, фенил(низш). алканоил, в котором остаток низшего алконоила замещен карбамоилом, морфолино(низш.) алканоил, тиоморфолино(низш.) алканоил, пиридил(низш.) алканоил, хинолил(низш.) алканоил, тетразолил(низш. ) алканоил, амино(низш. ) алканоил, замещенный у аминного азота N-морфолино- или N-тиоморфолинокарбон - ил, галоген(низш.) алканоил, содержащий до трех атомов галогена, 2-(N-морфолино(низш.) алкилкарбамоил)-низший алканоил, 2-(N-пиридил(низш. ) алкилкарбамоил)-низший алканоил, низший алкоксикарбонил, фенил(низш. ) алкоксикарбонил, тетрагидрофуранил(низш.) алкилксикарбонил, низший алкилсульфонил, N-пиридил(низш.) алкил-N-(низш.) алкилкарбамоил, или ацильный остаток аминокислоты ...

2,5- ИЛИ 2,6-ДИЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ ГИДРОХИНОНА, СОДЕРЖАЩИЕ ПО КРАЙНЕЙ МЕРЕ ОДНУ КАРБОКСИ-, СУЛЬФО- ИЛИ АМИДОГРУППУ, ПРИМЕНЯЕМЫЕ В КАЧЕСТВЕ ЛЕКАРСТВЕННЫХ СРЕДСТВ

Изобретение относится к новым производным гидрохинона формулы (I), где Ra, Rb, R1-R3 определены в формуле изобретения, промежуточным соединениям для получения производных гидрохинона формулы (I), а также фармацевтическим композициям для применения в лечении и/или предотвращения, например, аутоиммунных, иммунологических, ревматологических, сосудистых, офтальмологических, фиброзных, метаболических и желудочно-кишечных расстройств, нейровоспалительных и нейродегенеративных заболеваний, новообразований и связанных с раком заболеваний, гормональных заболеваний и иммунологических нарушений, возникающих в результате вирусных и бактериальных инфекционных заболеваний и их осложнений. 4 н. и 15 з.п. ф-лы, 11 ил., 59 табл., 5 пр.

2-[(4-ГЕТЕРОЦИКЛ-ФЕНОКСИМЕТИЛ)ФЕНОКСИ]-АЛКАНОАТЫ, ГЕРБИЦИДНАЯ КОМПОЗИЦИЯ, СПОСОБ ПОДАВЛЕНИЯ НЕЖЕЛАТЕЛЬНОЙ РАСТИТЕЛЬНОСТИ

Обладающие гербицидной активностью новые 2-(/4-гетероцикл-феноксиметил/фенокси)-алканоаты общей формулы I, приведенной в формуле изобретения, где Q - 4-дифторметил-4,5-дигидро-3-метил-1,2,4-триазол-5/1H/-OH-1-ил, или 1-метил-6-трифторметил-2, 4-/1H, 3H/-пиримидиндион-3-ил; A - группа формулы RO-C(О)-C(R1)H-, где R' - H, CH3, R - H, низший алкил, незамещенный или замещенный хлором, или группа -(CHR7 - CH2 - O)nR8, где R7 - H или метил; R8 - низший алкил; n - 1 или 2; X - H, метил, F или Cl; W - O или S; Z - H, F, Cl, Br, низший алкил или метокси; Z' - H, F или Cl; или Z и Z' - взятые вместе могут представлять собой -(CH2)4 - для образования тетрагидронафтильной группы, используют в создании гербицидной композиции, которую применяют в способе борьбы с нежелательной растительностью. 3 с. и 17 з.п. ф-лы, 5 табл.

ЗАМЕЩЕННЫЕ БЕНЗОИЛЦИКЛОГЕКСЕНОНЫ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ГЕРБИЦИДНОГО СРЕДСТВА

... 1. Соединения формулы (I) в которой Q представляет собой О (кислород) или S (серу), R1 представляет собой водород, галоген или соответственно, при необходимости, замещенный алкил, алкилтио или арил, R2 представляет собой водород, галоген или, при необходимости, замещенный алкил, или вместе с R1 представляет собой O (кислород) или алкандиил (алкилен), R3 представляет собой водород, нитро, циано, карбокси, карбамоил, тиокарбамоил, галоген или соответственно, при необходимости, замещенный алкил, алкокси, алкилтио, алкилсульфинил, алкилсульфонил, алкиламино, диалкиламино, диалкиламино-карбонил или диалкиламиносульфонил, R4 представляет собой водород, нитро, циано, карбокси, карбамоил, тиокарбамоил, галоген или соответственно, при необходимости, замещенный алкил, алкокси, алкилтио, алкилсульфинил, алкилсульфонил, алкиламино, диалкиламино, диалкиламино-карбонил или диалкиламиносульфонил, R5 представляет собой водород или соответственно, при необходимости, замещенный алкил, алкокси, алкилтио, ...

ПРОИЗВОДНЫЕ 2-ФЕНОКСИ И 2-ФЕНИЛСУЛЬФОНАМИДА С ССR3 АНТАГОНИСТИЧЕСКОЙ АКТИВНОСТЬЮ ДЛЯ ЛЕЧЕНИЯ АСТМЫ И ДРУГИХ ВОСПАЛИТЕЛЬНЫХ ИЛИ ИММУНОЛОГИЧЕСКИХ ЗАБОЛЕВАНИЙ

... 1. Производное бензолсульфонамида, имеющее формулу (I), его таутомерные и стереоизомерные формы и его соли где Х представляет О или S; R1 представляет водород, галоген, гидрокси, нитро, циано, С1-6алкоксикарбонил, амино, С1-6алкиламино, ди(С1-6алкил)амино, С1-6алканоил, фенил, С1-6алкил, необязательно замещенный одним, двумя или тремя галогенами, или С1-6алкокси, необязательно замещенный одним, двумя или тремя галогенами; R2 представляет водород, галоген, гидрокси, нитро, циано, С1-6алкоксикарбонил, С1-6алкиламино, ди(С1-6алкил)амино, С1-6 алканоил, фенил, С1-6алкил, необязательно замещенный одним, двумя или тремя галогенами, или С1-6алкокси, необязательно замещенный одним, двумя или тремя галогенами; R3 представляет водород, галоген, гидрокси, нитро, циано, амино, карбокси, тетразолил, С1-6алкокси, С1-6алкоксикарбонил, С1-6алканоил, С1-6 алканоиламино, С1-6алкил, необязательно замещенный одним, двумя или тремя галогенами или гидрокси; R4 представляет или где R40 представляет С1-6алкил, ...

АРИДЗАМЕЩЕННЫЕ ПИПЕРАЗИНОВЫЕ ПРОИЗВОДНЫЕ

... 1. Соединение формулы или его фармацевтически приемлемая соль, где V отсутствует или представляет собой -(С=O)-; W представляет собой N, СН или С-ОН; Y1, Y3, Y4, и Y5 независимо представляют собой CR1 или азот; Z представляет собой азот или CR2; каждый R1 независимо представляет собой (i) водород, галоген, гидрокси, нитро, циано, амино, аминокарбонил, C1-С6алкил, С2-С6алкенил, С3-С6алкинил, C1-С6алкокси, галогенС1-С6алкил, галогенС1-С6алкокси, гидроксиС1-С6алкил, (С1-С4алкокси)С1-С4алкил, C1-С6алкилтио, аминоС1-С6алкил, моно- или ди-(С1-С6алкил)аминоС0-С6алкил, моно- или ди-(С1-С6алкил)аминокарбонил, (С3-С7циклоалкил)С0-С6алкил, или (от 4- до 7-членный гетероциклоалкил)С0-С6алкил; или (ii) взятый вместе с R2 образует конденсированный 5- или 6-членный карбоцикл или гетероцикл, каждый из которых является замещенным 0-3 заместителями, независимо выбранными из галогена, гидрокси, нитро, циано, амино, С1-С4алкил, С1-С4 алкокси, галогенС1-С4алкил и галогенС1-С4алкокси; R2 представляет собой галоген ...

ЛЕКАРСТВЕННЫЕ СРЕДСТВА ДЛЯ ЛЕЧЕНИЯ ПОВТОРЕНИЯ ГИПЕРТЕНЗИИ С ГИПЕРУРИКЕМИЕЙ И/ИЛИ ГИПЕРХОЛЕСТЕРИНЕМИЕЙ

... 1. Лекарственные средства для лечения повторения гипертензии с сывороточной гиперурикемией и/или гиперхолестеринемией, действующим началом которых являются 2-пропил-3-{[2'-(1H-тетразол-5-ил)бифенил-4-ил]метил}-5,6,7,8-тетрагидроциклогептаимидазол-4-(3Н)-он и его пролекарства или соли. 2. Лекарственные средства для лечения повторения гипертензии с сывороточной гиперурикемией, действующим началом которых являются 2-пропил-3-{[2'-(1H-тетразол-5-ил)бифенил-4-ил]метил}-5,6,7, 8-тетрагидроциклогептаимидазол-4-(3Н)-он и его пролекарства или соли вместе с диуретиками. 3. Лекарственные средства для лечения повторения гипертензии с сывороточной гиперурикемией по п.2, где диуретики представляют собой один или несколько диуретиков, выбранных из группы, состоящей из диуретиков сульфонамидного типа, диуретиков типа феноксиуксусной кислоты, тиазидного типа, триамтерена, амилорида, спиронолактона, канреноата калия и траксанокса натрия. 4. Лекарственные средства для лечения повторения гипертензии с сывороточной ...

АЛЬФА-(ТРИФТОРМЕТИЛЗАМЕЩЕННЫЕ АРИЛОКСИ, АРИЛАМИНО, АРИЛТИО ИЛИ АРИЛМЕТИЛ)ТРИФТОРМЕТИЛЗАМЕЩЕННЫЕ ФЕНИЛУКСУСНЫЕ КИСЛОТЫ И ПРОИЗВОДНЫЕ КАК ПРОТИВОДИАБЕТИЧЕСКИЕ СРЕДСТВА

... 1. Соединение формулыгде Х представляет собой элемент, выбранный из группы, состоящей из О, S, SO, SO, CHR и NR, где R представляет собой Н, (C-C)-алкил, COR, COORи CONRR, где Rи Rвыбирают, каждый независимо, из группы, состоящей из Н и (С-С)-алкила;Y представляет собой элемент, выбранный из группы, состоящей из CHOR, COR, тетразола, СНО, CONRR, CH(=NR) и CH(=NOR), где Rпредставляет собой элемент, выбранный из группы, состоящей из Н, (С-С)-алкила, (С-С)-алкенила, (С-C)-алкинила, (С-С)-циклоалкила, (С-С)-циклоалкилалкила, арила, арил-(С-С)-алкила и (С-С)-алкилен-Z, где Z выбирают из группы, состоящей из COR, COOR, NRR, NRCONRR, NRCOR, NRCOORи CONRR, где R, Rи Rвыбирают, каждый независимо, из группы, состоящей из Н, (C-C)-алкила и фенила, или, необязательно, два элемента из числа R, Rи R, когда они присоединены к одному и тому же атому азота, объединяются с образованием пяти- или шестичленного цикла; и где Rвыбирают из группы, состоящей из Н, (С-С)-алкила, арила и ОН, и Rи R, необязательно ...

НОВОЕ СУЛЬФОНАМИДНОЕ ПРОИЗВОДНОЕ МАЛОНОВОЙ КИСЛОТЫ И ЕГО ФАРМАЦЕВТИЧЕСКОЕ ПРИМЕНЕНИЕ

... 1. Производное сульфонилмалонамида, представленное следующей формулой (I) ! ! где R1 представляет собой необязательно замещенный C1-8 алкил, необязательно замещенный C2-6 алкенил, необязательно замещенный C2-6 алкинил, необязательно замещенный C3-10 циклоалкил, необязательно замещенный C3-10 циклоалкил C1-6 алкил, необязательно замещенный гетероцикл, необязательно замещенный арил, необязательно замещенный арил C1-6 алкил, необязательно замещенный арилокси C1-6 алкил, необязательно замещенный арил C2-6 алкенил, необязательно замещенный гетероарил, необязательно замещенный гетероарил C1-6 алкил, необязательно замещенный гетероарилокси C1-6 алкил или необязательно замещенный гетероарил C2-6 алкенил; ! один из R2 и R3 представляет собой атом водорода или атом галогена, а другой представляет собой атом галогена, необязательно замещенный C1-6 алкил, необязательно замещенный C1-6 алкокси, необязательно замещенный C2-6 алкенил, необязательно замещенный C2-6 алкинил, -(CH2)n-С(O)-NR5R6 (где n представляет ...

ПРОИЗВОДНЫЕ ТРИАМИНОПИРИМИДИНЦИКЛОБУТЕНДИОНА В КАЧЕСТВЕ ИНГИБИТОРОВ ФОСФАТАЗЫ CDC25

... 1. Соединение общей формулы (I): ! ! в рацемической форме, энантиомерной форме или любой комбинации этих форм, ! в котором Y означает независимо радикал NR1R2 или OR13; ! W означает независимо -NR6- или -CR6R7; ! R3 означает атом водорода или алкильный радикал; ! n и m означают целые числа, составляющие от 0 до 4 включительно; ! R4a и R5a означают независимо атом водорода, алкильный радикал или же вместе с атомом азота, к которому они присоединены, образуют гетероциклоалкил; ! R4b и R5b означают независимо атом водорода, алкильный радикал или же вместе с атомом азота, к которому они присоединены, образуют гетероциклоалкил; ! R1, R2 и R13 означают независимо атом водорода или радикал, выбираемый из: ! - алкила; ! - арилалкила, возможно замещенного одним или несколькими, одинаковыми или разными галоген-радикалами; !- гетероарила, возможно замещенного одним или несколькими, одинаковыми или разными радикалами, выбираемыми из: галогена, гидроксила, цианогруппы, нитрогруппы, алкила, алкоксила ...

ПРОИЗВОДНЫЕ 5-ЙОДТЕТРАЗОЛА, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФУНГИЦИДНОЕ СРЕДСТВО НА ИХ ОСНОВЕ, ДИСПЕРСНЫЕ ЛАКОКРАСОЧНЫЕ МАТЕРИАЛЫ, СОДЕРЖАЩИЕ ИХ, СПОСОБ ЗАЩИТЫ РАСТЕНИЙ И ДИСПЕРСНЫХ ЛАКОКРАСОЧНЫХ МАТЕРИАЛОВ ОТ ПОРАЖЕНИЯ И/ИЛИ РАЗРУШЕНИЯ ГРИБКАМИ

Изобретение относится к области борьбы с грибками, конкретно к производным 5-йодтетразола ! ! в которой R1 означает бутилен, неразветвленный незамещенный алкил с 8-16 атомами углерода, неразветвленный или разветвленный незамещенный или однократно или многократно, одинаково или по-разному замещенный алкил с 1-8 атомами углерода, причем заместители однократно или многократно, одинаково или по-разному замещенных алкильных остатков выбраны из группы, включающей незамещенный алкокси с 1-6 атомами углерода и алкокси с 1-6 атомами углерода, замещенный диоксалонилом, фенил, который до пяти раз одинаково или по-разному замещен галогеном, алкилом с 1-4 атомами углерода, галогеналкилом с 1-4 атомами углерода, алкокси с 1-3 атомами углерода, алкилтио с 1-4 атомами углерода, морфолинилом, за исключением следующих соединений: 1-трет-бутил-5-йодтетразол, 1-этил-5-йодтетразол, 1-метил-5-йодтетразол. Данные производные 5-йодтетразола получают за счет того, что тетразолы общей формулы (II) ! ! в которой ...

ИНГИБИТОРЫ 11БЕТА-ГИДРОКСИСТЕРОИДДЕГИДРОГЕНАЗЫ

... 1. Соединение формулы ! R1-CO-X-Y-Z-R2, ! в которой ! Х и Z каждый представляет собой необязательные группы, независимо выбранные из насыщенных или ненасыщенных углеродных цепей, имеющих 1-3 атома углерода в длину, ! Y представляет собой SO, S, SO2, CH=CH, CH2CH2 или О, ! R1 выбран из следующих групп ! ! ! где линия обозначает точку присоединения, ! R2 представляет собой гетероарильную группу, включающую 15 необязательно замещенное 5- или 6-членное кольцо, где кольцо содержит только углерод и по крайней мере один азот, или содержит только углерод и по крайней мере два азота и по крайней мере одну серу, ! и где (i) когда R1 представляет собой , и группа -CO-X-Y-Z-представляет собой CO-CH2-SO, СО-СН2-S или CO-CH2-SO2, то R2 является отличным от , и ! (ii) когда R1 представляет собой, , и группа -CO-X-Y-Z- представляет собой -СО-СН2-О-, то R2 является отличным от . ! 2. Соединение по п.1, где R1 представляет собой . ! 3. Соединение по п.1, где R1 представляет собой . ! 4. Соединение по п.1 ...

КОНЪЮГАТЫ RGD-(БАКТЕРИО)ХЛОРОФИЛЛ ДЛЯ ФОТОДИНАМИЧЕСКОЙ ТЕРАПИИ И ВИЗУАЛИЗАЦИИ НЕКРОТИЧЕСКИХ ОПУХОЛЕЙ

... 1. Фармацевтическая композиция, содержащая фармацевтически приемлемый носитель и конъюгат содержащего RGD пептида или пептидомиметика RGD и хлорофилльного или бактериохлорофилльного фотосенсибилизатора, для минимально ивазивной нацеленной на опухоль визуализации, нацеленной на опухоль фотодинамической терапии (PDT) и/или интерактивного прогнозирования некротических опухолей, где указанный фотосенсибилизатор представляет собой хлорофилл или бактериохлорофилл формулы I, II или III: !! где M представляет собой 2H или атом, выбранный из группы, состоящей из Mg, Pd, Pt, Co, Ni, Sn, Cu, Zn, Mn, In, Eu, Fe, Au, Al, Gd, Dy, Er, Yb, Lu, Ga, Y, Rh, Ru, Si, Ge, Cr, Mo, P, Re, Tc и Tl и их изотопы и радиоизотопы; ! X представляет собой O или N-R7; ! каждый из R1, R'2 и R6 независимо представляет собой Y-R8, -NR9R'9 или -N+R9R'9R"9A-; или R1 и R6 в формуле II вместе с атомами углерода, к которым они присоединены, образуют кольцо, содержащее пептид RGD или пептидомиметик RGD; ! Y представляет собой O ...

КОМПОЗИЦИИ, ПОЛЕЗНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ ПОТЕНЦИАЛЗАВИСИМЫХ НАТРИЕВЫХ КАНАЛОВ

... 1. Соединение формулы I ! ! или его фармацевтически приемлемая соль, где ! X представляет собой O, S, NR, C(O) или C(R)2; ! кольцо A представляет собой фенильное или 5-7-членное гетероарильное кольцо, где кольцо A необязательно замещено до y заместителями R5; ! R1 и R2, каждый независимо, представляет собой водород или C1-6алифатическую группу, где до двух атомов углерода, не связанных с атомом азота, необязательно заменены на O, S, NR или C(O); ! x равен 0-4; !y равен 0-4; ! z равен 0-4; ! каждый из R3, R4 и R5 независимо представляет собой Q-Rx; ! Q представляет собой связь или C1-6алифатическую цепь, где до двух, не прилегающих друг к другу, метиленовых звеньев Q необязательно заменена на CO, CO2, COCO, CONR, OCONR, NRNR, NRNRCO, NRCO, NRCO2, NRCONR, SO, SO2, NRSO2, SO2NR, NRSO2NR, O, S или NR; ! каждый Rx независимо выбран из R', галогена, NO2, CN, OR', SR', N(R')2, NR'C(O)R', NR'C(O)N(R')2, NR'CO2R, C(O)R', CO2R', OC(O)R', C(O)N(R')2, OC(O)N(R')2, SOR', SO2R', SO2N(R')2, NR'SO2R', ...

СОЕДИНЕНИЯ /ЛИГАНДЫ/, ОБЛАДАЮЩИЕ ИЗБИРАТЕЛЬНОСТЬЮ В ОТНОШЕНИИ РЕЦЕПТОРОВ РЕТИНОИДА Х, ФАРМАКОМПОЗИЦИИ, СПОСОБЫ МОДУЛИРОВАНИЯ ПРОЦЕССОВ, ОПОСРЕДУЕМЫХ РЕЦЕПТОРАМИ РЕТИНОИДА Х, СПОСОБ ЛЕЧЕНИЯ

Примерами таких соединений являются бициклические бензил, пиридинил, тиофен, фуранил и пиррол производные. Описаны способы применения соединений для модуляции процессов, избирательно опосредованных рецепторами ретиноида X.

ПРОИЗВОДНЫЕ ЛЕПТИНА

... 1. Соединение или его фармацевтическая соль, амид или сложный эфир с общей формулой Z-Y-X-лептиновое соединение, в котором Z представляет собой ацильную группу, содержащую 12-22 атома углерода и содержащую C-концевую карбоновую кислоту или C-концевую тетразольную группу;Y представляет собой спейсер, выбранный из группы, состоящей из связи,игде m составляет 0, 1, 2, 3, 4, 5 или 6; n составляет 1, 2 или 3; s составляет 0, 1, 2 или 3; p составляет 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 или 23; r составляет 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 или 23;X является группой для заякоривания соединения лептина и представляет собойилигде «*» указывает точку группировки, которая ориентирована по направлению к соединению лептина, а «*”» указывает точку группировки, которая ориентирована по направлению к Z.2. Соединение по п.1, где Z-Y-X-группировка связана с аминогруппой, присутствующей в N-концевой альфа-аминогруппе в соединении ...

НИТРООКСИПРОИЗВОДНЫЕ ЛОЗАРТАНА, ВАЛСАРТАНА, КАНДЕСАРТАНА, ТЕЛМИСАРТАНА, ЭПРОСАРТАНА И ОЛМЕСАРТАНА В КАЧЕСТВЕ БЛОКАТОРОВ РЕЦЕПТОРОВ АНГИОТЕНЗИНА II ДЛЯ ЛЕЧЕНИЯ СЕРДЕЧНО-СОСУДИСТЫХ ЗАБОЛЕВАНИЙ

... 1. Соединения общей формулы (I) или их фармацевтически приемлемые соли или стереоизомерыгде s равно 1 или 2;R выбирают из следующих остатков блокаторов рецептора ангиотензина II формулы (II) или (III):гдеRпредставляетили -N, где -Nпредставляет собой способную к связыванию с Y группу, имеющую одно из следующих значений:-СОО-, -О-, -CONH-, -ОСО-, -ОСОО- илигде R' и R" одинаковые или разные и представляют собой Н или прямой или разветвленный C-Cалкил;Rвыбирают из группы, состоящей изгде m целое число, равное 0 или 1, и No как указано выше;где Nимеет значения, указанные для No или равно -СООН;при условии, что по крайней мере одна из групп Nравна -СОО- или -CONH-, то есть это группа, способная связываться с Y;Y представляет собой двухвалентный радикал, имеющий следующие значения:a)прямой или разветвленный C-Cалкилен, преимущественно С-С, необязательно замещенный одним или более заместителями, выбранными из группы, состоящей из: атомов галогена, гидрокси, -ONOили Т, где Тпредставляет -СО(O)(С-Салкил ...

АГОНИСТЫ GPR40

... 1. Соединение формулы (I):где кольцо А представляет собой возможно замещенную фенильную группу;кольцо В представляет собой возможно замещенную фенильную группу;Х представляет собой связь или линкерный фрагмент, содержащий от 1 до 8 атомов в линейной цепи;Y представляет собой связь или линкерный фрагмент, содержащий от 1 до 8 атомов в линейной цепи;Z представляет собой связь или выбран из группы, состоящей из возможно замещенного C-Cарила и возможно замещенного C-Cгетероарила, -С(=O)-, -C(=NR)-, -(CRR)-, -(CRR)O-, -(CRR)S-, -(CRR)NR'-, или представляет собой гетероатомную группу, выбранную из группы, состоящей из S, О, Р и NR'', где R'' выбран из группы, состоящей из Н, возможно замещенного C-Cалкила, возможно замещенного С-Сгетероалкила, возможно замещенного С-Сциклоалкила, возможно замещенного С-Cарила и возможно замещенного C-Cгетероарила;L представляет собой группу, способную высвобождать катион, или ее соль;Rвыбран из группы, состоящей из Н, OR, возможно замещенного C-Cалкила, возможно ...

ПРОИЗВОДНЫЕ N-АЦИЛ-N-ФЕНИЛПИПЕРАЗИНА, ИСПОЛЬЗУЕМЫЕ (КРОМЕ ТОГО) ДЛЯ ПРОФИЛАКТИКИ ИЛИ ЛЕЧЕНИЯ ДИАБЕТА

... 1. Соединение, представленное формулойгде кольцо A представляет собой бензольное кольцо, необязательно дополнительно замещенное;кольцо B представляет собой пиперазиновое кольцо, необязательно дополнительно замещенное; иR представляет собой заместитель,при условии, что трет-бутил 4-[2-трет-бутил-5-({[2-(1H-индазол-6-иламино)пиридин-3-ил]карбонил}амино)фенил]пиперазин-1-карбоксилат,или его соль.2. Соединение или его соль по п.1, где R представляет собой необязательно замещенную углеводородную группу, необязательно замещенную гетероциклическую группу, необязательно замещенную аминогруппу или ацильную группу.3. Соединение или его соль по п.1, где кольцо A представляет собой бензольное кольцо, необязательно замещенное 1-3 заместителями, выбранными из (a) атома галогена и (b) Cалкильной группы.4. Соединение или его соль по п.1, где кольцо A представляет собой бензольное кольцо.5. Соединение или его соль по п.1, где кольцо B представляет собой пиперазиновое кольцо.6. Соединение или его соль по ...

НОВЫЕ ПРОИЗВОДНЫЕ ТЕТРАЗОЛОНА

СОЕДИНЕНИЯ ДЛЯ ЛЕЧЕНИЯ МЕТАБОЛИЧЕСКИХ ЗАБОЛЕВАНИЙ

... 1. Соединение формулы ! ! где m равно 1; n равно 1 или 2; t равно 0 или 1; и A представляет собой фенил, замещенный 2 группами, выбранными из галогена, алкила, содержащего 1 или 2 атома углерода, перфторметила и перфторметокси. ! 2. Соединение формулы ! ! где m равно 1; n равно 1 или 2; t равно 0 или 1; и A представляет собой фенил, замещенный 2 группами, выбранными из: галогена, алкила, содержащего 1 или 2 атома углерода, перфторметила и перфторметокси.

ПРОИЗВОДНЫЕ 1-БЕНЗОИЛПИПЕРАЗИНА В КАЧЕСТВЕ ИНГИБИТОРОВ ПОГЛОЩЕНИЯ ГЛИЦЕРИНА ДЛЯ ЛЕЧЕНИЯ ПСИХОЗОВ

... 1. Соединения формулы где Ar означает замещенный арил или незамещенный или замещенный 6-членный гетероарил за исключением 4-пиридина, содержащий один, два или три атома азота, причем арильная и гетероарильная группы замещены одним или более заместителями, выбранными из группы, включающей гидрокси, галоген, CN, C1-С6алкил, C1-С6алкил, замещенный галогеном, C1-С6алкокси, C1-С6 алкокси, замещенный галогеном, NR7R8, C(O)R9 или SO2R10, R1 означает водород или C1-С6алкил, R2 означает галоген, C1-С6алкил, С2-С6алкенил, где атом водорода заменен на группу CN, C(O)-R9 или C1-С6 алкил, или R2 означает С2-С6алкинил, C1-С6алкил, замещенный галогеном, -(СН2)n-(С3-С7)циклоалкил, -(СН2)n-гетероциклоалкил, -C(O)-R9, -(СН2)n-арил или -(CH2)n-5- или 6-членный гетероарил, содержащий один, два или три гетероатома, выбранных из группы, включающей кислород, серу или азот, причем арил, циклоалкил, гетероциклоалкил и гетероарил незамещены или замещены одним или более заместителями, выбранными из группы, включающей ...

ПРОИЗВОДНЫЕ БЕНЗОЛА, ИМЕЮЩИЕ 2 ИЛИ БОЛЕЕ ЗАМЕСТИТЕЛЕЙ

... 1. Соединение, представленное общей формулой (I), или его фармакологически приемлемая соль или сложный эфир: где R1 представляет собой группу, имеющую формулу -COR9 [где R9 представляет собой C1-C10 алкильную группу, C1-C10 алкоксигруппу, галоген-С1-C10 алкоксигруппу (где указанная галоген-С1-C10 алкоксигруппа представляет собой C1-C10 алкоксигруппу, замещенную 1-7 атомами галогенов), фенил-(C1-C10 алкокси)группу, C1-C10 алкиламиногруппу или ди(C1-C10 алкил)аминогруппу (где указанные алкильные группы могут быть одинаковыми или разными и две из указанных алкильных групп могут, вместе с атомом азота указанной аминогруппы, образовывать 5-7-членную насыщенную гетероциклическую группу, содержащую 1-3 атома, выбранных из группы, состоящей из атома азота, атома кислорода и атома серы); R2 представляет собой атом водорода, галоген-С1-C4 алкильную группу (где указанная галоген-С1-C4 алкильная группа представляет собой C1-C4 алкильную группу, замещенную 1-5 атомами галогенов), гидроксильную группу ...

СОЕДИНЕНИЯ ТЕТРАЗОЛА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ АНТАГОНИСТОВ МЕТАБОТРОПНОГО РЕЦЕПТОРА ГЛУТАМАТА

... 1. Соединение формулыгдеXи Xвыбраны из N и С, так что, когда Xпредставляет собой N, Xпредставляет собой С, а когда Xпредставляет собой С, Xпредставляет собой N;Р выбран из арила и гетероарила;если m равен 1, тогда Rприсоединен к Р через атом углерода на кольце Р в мета-положении кольца Р относительно точки присоединения Р при X, а если m равен 2, тогда Rприсоединен к Р через атомы углерода на кольце Р в положениях 2 и 5 кольца Р;Rвыбран из группы, состоящей из гидрокси, галогено, нитро, Cалкилгалогено, ОСалкилгалогено, Cалкила, ОСалкила, Салкенила, ОСалкенила, Салкинила, ОСалкинила, СалкилСциклоалкила, ОСалкилСциклоалкила, Салкиларила, ОСалкиларила, СНО, (CO)R, O(CO)R, O(CO)OR, C(CNR)OR, СалкилOR, ОСалкилOR, Cалкил(СО)R, ОСалкил(СО)R, СалкилCOR, ОСалкилCOR, Салкилциано, ОСалкилциано, CалкилNRR, OCалкилNRR, Cалкил(CO)NRR, OCалкил(CO)NRR, CалкилNR(CO)R, ОСалкилNR(CO)R, CалкилNR(CO)NRR, СалкилSR, ОСалкилSR, Салкил(SO)R, ОСалкил(SO)R, СалкилSOR, ОСалкилSOR, Салкил(SO)NRR, OCалкил(SO)NRR, CалкилNR ...

ПРОЛОНГИРУЮЩИЕ МЕТКИ ПОЛИПЕПТИДОВ, СОДЕРЖАЩИЕ ТЕТРАЗОЛЬНУЮ ГРУППИРОВКУ

... 1. Способ увеличения периода полужизни молекулы в плазме, включающий ковалентное связывание данной молекулы с биоизостером гетероциклической карбоновой кислоты. 2. Способ увеличения периода полужизни молекулы в плазме, включающий ковалентное связывание данной молекулы с ЧН-тетразолом. 3. Способ увеличения периода полужизни молекулы в плазме, включающий превращение указанной молекулы в соединение общей формулы (I) где G, X и Y независимо представляют собой связь, -S-, -О-, -NH-, -(CH2)1-15- или арилен, возможно замещенный одним или более чем одним алкилом, амино, циклоалкилом, арилом, гетероарилом, галогеном, нитро, низшим алкокси, гидрокси, MeCONH-, алканоилом или циано, либо гетероарилен, возможно замещенный одним или более чем одним алкилом, амино, циклоалкилом, арилом, гетероарилом, галогеном, нитро, низшим алкокси, гидрокси, MeCONH-, алканоилом или циано, и Z представляет собой связь или -(CH2)n-, -O-(CH2)n-, -S-(CH2)n-, -(ОСН2СН2)n-, -(CF2)n-, -O-CH2-(CF2)n-, -S-CH2-(CF2)n-, где n ...

ЗАМЕЩЕННОЕ ПРОИЗВОДНОЕ ФЕНИЛАЗОЛА

... 1. Соединение, представленное общей формулой (I):,где кольцо А представляет собой* обозначает положение связывания с бензольным кольцом,X представляет собой СН или N,Rпредставляет собой -C(=O)-NH-R, -NH-C(=O)-NH-Rили -S(=O)-R,Rпредставляет собой -F или -Н,Rпредставляет собой -СНили -СН,Rпредставляет собой,Rпредставляет собой -H или представляет собой C1-C6 алкильную группу, C3-C6 циклоалкильную группу или,каждая из которых может быть замещена 1-3 группами -OH;или его фармацевтически приемлемая соль.2. Соединение по п. 1, где кольцо А представляет собой,Rпредставляет собой -C(=O)-NH-Rили -NH-C(=O)-NH-R,Rпредставляет собой -F, иRпредставляет собой;или его фармацевтически приемлемая соль.3. Соединение по п. 1, где кольцо А представляет собой,Rпредставляет собой -С(=O)-NH-R,Rпредставляет собой -F,Rпредставляет собой,иRпредставляет собой гидроксиизопропильную группу или циклопропильную группу;или его фармацевтически приемлемая соль.4. Соединение по п. 1, где кольцо А представляет собой,Rпредставляет ...

Способ получения солей 3-карбокситиоксантон-10,10-диоксида

Способ получения производных 3-алкил-4-сульфамоиланилина

Способ получения 7-амино-3-(1-карбоксиметилтетразол-5-илтиометил)3-цефем-4-карбоновой кислоты

Фунгицидный состав

Способ получения карбонилзамещенных 1-сульфонилбензимидазолов

Способ получения производных бензола

Изобретение относится к кислородсодержащим соединениям, в частности к получению производных бензола ф-лы но RI CH3C- Q}-CPZ- )-C|0)-A-R2 где RI - этил или пропил; R2 - СООН или 5-тетразолил; А - Ci-Ce-алкилиден с прямой или разветвленной цепью, которые являются антагонистами лейкотриенов. Цель изобретения - разработка способа получения более активных соединений. Получение ведут из соответствующего производного бен- зола и соответствующего фенола с последующим, при необходимости, гидролизом или взаимодействием с производным азида. 1 табл.

Способ получения простагландинов или их солей

Способ получения гетероциклических производных циклобутиламинометана

Изобретение касается гетероциклических производных, в частности циклобутйламинометана общей формулы I Я2ЯзЯ1 СбН2- с- СН2- СН2- СН2 GH(R01S1H2 где f2-фурил , 5-метилфурил-2; тиенил; 1метилЬиррол-2-ил; 1-метилимидазол-2ил; пиридил; 4-метилтиазол-2-ил; 1метилпиразол-5-ил; 1,3-дитиан-2-ил В бензольном кольце R, .а К зависимо друг от друга Н, С1, С , (СН , ОСИ,,, SCH, и Клвместе взятые с соседними атомами углерода, с которыми они связаны, образуют второе бензольное кольцо, которое может быть незамещенным или замещенным хлором, которые, как обладающие антйдепрессантной активностью, могут-использоваться в медицине. Для выявления физиологической активности в указанном ряду соединений получены новые соединения I. Процесс ведут восстановлением соответствующей группы C(R)NY при X - углеродном атоме, где Y - литий или группа MgBr или i MgCl. Восстановление ведут с помощью СО боргидрида натрия в среде оганического растворителя, например этанола, пропан-2-ола, диэтиленгликольдиметилового эфира при температуре ...

Способ борьбы с нежелательной растительностью

Способ получения производных тетразолилуксусной кислоты или ее эфиров, или их солей

Способ получения 5-[4-(4-ацетил-3-гидрокси-2-пропилбензилокси)бензил]-тетразола

Изобретение касается замещенных гетероциклических веществ, в частности получения 5-[4-(4-ацетил-3-гидрокси-2-пропилбензилокси)-бензил]тетразола, используемого для лечения аллергических заболеваний, например астмы. Цель - создание нового более активного вещества указанного класса. Синтез ведут реакцией азида тетраметилгуанидиния с 4-[4-ацетил-3-гидрокси-2-пропилбензилокси]фенилацетонитрилом в среде диметилформамида в атмосфере аргона при 120-123°С. Выход 55,8%, т.пл. 155-157°С, брутто-ф-ла C20H22N4O3. Новое вещество малотоксично и имеет более высокий срок службы (6 ч, против 0,6 мин в известном случае). 1 табл.

Способ получения производных 1-оксо-5-инданилоксиуксусной кислоты

Способ получения замещенных 1-сульфонилбензимидазолов

MIT CARBONYLAMINO-N-ALKANCARBONSAEURE-GRUPPEN SUBSTITUIERTE VINYLAROMATEN UND IHRE VERWENDUNG

Naphthalen-Derivate und ihre Verwendung als PGE- Agonisten und Antagonisten

Verfahren zur Herstellung 1-substituierte-5(4H)-Tetrazolinone

Substituierte Sulfonamide, Verfahren zu deren Herstellung und die enthaltenden Heilmittel.

3-SUBSTITUIERTE-7-SUBSTITUIERTEALKANAMIDO-3-CEPHEM-4-CARBONSAEURE-VERBINDUNGEN, VERFAHREN ZU IHRER HERSTELLUNG UND SIE ENTHALTENDE PHARMAZEUTISCHE MITTEL

Verfahren zur Herstellung von Aminocarbonsaeureamiden, welche die Atomgruppierung ? enthalten

Naphthalin-Derivate

VERBINDUNGEN MIT SELEKTIVER WIRKUNG FUER RETINOID X REZEPTOREN, UND MITTEL FUER STEUERUNG FUER DURCH RETINOID X REZEPTOREN BEDINGTE PROZESSE

NEUE CEPHALOSPORINDERIVATE, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG

5-Lipoxygenasehemmende 4-(4-Phenyl-1-piperazinyl)phenole.

Aldose-Reductase-Inhibitor.

2-SUBSTITUIERTE-2-CYCLOPENTENONE UND DIESE ALS AKTIVE SUBSTANZEN ENTHALTENDE CARCINOSTATIKA UND OSTEOGENESIS-PROMOTER

SUBSTITUIERTE DI-T-BUTYLPHENOLE.

5-Iodtetrazole

Die Verbindungen der Formel (I), DOLLAR F1 in welcher DOLLAR A R·1· für Wasserstoff oder jeweils gegebenenfalls substituiertes Alkyl, Alkenyl, Alkinyl oder Phenyl steht, DOLLAR A eignen sich hervorragend als Mikrobizide zum Schutz von Pflanzen und Materialien.

Kohlenstoffmaterial

Kohlenstoffmaterial mit organischen Gruppen, erhältlich durch Umsetzung von Kohlenstoffmaterial mit organischen Verbindungen der allgemeinen Formel 1 DOLLAR F1 DOLLAR A Die erfindungsgemäßen Kohlenstoffmaterialien mit organischen Gruppen können als Füllstoffe, Verstärkerfüllstoffe, UV-Stabilisatoren, Leitfähigkeitsruße oder Pigmente verwendet werden.

New heterocyclylalkoxy-substituted benzoyl ketone derivatives are herbicides useful as defoliants, desiccants and especially weedkillers

Heterocyclylalkoxy-substituted benzoyl ketones are new. The heterocyclylalkoxy-substituted benzoyl ketones are compounds of formula (I) and their tautomers and salts: n = 0-2; A = alkanediyl; R<1> = group of formula (a)-(d): m = 0-6; R<5> = halo, or alkyl, alkyl-S- or aryl (each optionally substituted); or two R<5>'s together = alkanediyl; R<6> = OH, OCHO, halo, or alkyl-O-, alkyl-S-, alkyl-SO-, alkyl-SO2-, alkyl-CO-O-, alkyl-O-CO-O-, alkyl-NH-CO-O-, alkyl-SO2-O-, alkenyl-O-, alkynyl-O-, aryl-O-, aryl-S-, aryl-SO-, aryl-SO2-, aryl-CO-O-, aryl-CO-alkyl-O-, aryl-SO2O-, aralkyl-O-, aralkyl-S-, aralkyl-SO- or aralkyl-SO2- (each optionally substituted); R<7> = H; CN; CONH2; CSNH2; halo; or alkyl, alkyl-O-, alkyl-S-, alkyl-SO-, alkyl-SO2-, alkyl-O-CO- or cycloalkyl (each optionally substituted); R<8> = H; or alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl (each optionally substituted); R<9> = OH; OCHO; or alkyl-O-, alkyl-CO-O, alkyl-O-CO-O-, alkyl-NH-CO-O-, alkyl-SO2-O-, ...

LICHTEMPFINDLICHES FARBPHOTOGRAPHISCHES MATERIAL

Pharmaceutical compositions containing pivaloyloxymethyl 7-[2-(2-aminothiazol-4-yl)-2-(syn)methoxyiminoacetamido]deacetoxycepha lo-sporanate and its salts

The invention relates to pharmaceutical compositions containing pivaloyloxymethyl 7-[2-(2-aminothiazol-4-yl)-2-(syn)methoxyiminoacetamido]deacetoxycepha losporanate of the formula in which M is , R3 is hydrogen and R2NH is an optionally protected amino group or its pharmaceutically acceptable salts and a pharmaceutically acceptable ancillary substance or a pharmaceutically acceptable diluent.

VERFAHREN ZUM ENTWICKELN EINES LICHTEMPFINDLICHEN PHOTOGRAPHISCHEN SILBERHALOGENIDMATERIALS

LICHTEMPFINDLICHES FARBPHOTOGRAPHISCHES SILBERHALOGENIDMATERIAL

P-GLYCOPROTEIN-INHIBITOR, VERFAHREN ZU DESSEN HERSIESEN ENTHÄLT

Photographisches Material

CYCLISCHE SCHWEFELVERBINDUNGEN

ANTIDIABETISCHE MITTEL

SULFONAMIDDERIVATE, IHRE HERSTELLUNG UND IHRE THERAPEUTISCHE ANWENDUNG

Therapeutic compounds

Chemical compounds

METHOD OF ACYLATION

... 1472952 Preparing esters and amides FUJISAWA PHARMACEUTICAL CO Ltd 25 April 1974 [13 Aug 1973 4 March 1974] 39596/76 Divided out of 1472951 Heading C2C [Also in Division C3] A method of acylating a compound having a hydroxy, amino or imino group comprises reacting the compound with a compound having a carboxy group in the presence of a catalyst of formula where R 1 is an organic group and R 2 O is the residue of a N-hydroxy compound having a pKa value of not more than 6. Thus R 2 O may be the residue of (a) a nitrogen containing ring N-hydroxy compound, (b) an aliphatic or aromatic hydroxy compound, e.g. a residue of formula where R 3 and R 4 are each nitro, cyano, carbamoyl, or esterified carboxyl, (c) or a residue of formula where R 5 and R 6 are each hydrogen, acyl, aryl or arylazo.

INTERMEDIATES & PROCESSES FOR PREPARATION OF ANTIHYPERCHOLESTEROLEMIC TETRAZOLE COMPOUNDS

Aromatic compounds

PHOTOGRAPHIC DEVELOPMENT PROCESS USING DEVELOPMENT INHIBITOR- RELEASING TYPE COMPOUNDS AND PHOTOGRAPHIC MATERIALS THEREFOR

... 1423588 Photographic chemicals KONISHIROKU PHOTO INDUSTRY CO Ltd 23 Nov 1973 [29 Nov 1972] 54447/73 Heading C2C [Also in Division G2] The following compounds used as photographic development inhibitor releasing compounds are prepared conventionally ...

7-(3-chloro-isoxazole-5-yl)-acetamido-3-(1-methyl-1H-1,2,3,4-tetrazole-5-yl)-thiomethyl-ceph-3-em-4-carboxylic acid

Compound (I> and pharmacologically acceptable salts thereof.f ...

ANTIHYPERCHOLESTEROLEMIC TETRAZOLE COMPOUNDS

LIGHT-SENSITIVE SILVER HALIDE PHOTOGRAPHIC MATERIAL

... 1324046 Light-sensitive silver halide photographic material KONISHIROKU PHOTO INDUSTRY CO Ltd 19 April 1971 [20 March 1970] 24745/71 Heading G2C A photographic element comprising a support carrying a layer of a light sensitive silver halide emulsion, contain in a layer or layers thereof (A) at least one compound of the formula:- wherein R 1 is 1-5C alkyl or sulphoalkyl, hydroxyalkyl, or alkoxycarbonylalkyl the alkyl portions having 1-5C or phenylcarbonylmethyl; R 2 is alkyl or alkenyl each having 1-5C or sulphoalkyl, hydroxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, acyloxyalkyl, phenyl or sulpho- or carboxysubstituted phenyl; Z 1 forms with N-(CH=CH) n -C a 5-or-6-membered ring; Z 2 forms with C-CO-N a 5-membered ring; and n is 0 or 1; and (B) at least one compound of the formula:- wherein R 4 and each of R 5 and R 6 are H, alkyl, alkenyl, aryl or aralkyl. The element may additionally contain a spectrally sensitising dye in at least one silver halide emulsion layer. The compound of the ...

THERAPEUTIC AGENTS

Improvement in or relating to silver salt diffusion transfer photographic materials

Compounds of formula wherein R is hydrogen, halogen or methyl, R1 is alkyl, aryl, aralkyl, aminoalkyl, carboxyalkyl or sulphoalkyl, R2 is alkyl or R1 and R2 complete a heterocyclic ring, are prepared by heating the appropriate 1-phenyl-5-mercaptotetrazole, formalin and the appropriate amine. Compounds of formula wherein R is as above, Y is or piperazino and R1 is as above, are prepared by heating the appropriate 1-phenyl-5-mercaptotetrazole, formalin and the appropriate amine.

Tetrazolyl alkanoic acids

... 1,129,393. Tetrazolylalkanoic acids. MILES LABORATORIES Inc. 6 Dec., 1966 [13 Dec., 1985], No. 54597/66. Heading C2C. Novel tetrazolyl alkanoic acids (and soluble salts thereof ) which are useful as anti-inflammatory agents and have the general formula wherein R 1 is an aryl or heterocyclic aryl radical, e.g. phenyl, halo- or alkoxy-substituted phenyl, furyl, pyridyl or thienyl, R 2 is hydrogen or an aryl or heterocyclic aryl radical, e.g. phenyl, halo- or alkoxy-substituted phenyl, furyl, pyridyl or thienyl, R 3 is hydrogen or an alkyl, aryl or heterocyclic aryl radical, e.g. phenyl, halo- or alkoxy-substituted. phenyl, furyl, pyridyl or thienyl, m is 0, 1 or 2 and n is 0, 1, 2 or 3, are prepared by the base catalysed alkylation of the corresponding 5-substituted tetrazole using as alkylating agent a compound which will substitute the tetrazole at the 2-position with the odesired carbolix acid side chain or a precursor thereof. Alkylating agents include halo esters and halo nitriles, necessitating ...

5-(Dihydroxyphenoxy)tetrazoles as sweeteners

Dihydroxyphenoxy-1H-tetrazoles and their salts are used as non-nutritive sweeteners.

Taspase1 inhibitors and their uses

Provided herein are small molecule inhibitors of Taspase1 and methods of using the small molecule inhibitors of Taspase1 to treat neoplasm in subjects in need thereof.

Compounds and Methods for Treating Cancer and Diseases of the Central Nervous System

Disclosed are compounds of the general formula (I): compositions comprising an effective amount of said compounds either alone or in combination with other chemotherapeutic agents, and methods useful for treating or preventing cancer and for inhibiting tumour tissue growth. These compounds attenuate the oxidative damage associated with increased heme-oxygenase activity and can reduce cell proliferation in transformed cells. In addition, the described compounds and compositions are useful as neuroprotectants and for treating or preventing neurodegenerative disorders and other diseases of the central nervous system.

Diacylethylenediamine compound

[Problem] A compound which is useful as an anti-obesity agent is provided. [Means for Solution] The present inventors have investigated a compound having a DGAT1 inhibitory action, which is promising as an active ingredient of a pharmaceutical composition for treating obesity, type II diabetes mellitus, fatty liver, and diseases associated with these diseases, and as a result, they have found that the diacylethylenediamine compound of the present invention has an excellent DGAT1 inhibitory action, thereby completing the present invention. That is, the diacylethylenediamine compound of the present invention has a DGAT1 inhibitory action, and can be therefore used as an agent for preventing and/or treating obesity, type II diabetes mellitus, fatty liver, and diseases associated with these diseases.

3-substituted propanamine compounds

Racemic or enantiomerically enriched 3-substituted propanamine compounds represented by the following structural formula (I): or a pharmaceutically acceptable salt thereof are disclosed. Pharmaceutical compositions containing the subject compounds are also disclosed. The subject compounds are useful for the treatment of diseases of the central nervous system, such as depression, anxiety and pain disorders.

Pharmaceutical product

An agent for suppressing the production of various cytokines (IL-8 and the like) and inflammatory mediators, an agent for suppressing the expression of COX-II and the like, or an inhibitor of various phosphorylation enzymes (ATF2 and the like), which contains a TLR signaling inhibitory substance, preferably a compound represented by the formula (I) or the formula (II) wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof.

Compound inhibiting in vivo phosphorus transport and medicine containing the same

An objective of the present invention is to provide compounds that can effectively suppress the concentration of phosphorus in serum to effectively prevent or treat diseases induced by an increase in concentration of phosphate in serum. The compounds according to the present invention are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof: wherein A represents an optionally substituted five- to nine-membered unsaturated carbocyclic moiety or a five- to nine-membered unsaturated heterocyclic moiety, and represents a single bond or a double bond, R 5 represents optionally substituted aryl or the like, Z represents —N═CHR 6 R 7 or the like, R 6 and R 7 represent H, optionally substituted alkyl, optionally substituted aryl or the like, R 101 and R 102 together form ═O, and R 103 and R 104 represent H, or R 101 and R 104 together from a bond, and R 102 and R 103 together form a bond.

Substituted carbamoylcycloalkyl acetic acid derivatives as nep

The present invention provides a compound of formula I; or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , B, X, m and n are defined herein. The invention also relates to a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides pharmaceutical composition of compounds of the invention, and a combination of pharmacologically active agents and a compound of the invention.

Compounds, Compositions and Methods for Modulating Uric Acid Levels

Described herein are compounds useful in the reduction of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

Dual-acting antihypertensive agents

The invention is directed to compounds of formula I: wherein Ar, r, R 3 , X, and R 5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula I have AT 1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and a process and intermediates for preparing such compounds.

Substituted Esters as Cannabinoid-1 Receptor Modulators

Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, Alzheimer's disease, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, cirrhosis of the liver, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the promotion of wakefulness.

Process and intermediate compounds useful in the preparation of statins

There is provides a process for the preparation of a compound of formula (7): wherein R is an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; provides that R is not a compound of Formula (a): wherein R a represents an alkyl group, such as a C 1-16 alkyl group, and preferably an isopropyl group; R b represents an aryl group, preferably a 4-fluorophenyl group; R c represents hydrogen, a protecting group or an alkyl group, such as a C 1-16 alkyl group, and preferably a methyl group; and Rd represents hydrogen, a protecting group or a SO 2 R e group where R e is an alkyl group, such as a C 1-16 alkyl group, and preferably a methyl group.

Propynoic Acid Carbamoyl Methyl-Amides and Pharmaceutical Compositions and Methods Based Thereon

This invention discloses a series of novel propynoic acid carbamoyl methyl-amides (PACMAs), methods for synthesizing the PACMAs and pharmaceutical compositions containing the PACMAs. These novel compounds and compositions show cytotoxicity in cancer cells and are useful as lead compounds for anti-cancer drugs or pharmaceutical agents. This invention also discloses treatment methods that uses the PACMAs and pharmaceutical compositions as well as methods for promoting the release and nuclear localization of the transcription factor Nrf2. 4. A compound according to claim 1 , wherein said compound further contains a substituent capable of being used in a biological or medical diagnostic imagining technique to quantify or identify associated biomarker proteins.5. A compound according to claim 3 , wherein said compound further contains a substituent capable of being used in a biological or medical diagnostic imagining technique to quantify or identify associated biomarker proteins.7. A pharmaceutical composition comprising any of the compounds of to and a pharmaceutically acceptable carrier.8. A method for treatment a cancer subject claim 3 , comprising the step of:{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, 'administering to a person in need of said treatment method an effective amount of the pharmaceutical composition according to .'}9. A method of claim 8 , where the cancer is: breast cancer claim 8 , ovarian cancer claim 8 , prostate cancer claim 8 , colon cancer claim 8 , brain cancer claim 8 , pancreatic cancer claim 8 , skin cancer claim 8 , lung cancer claim 8 , and multiple myeloma.10. A method for promoting the release and nuclear localization of the transcription factor Nrf2 comprising the step of:{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, 'administering an effective amount of the pharmaceutical compositions according to .'}10. A biological or medical diagnostic imaging technique claim 8 , comprising:{'claim-ref': [{'@idref': 'CLM-00004', 'claims 4 ...

SUBSTITUTED AMINOPROPIONIC DERIVATIVES AS NEPRILYSIN INHIBITORS

The present invention provides a compound of formula I′; 3. The compound of wherein:{'sup': '1', 'sub': '1-7', 'Ris H or Calkyl;'}{'sup': 2', 'a', 'b', 'a', 'b, 'sub': 1-7', '3-7', '1-7', '1-7', '6-20', '1-7, 'Rfor each occurrence, is independently Calkyl, halo, Ccycloalkyl, hydroxy, Calkoxy, haloCalkyl, —NRR, Caryl, heteroaryl or heterocyclyl; wherein Rand Rfor each occurrence are independently H or Calkyl;'}{'sup': 3', '1', '1, 'Ris A-C(O)X;'}{'sup': '5', 'Ris H; and'}{'sup': 1', 'a', 'b, 'sub': '1-7', 'X and Xare independently OH, —O—Calkyl or NRR;'}{'sup': '1', 'Bis —C(O)NH— or —NHC(O)—;'}{'sup': '1', 'sub': 1-7', '3-7', '1-7', '3-7, 'Ais a linear or branched Calkylene; which is optionally substituted with one or more substituents independently selected from the group consisting of halo, Ccycloalkyl, Calkoxy, hydroxy and O-acetate; in which two geminal alkyl can optionally combine to form a Ccycloalkyl; or'}and wherein each heteroaryl is a monocyclic or bicyclic aromatic ring comprising 5-10 ring atoms selected from carbon atoms and 1 to 5 heteroatoms, and', 'each heterocyclyl is a monocyclic saturated or partially saturated but non-aromatic moiety comprising 4-7 ring atoms selected from carbon atoms and 1-5 heteroatoms, wherein each heteroatom of a heteroaryl or a heterocyclyl is independently selected from O, N and S, or a pharmaceutically acceptable salt thereof., 'n is 0, 1, 2, 3, 4 or 5;'}6. The compound of wherein Ais an optionally substituted linear or branched Calkylene claim 1 , or a pharmaceutically acceptable salt thereof.7. The compounds of wherein Ais CHCH claim 1 , or a pharmaceutically acceptable salt thereof.810-. (canceled)11. The compound of wherein Ris H claim 1 , Ris independently halo claim 1 , Calkoxy claim 1 , hydroxy claim 1 , Calkyl or halo-Calkyl claim 1 , n is 0 claim 1 , 1 or 2 and X and Xare independently OH or —O—Calkyl claim 1 , or a pharmaceutically acceptable salt thereof.12. The compounds of wherein n is 1 or 2; Ris meta-chloro ...

C7-Fluoro Substituted Tetracycline Compounds

The present invention is directed to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

SPIRO COMPOUNDS AND PHARMACEUTICAL USE THEREOF

The spiro compound represented by the following general formula [Ia], its pharmaceutically acceptable salt or a solvate thereof 3. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 , wherein the number of the double bond in ring A of the spiro-ring AB is 0 or 1.4. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 , wherein the number of the double bond in ring B of the spiro-ring AB is 0 or 1.5. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 , wherein n3 is 1 or 2.6. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed claim 1 , wherein the spiro-ring AB may be substituted by 1 to 3 same or different substituent(s).7. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 ,{'sup': '1', 'wherein Ris'}(1) a hydrogen atom,{'sub': 1', '6, '(2) a C-Calkyl group,'}{'sub': 2', '6, '(3) a C-Calkenyl group,'}{'sub': 2', '6, '(4) a C-Calkynyl group,'}{'sub': 1', '6, '(5) a C-Calkoxy group,'}{'sub': 1', '6', '1', '6, '(6) a C-Calkoxy(C-C)alkyl group,'}{'sup': 11', '12', '11', '12, 'sub': 1', '6, '(7) —CONRRin which Rand Rare the same or different and each represents a hydrogen atom or a C-Calkyl group, or'}{'sub': 1', '6, '(8) a five-membered heteroaryl group which has at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and which may be substituted by a C-Calkyl group.'}8. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 ,{'sup': '1', 'wherein Ris'}(1) a hydrogen atom,{'sub': 2', '6, '(2) a C-Calkenyl group,'}{'sub': 2', '6, '(3) a C-Calkynyl group,'}{'sub': 1', '6, '(4) a C-Calkoxy group or'}{'sub': 1', '6, '(5) a five- ...

HIGHLY CRYSTALLINE VALSARTAN

The present invention describes a highly crystalline form of valsartan, pharmaceutical compositions thereof and process for the preparation thereof. 1. A highly crystalline form of valsartan characterized by an XRPD pattern with a peak at about 31.0±0.2 degrees 2-theta and substantially lacking X-ray diffraction peaks between 0 and 8±0.2 degrees 2-theta.2. A highly crystalline form of valsartan having a peak melting point temperature of 140.8° C.±3° C.4. A process for the preparation of a highly crystalline form of valsartan comprising:(a) combining solid valsartan with a solvent that is an ester,(b) heating said combination to a temperature below complete dissolution of the solid valsartan;(c) stirring said mixture for a time effective to form a suspension with the solvents therein that form a mother liquor;(d) separating the solids in the suspension from the mother liquor; and(e) drying said solids to give a highly crystalline form of valsartan.5. A pharmaceutical composition comprising a pharmaceutically effective amount of the highly crystalline form of valsartan of in combination with a pharmaceutically acceptable carrier.6. A method for treating hypertension or elevated blood pressure in a patient comprising administering a pharmaceutical composition comprising a pharmaceutically effective amount of the highly crystalline form of valsartan of in combination with a pharmaceutically acceptable carrier to a patient in need thereof. Polymorphs of valsartan and/or salts thereof are described in China patent publication 200410067406.8, WO2004/083192; WO2007/017897; US Patent Publication 2008/0261959; WO2003/089417 A1; WO2006/076561 A1; WO2003/066606; WO2002/06253, U.S. Pat. No. 6,869,970. However, there remains a need to provide a form of valsartan that has a greater degree of crystallinity compared to known forms or polymorphs of valsartan.The present invention relates to a novel, highly crystalline form of valsartan, pharmaceutical compositions thereof and process ...

PROCESS FOR THE PREPARATION OF VALSARTAN

The present invention relates to a process for the preparation of pure Valsartan (I) substantially free from impurities of formulae (Ia), (Ib), and (Ic), which comprises: (i) condensing 2-(4′-bromomethylphenyl)benzonitrile of formula (II) with L-valine methyl ester hydrochloride of formula (V) in the presence of a base in a solvent to produce N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester of formula (VI); (ii) treating the compound VI of step (i) with acid followed by treating with base to produce pure compound VI substantially free from dimeric impurity of formula (Via); (iii) reacting the pure compound of formula (VI) with n-valeryl chloride in the presence of a base to produce pure N-valeryl-N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VII) substantially free from alkene impurity of formula (Vila); (iv) reacting the compound of formula (VII) with trialkyltin chloride and a metal azide in a solvent at a reflux temperature to produce N-(1-oxopentyl)-N-[[2′-(2-tributyltinte-trazol-5-yl)-(1,1′-biphenyl)-4-yl]methyl]-(L)-valine methyl ester of formula (VHIb) free from thermal degradation impurity (Villa); (v) hydrolyzing the compound of formula (VHIb) in the presence of alkaline conditions to produce Valsartan (I). 2. The process according to claim 1 , wherein the above process is carried out without isolating the intermediate compounds N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VI) claim 1 , N-valeryl-N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VII) and N-(1-oxopentyl)-N-[[2′-(2-tributyltintetrazol-5-yl)-(1 claim 1 ,1′-biphenyl)-4-yl]methyl]-(L)-valine methyl ester (VIIIb).3. The process according to claim 1 , wherein the base used in step-(i) is selected from sodium carbonate claim 1 , sodium bicarbonate claim 1 , potassium carbonate claim 1 , and the solvent is selected from ethers claim 1 , esters claim 1 , chlorinated solvents or mixtures thereof.4. The process according to claim 1 , wherein the acid used in ...

INTERMEDIATES FOR THE PREPARATION OF HMG COA REDUCTASE INHIBITORS AND PROCESSES FOR THE PREPARATION THEREOF

A compound of Formula (1), is disclosed 13. The process as claimed in step (a) of claim 12 , wherein the suitable organic solvent comprises one or more of toluene claim 12 , xylene claim 12 , ethylbenzene claim 12 , cyclohexane claim 12 , hexane claim 12 , heptane claim 12 , methylene dichloride claim 12 , ethylene dichloride claim 12 , and ethyl acetate.14. The process as claimed in step (a) of claim 12 , wherein the base comprises one or more inorganic bases selected from the group consisting of sodium hydroxide claim 12 , potassium hydroxide claim 12 , sodium bicarbonate claim 12 , potassium bicarbonate claim 12 , and sodium hydride claim 12 , or one or more organic bases selected from the group consisting of triethylamine claim 12 , diisopropylethylamine claim 12 , diisopropyl amine claim 12 , 1 claim 12 ,8-diazabicycloundec-7-ene (DBU) claim 12 , and pyridine.15. The process as claimed in step (c) of claim 12 , wherein the dialkylalkoxyborane is selected from group consisting of diethylmethoxyborane claim 12 , diethylethoxyborane claim 12 , and dimethylethoxyborane.16. The process as claimed in step (c) of claim 12 , wherein the base comprises one or more of alkali metal hydrides selected from the group consisting of sodium hydride claim 12 , potassium hydride claim 12 , lithium hydride claim 12 , sodium borohydride claim 12 , potassium borohydride claim 12 , and lithium aluminium hydride.17. The process as claimed in step (c) of claim 12 , further comprising purifying the compound of Formula (5′) in a suitable organic solvent selected from the group consisting of one or more of C-Calcohol claim 12 , water claim 12 , and aliphatic hydrocarbons.18. The process as claimed in step (d) of claim 12 , wherein the suitable reagent comprises one or more of 2 claim 12 ,2-dimethoxypropane claim 12 , 2 claim 12 ,2-dimethoxypentane claim 12 , 1 claim 12 ,1-dimethoxycyclohexane claim 12 , and 2 claim 12 ,2-dimethoxybutane.19. The process as claimed in step (d) of claim 12 , ...

Novel Tetrahydronaphalene Antagonists to the Thromboxane A2 (TP) Receptor

The present invention relates to TP receptor antagonists, which have the ability to bind to TP receptor and optionally cross the blood brain barrier. The invention also provides compositions and methods for treating a disorder wherein activation of TP receptor is detrimental. 1. A composition comprising a TP receptor antagonist , wherein said antagonist comprises the chemical structures set forth in , a salt thereof , a prodrug thereof , and combinations thereof.2. The composition of claim 1 , wherein said antagonist binds to a TP receptor or a TP-like receptor.3. The composition of claim 1 , wherein said antagonist inhibits activation of a TP receptor or a TP-like receptor.4. The composition of claim 1 , wherein said antagonist is able to cross the blood brain barrier of a mammal.5. The composition of claim 1 , wherein said antagonist is not able to cross the blood brain barrier of a mammal.6. The composition of claim 1 , wherein said antagonist is selected from the group consisting of CNDR-51418 claim 1 , CNDR-51281 claim 1 , CNDR-51354 and CNDR-51414.7. A method of treating a disorder associated with activation of a TP receptor in a mammal in need thereof claim 1 , said method comprising administering to said mammal a therapeutically effective amount of a compound claim 1 , wherein said compound comprises a TP receptor antagonist claim 1 , wherein said antagonist comprises the chemical structures set forth in claim 1 , a salt thereof claim 1 , a prodrug thereof claim 1 , and combinations thereof.8. The method of claim 7 , wherein said antagonist is able to cross the blood brain barrier of said mammal.9. The method of claim 7 , wherein said antagonist is not able to cross the blood brain barrier of said mammal.10. The method of claim 7 , wherein said mammal is a human.11. The method of claim 7 , wherein said disorder associated with activation of a TP receptor is a neurodegenerative disorder.12. The method of claim 11 , wherein said neurodegenerative disorder is ...

Hydrothiolation of Unactivated Alkenes

The present invention is a method for promoting hydrothiolation of an unactivated alkenes with a thiol using gallium triflate.

CYTOKINE INHIBITORS

The present invention provides compounds represented by general formula (I): 2. The compound of formula (I) according to claim 1 , wherein{'sub': '1', 'Ris selected from hydrogen or alkyl;'}{'sub': '2', 'Rat each occurrence is independently selected from hydrogen, halogen, hydroxy, alkyl or alkoxy; and'}T is phenyl; which is unsubstituted or substituted by at least one group selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, carboxy, amino, nitro or cyano;or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.6. The compound of formula (I) according to claim 1 , wherein{'sub': '1', 'Ris selected from hydrogen or alkyl;'}{'sub': '2', 'Rat each occurrence is independently selected from hydrogen, halogen, hydroxy, alkyl or alkoxy; and'}T is 5 or 6 membered heteroaryl; wherein the heteroaryl is unsubstituted or substituted by at least one group selected from; halogen, hydroxy, alkyl, haloalkyl, alkoxy, carboxy, amino, nitro or cyano;or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.14. The compound of formula (I) according to claim 1 , wherein the compound is:(+/−)3-(2-Chlorophenyl)-1-(2-hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)prop-2-en-1-one hydrochloride,(−)3-(2-Chlorophenyl)-1-(2-hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)prop-2-en-1-one,(+)3-(2-Chlorophenyl)-1-(2-hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)prop-2-en-1-one,(+/−)3-(3-Bromophenyl)-1-(2-hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)prop-2-en-1-one,(+/−)3-(2,4-Dimethoxy-phenyl)-1-(2-hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)prop-2-en-1-one,(+/−)1-(2-Hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxyphenyl)-3-m-tolylprop-2-en-1-one,(+/−)1-(2-Hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)-3-o-tolylprop-2-en-1-one,(+/−)1-(2-Hydroxy-3-(2-(hydroxymethyl ...

TETRAZOLIUM COMPOUND FOR DETECTING MICROORGANISMS, REAGENT FOR DETECTING MICROORGANISMS AND METHOD FOR DETECTING MICROORGANISMS

The object of the present invention is to provide a compound used in a reagent for detecting microorganisms, by which microorganisms can be rapidly and reliably detected without requiring any special instrument, the reagent for detecting microorganisms, and a method for detecting microorganisms. The object can be achieved by a tetrazolium compound represented by general formula (I) below:

Inhibitors of the Renal Outer Medullary Potassium Channel

This invention relates to compounds having structural Formula (I); and pharmaceutically acceptable salts thereof which are inhibitors of the Renal Outer Medullary Potassium (ROMK) channel (Kir 1.1). The compounds of Formula I are useful as diuretics and natriuretics and therefore are useful for the therapy and prophylaxis of disorders resulting from excessive salt and water retention, including cardiovascular diseases such as hypertension and chronic and acute heart failure. 3. The compound of wherein Ris —H claim 1 , methyl claim 1 , methoxy claim 1 , hydroxy claim 1 , or fluoro claim 1 , or is joined to Rby 2-3 carbon atoms or 1-2 carbon atoms and one heteroatom to form a ring claim 1 , or a pharmaceutically acceptable salt thereof.4. The compound of wherein Ris —H or methyl claim 1 , or is joined to Rby 1-2 carbon atoms or 0-1 carbon atoms and one heteroatom to form a ring claim 1 , or a pharmaceutically acceptable salt thereof.5. The compound of wherein Ris —H or methyl claim 1 , or is joined to Rby 2-3 carbon atoms or 1-2 carbon atoms and and one heteroatom to form a ring claim 1 , or a pharmaceutically acceptable salt thereof.6. The compound of wherein Ris —H claim 1 , or a pharmaceutically acceptable salt thereof.7. The compound of wherein Ris —H claim 1 , or a pharmaceutically acceptable salt thereof.8. The compound of wherein Ris —H claim 1 , or a pharmaceutically acceptable salt thereof.9. The compound of wherein Ris —H claim 1 , or a pharmaceutically acceptable salt thereof.10. The compound of wherein Ris —H claim 1 , or a pharmaceutically acceptable salt thereof.11. The compound of wherein Ris —H claim 1 , or a pharmaceutically acceptable salt thereof.12. The compound of wherein Ris —H claim 1 , halogen claim 1 , methoxy claim 1 , —SCH claim 1 , —COOCHor —CH claim 1 , or is joined to Rby 2-3 carbon atoms or 1-2 carbon atoms and one heteroatom to form a ring claim 1 , or is joined to Rby 1-2 carbon atoms or 0-1 carbon atoms and one heteroatom claim 1 , or ...

METHOD AND DEVICE FOR THE DETECTION OF SULPHUR CONTAINING SPECIES

A method is provided for detecting sulphur-containing species (such as thiophosphorous esters, in particular phosphorylating agents), in which a suspected sulphur-containing species is brought into contact with a tetrazolium compound in the presence of base, typically at a pH of at least 8. A device, kit and tetrazolium compounds for use in such a method are also disclosed. 1. A method for the detection of sulphur containing species , the method comprising:bringing together a tetrazolium reagent, a suspected sulphur-containing species and one of:a base in aqueous alkaline conditions or a nucleophilic base in non-aqueous conditions.2. The method according to claim 1 , wherein the tetrazolium reagent claim 1 , the suspected sulphur-containing species claim 1 , and base are brought together in aqueous alkaline conditions claim 1 , wherein the pH is at least 10.3. The method according to claim 2 , wherein the pH is at least 12.4. (canceled)5. The method according to claim 1 , wherein the tetrazolium reagent is substantially stable to exposure to UV and visible light and substantially stable in the presence of base and substantially stable in the presence of base whilst exposed to UV or visible light.6. The method according to claim 1 , wherein the suspected sulphur-containing species is a species comprising a sulphur moiety bonded with a single bond to an adjacent moiety.7. (canceled)8. The method according to which comprises a method for detecting sulphur-containing phosphorylating agents claim 1 , the method comprising bringing together a tetrazolium reagent claim 1 , a species suspected of being a sulphur-containing phosphorylating agent and one of:a base in aqueous alkaline conditions or a nucleophilic base in non-aqueous conditions.9. method according to comprising sensing for the presence of colouration.10. (canceled)11. (canceled)12. The method according to comprising bringing together the suspected sulphur-containing species claim 1 , the base and tetrazolium ...

USE OF AZIDES IN SYNTHESIS

Described herein are inventive methods for synthesis of tetrazoles. In some embodiments, the method involves the use of a flow reactor. The methods provided herein are capable at being carried out in short reaction times, with high yields, with minimal side reactions, and/or with minimal chance of explosions caused by the presence of azides. 4. The method of claim 1 , wherein the reacting is carried out in the presence of a catalyst.5. The method of claim 4 , wherein the catalyst is ZrBr.6. The method of claim 4 , wherein the catalyst is provided in an amount of about 0.5 equiv claim 4 , about 0.75 equiv claim 4 , about 1 equiv claim 4 , about 1.5 equiv claim 4 , about 2 equiv claim 4 , about 3 equiv claim 4 , about 4 equiv claim 4 , or about 5 equiv. of the compound of formula (I).7. The method of claim 1 , wherein the reacting is carried out in a flow reactor.8. The method of claim 1 , wherein the azide source is NaN.9. The method of claim 1 , wherein the ratio of the azide source to a compound about formula (I) is about 1:1 claim 1 , about 1.05:1 claim 1 , about 1.1:1 claim 1 , about 1.2:1 claim 1 , about 1.3:1 claim 1 , about 1.4:1 claim 1 , about 1.5:1 claim 1 , about 2:1 claim 1 , about 3:1 claim 1 , or about 4:1.10. The method of claim 1 , wherein the conditions comprise reacting at a temperature of about 150° C. claim 1 , about 160° C. claim 1 , about 170° C. claim 1 , about 180° C. claim 1 , about 190° C. claim 1 , about 200° C. claim 1 , about 210° C. claim 1 , about 220° C. claim 1 , or about 230° C.11. The method of claim 1 , wherein the conditions comprise reacting at a temperature between about 150° C. and about 220° C.12. The method of claim 1 , wherein the conditions comprise reacting in a solution comprising water and a polar aprotic solvent.13. The method of claim 12 , wherein the ratio of water to polar aprotic solvent is between about 1:9 and about 9:1.14. The method of claim 1 , wherein the reaction is carried out under conditions suitable for ...

Ethynylbenzene derivatives

Disclosed are compounds of formulae (I), (II), and (II)I: and pharmaceutically acceptable salts thereof, wherein the variables, R, R 1 , R 2 , R 3 , R 101 , L, D, Q, Y, X, and Z are defined herein. These compounds are useful for treating Gram-negative bacteria infections.

TERPENOID ANALOGUES AND USES THEREOF FOR TREATING NEUROLOGICAL CONDITIONS

The present application provides a terpene analogue of Formula (I) or a pharmaceutically acceptable isomer, salt or ester thereof, and methods and uses thereof for treating neurological conditions such as pain in general and neuropathic pain. These terpene analogues can also be used to treat other electrical disorders in the central and peripheral nervous system. Also provided are methods of synthesizing the terpene analogues of Formula I. 2. The method of claim 1 , wherein Y is CH claim 1 , W is CH claim 1 , and X is O—CH claim 1 , O—CH-aryl claim 1 , NH claim 1 , N(H)—CH claim 1 , N—(CH) claim 1 , N(H)—C(═O)-aryl claim 1 , N(H)—C(═O)—CH claim 1 , N(H)—C(═O)-aryl(OH) claim 1 , SOMe claim 1 , or SOMe.3. The method of claim 1 , wherein Y is C═O and X is H claim 1 , OH claim 1 , NHN(H)—CH claim 1 , N—(CH) claim 1 , N(H)-aryl claim 1 , N(Me)OMe claim 1 , N(Me)OH claim 1 , or CF.5. The method of claim 1 , wherein:Y is absent;{'sub': 3', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'X is —C(═O)H, —C(═O)CF—COOH, —CH(OH)CF, —C(OH)(CF), —C(═O)N(Me)OMe, C(═O)N(Me)OH, —CONHAryl, —CONH, —CONHAlkyl, —CON(Alkyl)—SOAryl, —SOalkyl, SOalkyl, —SONHAryl, —SON(Aryl), —SON(Alkyl), —SONHalkyl, or SONH; and'}{'sub': 1', '20, 'W is H, a substituted or unsubstituted Cto Calkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted alkylaryl.'}6. The method of claim 1 , wherein the terpene analogue is selected from the group consisting of:(E)-1-methoxy-3,7-dimethylocta-2,6-diene,(E)-((3,7-dimethylocta-2,6-dienyloxy)methyl)benzene,3,7-dimethyloct-2,6-dienoic acid,N,3,7-trimethylocta-2,6-dienamide,(E)-3,7-dimethylocta-2,6-dien-1-amine,(E)-N-(3,7-dimethylocta-2,6-dienyl)benzamide,(E)-3,7-dimethylocta-2,6-dienal,(E)-3,7-dimethylocta-2,6-dienoic acid,(E)-N-(3,7-dimethylocta-2,6-dienyl)acetamide,(E)-3,7-dimethyl-N-phenylocta-2,6-dienamide,(E)-N-(3,7-dimethylocta-2,6-dienyl)-2-hydroxybenzamide,(E)-N,N,3,7-tetramethylocta-2,6-dienamide,(E)-N,N,3,7- ...

(2-UREIDOACETAMIDO)ALKYL DERIVATIVES AS FORMYL PEPTIDE RECEPTOR 2 MODULATORS

The present invention relates to (2-ureidoacetamido)alkyl derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor 2. 2. A compound according to claim 1 , wherein:{'sup': 3', '11', '16, 'sub': 1-8', '3', '2, 'Ris substituted or unsubstituted Calkyl, halogen, —SR, —CFor —S(O)R.'}4. A compound according to claim 1 , wherein:{'sup': 6', '19, 'sub': 1-8', '2, 'Ris substituted or unsubstituted Calkyl, or —CHR.'}5. A compound according to claim 1 , wherein:{'sup': '26', 'Ris hydrogen;'}{'sup': '27', 'Ris hydrogen;'}{'sup': '28', 'Ris hydrogen; and'}{'sup': '29', 'Ris hydrogen;'}8. A compound according to claim 1 , selected from:Diethyl({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-4-methylpentanoyl]amino}methyl)phosphonate;(2S)-2-({[(4-Bromophenyl)amino]carbonyl}amino)-4-methyl-N-(1H-tetrazol-5-ylmethyl)pentanamide;(2S)-2-({[(4-Bromophenyl)amino]carbonyl}amino)-4-methyl-N-[2-(1H-tetrazol-5-yl)ethyl]pentanamide;(2S)-2-({[(4-Bromophenyl)amino]carbonyl}amino)-N-[(3-hydroxyisoxazol-5-yl)methyl]-4-methylpentanamide;Diethyl({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-4-methylpentanoyl]amino}methyl)phosphonate;Diethyl({[(2S,3S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-methylpentanoyl]amino}methyl)phosphonate;Diethyl({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)pentanoyl]amino}methyl)phosphonate;Diethyl({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-phenylpropanoyl]amino}methyl)phosphonate;Diethyl(2-{[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-4-methylpentanoyl]amino}ethyl)phosphonate;Ethyl hydrogen ({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-4-methyl pentanoyl]amino}methyl)phosphonate;Ethyl hydrogen ({[(2S,3S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-methyl pentanoyl]amino}methyl)phosphonate;Ethyl hydrogen ({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)pentanoyl]amino}methyl)phosphonate;({[(2S)-4-Methyl-2-({[4-(trifluoromethyl)phenyl] ...

Compounds for the treatment of metabolic disorders

Compounds useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis, are disclosed.

HETEROARYLTHIO DERIVATIVES AND ANALOGUES

Heteroarylthio compounds covalently linked to an arylpiperazine moiety for the treatment of neurological conditions. 7. The heteroarylthio compound of claim 1 , wherein m is selected from the group consisting of 2 claim 1 , 3 claim 1 , and 4.8. The heteroarylthio compound of claim 1 , wherein L is substituted with alkyl groups.14. The heteroarylthio compound of claim 1 , wherein the compound is selected from the group consisting of:1-{2-[(1-methyl-1H-imidazol-2-yl)thio]ethyl}-4-[3-(trifluoromethyl)phenyl]piperazine;1-[2-(5-pyridin-4-yl-[1,3,4]oxadiazol-2-ylsulfanyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine;1-{3-[(1-methyl-1H-imidazol-2-yl)thio]propyl}-4-[3-chlorophenyl]piperazine;1-[3-(1-phenyl-1H-tetrazol-5-ylsulfanyl)propyl]-4-(3-chlorophenyl)piperazine; and1-[2-(5-pyridin-4-yl-[1,3,4]oxadiazol-2-ylsulfanyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine.1518-. (canceled)19. The heteroarylthio compound of claim 1 , wherein the compound is selected from the group consisting of:4-{4-[3-(1-methyl-1H-imidazol-2-ylsulfanyl)propyl]piperazin-1-yl}furo[3,2-c]pyridine;4-{4-[3-(1-phenyl-1H-tetrazol-5-ylsulfanyl)propyl]piperazin-1-yl}furo[3,2-c]pyridine; and4-{4-[3-(5-pyridin-4-yl-[1,3,4]oxadiazol-2-sulfanyl)propyl]piperazin-1-yl}furo[3,2-c]pyridine.2021-. (canceled)22. A pharmaceutical composition comprising the heteroarylthio compound of and one or more pharmaceutically acceptable excipients.23. A method of treating a neurological condition claim 1 , comprising the step of administering the heteroarylthio compound of to a subject in need thereof.24. (canceled) This patent application claims the benefit of priority from U.S. Patent Application No. 61/393,349, filed on Oct. 14, 2010 and entitled HETEROARYLTHIO DERIVATIVES AND ANALOGUES. The disclosure of this application is hereby incorporated by reference herein in its entirety.The serotonin receptors, also known as 5-hydroxytryptamine receptors or 5-HT receptors, are a group of G protein-coupled receptors (GPCRs) and ...

N-SUBSTITUTED BENZAMIDES AND METHODS OF USE THEREOF

The invention provides novel compounds having the general formula: 3. The compound of wherein B is N and Ris absent.4. The compound of wherein B is C.5. The compound of wherein R claim 1 , Rand Rare each independently selected from H claim 1 , F claim 1 , or Cl.6. The compound of wherein Ris H claim 1 , F or Cl; Rand Rare each H; and Ris an optionally substituted group selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —CN claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Ccycloalkyl claim 1 , and Calkoxy.7. The compound of wherein Ris Calkyl claim 1 , Chaloalkyl claim 1 , Ccycloalkyl or —NRR.8. The compound of claim 7 , wherein Ris selected from the group consisting of methyl claim 7 , ethyl claim 7 , propyl claim 7 , trifluoromethyl claim 7 , difluoromethyl claim 7 , monofluoromethyl claim 7 , isopropyl and cyclopropyl.11. The compound of wherein Ris selected from the group consisting of: methyl claim 1 , ethyl claim 1 , tert-butyl claim 1 , dimethylamino claim 1 , methylamino claim 1 , amino claim 1 , morpholino claim 1 , azetidino claim 1 , imidazolyl claim 1 , 3-hydroxyazetidino claim 1 , 3-fluoroazetidino claim 1 , cyclopropyl claim 1 , pyrrolidinyl claim 1 , 3 claim 1 ,3-difluoroazetidino claim 1 , tert-butyl claim 1 , ethyl claim 1 , 2-methoxyethyl claim 1 , 3-methoxyazetidino claim 1 , 2-hydroxyethyl claim 1 , 3-hydroxypyrrolidinyl claim 1 , and N-methylimidazolyl.12. The compound of wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is an optionally substituted group selected from the group consisting of Calkylene claim 1 , Calkenylene or Calkynylene.13. The compound of claim 1 , wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)(CH)—CH— or —CHCHCHCH—.14. The compound of claim 13 , ...

Indanyloxyphenylcyclopropanecarboxylic acids

The present invention relates to compounds of general formula I, wherein the groups R 1 , R 2 , R 3 , m and n are defined as in claim 1 , which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2. Furthermore, the invention relates to novel intermediates, useful for the synthesis of compounds of formula I.

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula X: 7. The compound of claim 6 , where Ris H and Ris —CHCH.21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .22. The pharmaceutical composition of claim 21 , further comprising a therapeutic agent selected from adenosine receptor antagonists claim 21 , α-adrenergic receptor antagonists claim 21 , β-adrenergic receptor antagonists claim 21 , β-adrenergic receptor agonists claim 21 , dual-acting β-adrenergic receptor antagonist/α-receptor antagonists claim 21 , advanced glycation end product breakers claim 21 , aldosterone antagonists claim 21 , aldosterone synthase inhibitors claim 21 , aminopeptidase N inhibitors claim 21 , androgens claim 21 , angiotensin-converting enzyme inhibitors and dual-acting angiotensin-converting enzyme/neprilysin inhibitors claim 21 , angiotensin-converting enzyme 2 activators and stimulators claim 21 , angiotensin-II vaccines claim 21 , anticoagulants claim 21 , anti-diabetic agents claim 21 , antidiarrheal agents claim 21 , anti-glaucoma agents claim 21 , anti-lipid agents claim 21 , antinociceptive agents claim 21 , anti-thrombotic agents claim 21 , ATreceptor antagonists and dual-acting ATreceptor antagonist/neprilysin inhibitors and multifunctional angiotensin receptor blockers claim 21 , bradykinin receptor antagonists claim 21 , calcium channel blockers claim 21 , chymase inhibitors claim 21 , digoxin claim 21 , diuretics claim 21 , dopamine agonists claim 21 , endothelin converting enzyme inhibitors claim 21 , endothelin receptor antagonists claim 21 , HMG-CoA reductase inhibitors claim 21 , estrogens claim 21 , estrogen receptor agonists and/or antagonists claim 21 , monoamine reuptake inhibitors claim 21 , muscle relaxants claim 21 , natriuretic peptides and their analogs claim 21 , natriuretic peptide clearance receptor antagonists claim 21 , neprilysin inhibitors claim 21 , nitric oxide donors claim 21 , non ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula XII: 3. The compound of claim 2 , where Ris H and Ris selected from H and —CHCH.5. The compound of claim 4 , where Ris H and Ris selected from H and —CHCH.13. The compound of claim 12 , where Ris H and Ris selected from H claim 12 , —CHOC(O)CH claim 12 , —CHOC(O)OCHCH claim 12 , —CHOC(O)OCH(CH) claim 12 , and —C(O)CH[CH(CH)]—NHC(O)OCH.15. The compound of claim 14 , where R is —CH claim 14 , Ris H claim 14 , and Ris selected from —CHOC(O)CH claim 14 , —CHOC(O)OCH(CH) claim 14 , —CHOC(O)OCHCH claim 14 , and —CHOC(O)CH[CH(CH)]—NHC(O)OCH.19. The compound of claim 18 , where Ris H and Ris selected from —CHOC(O)OCHCHand —CHOC(O)CH[CH(CH)]—NHC(O)OCH.21. The compound of claim 20 , where Ris H claim 20 , Ris —CHOP(O)(OH)or —CHOC(O)CH[CH(CH)]NH claim 20 , and Ris —CHCH; or Ris —C(O)CH[CH(CH)]NH claim 20 , Ris H claim 20 , and Ris —CHCH.23. The compound of claim 22 , where R claim 22 , R claim 22 , and Rare H; or Rand Rare H claim 22 , and Ris —CHOC(O)OCHCH.25. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .26. The pharmaceutical composition of claim 25 , further comprising a therapeutic agent selected from adenosine receptor antagonists claim 25 , α-adrenergic receptor antagonists claim 25 , β-adrenergic receptor antagonists claim 25 , β-adrenergic receptor agonists claim 25 , dual-acting β-adrenergic receptor antagonist/α-receptor antagonists claim 25 , advanced glycation end product breakers claim 25 , aldosterone antagonists claim 25 , aldosterone synthase inhibitors claim 25 , aminopeptidase N inhibitors claim 25 , androgens claim 25 , angiotensin-converting enzyme inhibitors and dual-acting angiotensin-converting enzyme/neprilysin inhibitors claim 25 , angiotensin-converting enzyme 2 activators and stimulators claim 25 , angiotensin-II vaccines claim 25 , anticoagulants claim 25 , anti-diabetic agents claim 25 , antidiarrheal agents claim 25 , anti- ...

TETRAZOLE COMPOUNDS AND METHODS OF MAKING AND USING SAME

Described herein are tetrazole compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tetrazole compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2. 2. The compound of claim 1 , wherein A is phenyl.3. The compound of claim 1 , wherein B is a bond.4. The compound of claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , halogen claim 1 , cyano claim 1 , hydroxyl claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccycloalkyl claim 1 , Calkoxy claim 1 , Calkenyloxy claim 1 , and Calkynyloxy claim 1 , wherein Calkenyl claim 1 , Calkynyl claim 1 , Calkenyloxy claim 1 , and Calkynyloxy are each independently optionally substituted by one or more substituents each independently selected from R claim 1 , wherein Calkyl and Calkoxy are each independently optionally substituted by one or more substituents each independently selected from R claim 1 , wherein Ccycloalkyl is optionally substituted by one or more substituents each independently selected from R.5. The compound of claim 1 , wherein Ris selected from the group consisting of H or Calkyl.6. The compound of claim 1 , wherein Ris H.7. The compound of claim 1 , wherein Ris selected from the group consisting of halogen claim 1 , cyano claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccycloalkyl claim 1 , Calkoxy claim 1 , Calkenyloxy claim 1 , Calkynyloxy claim 1 , Ccycloalkyloxy claim 1 , Calkyl-S(O)— claim 1 , Ccycloalkyl-Calkyl- claim 1 , and Ccycloalkyl-Calkoxy- claim 1 , wherein Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Calkoxy claim 1 , Calkenyloxy claim 1 , and Calkynyloxy are each independently optionally substituted by one or more substituents each independently selected from halogen claim 1 , hydroxyl claim 1 , RRN— claim 1 , or cyano claim 1 , wherein Ccycloalkyl and Ccycloalkoxy are each independently optionally ...

Tetrazole compounds for reducing uric acid

Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula I. The uric acid-lowering effects of the compounds of this invention are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, cognitive impairment, early-onset essential hypertension, and Plasmodium falciparum -induced inflammation.

PROCESS AND INTERMEDIATE COMPOUNDS USEFUL IN THE PREPARATION OF STATINS

There is provides a process for the preparation of a compound of formula (7): wherein R is an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; provides that R is not a compound of Formula (a): wherein Rrepresents an alkyl group, such as a Calkyl group, and preferably an isopropyl group; Rrepresents an aryl group, preferably a 4-fluorophenyl group; Rrepresents hydrogen, a protecting group or an alkyl group, such as a Calkyl group, and preferably a methyl group; and Rd represents hydrogen, a protecting group or a SORgroup where Ris an alkyl group, such as a Calkyl group, and preferably a methyl group. 17-. (canceled)9. The process of wherein Y is Cl or Br.11. The process of claim 10 , wherein Ris an alkyl group and/or Ris an alkanoyl group.12. The process of claim 11 , wherein Ris a Calkyl group and/or Ris a Calkanoyl group.13. The process of claim 12 , wherein Ris a —C(O)CH(Me)CHCHor —C(O)C(Me)CHCHgroup14. The process of claim 10 , wherein Ris an alkanoyl group.15. The process of claim 14 , wherein Ris a Calkanoyl group16. The process of claim 14 , wherein Ris a —C(O)CH(Me)CHCHor a —C(O)C(Me)CHCHgroup.17. The process of claim 10 , wherein Ris a substituted or unsubstituted aryl group and/or Ris a substituted or unsubstituted alkyl group.18. The process of claim 17 , wherein Ris a 4-fluorophenyl group and/or Ris a cyclopropyl group.19. The process of claim 10 , wherein Ris a substituted or unsubstituted aryl group and/or Ris a substituted or unsubstituted alkyl group.20. The process of claim 19 , wherein Ris a 4-fluorophenyl group and/or Ris an isopropyl group.21. The process of claim 10 , wherein Ris a substituted or unsubstituted aryl or a substituted or unsubstituted aromatic heterocyclic group; Ris a substituted or unsubstituted aryl group; and/or Ris a substituted or unsubstituted aryl group.22. The process of claim 21 , wherein Ris a methyltetrazoyl group; Ris a 4-fluorophenyl group; and/or Ris a 4-fluorophenyl group.23. ...

Compositions and Methods for Treating or Preventing Pneumovirus Infection and Associated Diseases

The present invention provides novel crystalline polymorphic forms of MDT-637, in particular, crystalline polymorphic forms with physicochemical properties specifically suited for drug production, amorphous formation, composite form, and methods of preparation thereof. The novel polymorphs described herein are useful for the treatment of respiratory disease, such as disease caused by respiratory syncytial virus. 1. A composition comprising a polymorph of MDT-637.2. The composition of claim 1 , wherein the polymorph of MDT-637 comprises a crystal form of P-3 dihydrate claim 1 , P-3 ethanolate claim 1 , P-3 monohydrate claim 1 , P-3 anyhydrous claim 1 , P-2 anhydrous claim 1 , P-4 claim 1 , P-6 claim 1 , P-7 or P-8.3. The composition of claim 1 , comprising an amorphous form of P-3 dihydrate claim 1 , P-3 ethanolate claim 1 , P-3 monohydrate claim 1 , P-3 anyhydrous claim 1 , P-2 anhydrous claim 1 , P-4 claim 1 , P-6 claim 1 , P-7 or P-8.4. The composition of claim 1 , optionally comprising one or more pharmaceutically acceptable carriers.5. The composition of claim 2 , wherein characteristic diffraction peaks of the hydrate crystal form of pattern P-2 are shown in .6. The composition of claim 2 , wherein characteristic diffraction peaks of the monohydrate crystal form of pattern P-3 are shown in .7. The composition of claim 2 , wherein characteristic diffraction peaks of the dihydrate crystal form of pattern P-3 are shown in .8. The composition of claim 2 , wherein characteristic diffraction peaks of the anhydrous crystal form of pattern P-2 are shown in .9. The composition of claim 2 , wherein characteristic diffraction peaks of the anhydrous crystal form of pattern P-3 are shown in .10. The composition of claim 2 , wherein characteristic diffraction peaks of the P-3 ethanolate crystal form are shown in .11. The composition of claim 2 , wherein characteristic diffraction peaks of the P-4 crystal form are shown in claim 2 , wherein characteristic diffraction peaks of ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 1. (canceled)2. The process of claim 18 , where X is selected from pyrazole claim 18 , imidazole claim 18 , triazole claim 18 , benzotriazole claim 18 , furan claim 18 , pyrrole claim 18 , tetrazole claim 18 , pyrazine claim 18 , thiophene claim 18 , oxazole claim 18 , isoxazole claim 18 , thiazole claim 18 , isothiazole claim 18 , oxadiazole claim 18 , thiadiazole claim 18 , pyridazine claim 18 , pyridine claim 18 , pyrimidine claim 18 , pyran claim 18 , benzimidazole claim 18 , benzoxazole claim 18 , benzothiazole claim 18 , pyridylimidazole claim 18 , and pyridyltriazole.3. The process of claim 2 , where X is selected from pyrazole claim 2 , triazole claim 2 , benzotriazole claim 2 , tetrazole claim 2 , oxazole claim 2 , isoxazole claim 2 , thiazole claim 2 , pyridazine claim 2 , pyrimidine claim 2 , and pyridyltriazole.4. The process of claim 18 , where Ris selected from —ORand —NRR claim 18 , where Ris H claim 18 , Ris H or —OH claim 18 , and Ris H.7. The process of claim 18 , where Ris H.8. The process of claim 18 , where Ris absent or is selected from H; halo; —Calkylene-OH; —NH; —Calkyl; —CF; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; ═O; —NO; —C(CH)═N(OH); phenyl optionally substituted with one or two groups independently selected from halo claim 18 , —OH claim 18 , —CF claim 18 , —OCH claim 18 , —NHC(O)CH claim 18 , and phenyl; naphthalenyl; pyridinyl; pyrazinyl; pyrazolyl optionally substituted with methyl; thiophenyl optionally substituted with methyl or halo; furanyl; and —CH-morpholinyl; and Ris H.10. The process of claim 18 , where Ris absent or is selected from H; halo; —Calkylene-OH; —Calkyl; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; —NHC(O)R; ═O; phenyl optionally substituted with one or two groups independently selected from halo claim 18 , —OH claim 18 , and —OCH; pyridinyl; and pyrazinyl; Ris —Calkyl; ...

Iminopropene compound and use thereof

The compound (I) or a salt thereof has an excellent controlling activity against pests. Then the compound (I) or a salt thereof is useful for an active ingredient of a pesticidal composition.

COMPOUNDS FOR INFLAMMATION AND IMMUNE-RELATED USES

The invention relates to compounds of structural formulas (I), (VII) and (XI): 2. The compound of claim 1 , wherein L is —NR—C(O)—.37-. (canceled)910-. (canceled)11. The compound of claim 8 , wherein L is —NHC(O)—.1219-. (canceled)2127-. (canceled)29. The compound of claim 28 , wherein Rand Rare each claim 28 , independently claim 28 , a halo.30. The compound of claim 29 , wherein Ris a lower alkyl claim 29 , a lower alkoxy claim 29 , a lower alkyl sulfanyl claim 29 , a lower alkylamino claim 29 , a lower dialkylamino claim 29 , or a halo.31. The compound of claim 30 , Ris a bioisostere of an ester claim 30 , amide claim 30 , or carboxylic acid.32. The compound of claim 31 , wherein Ris a 5-membered heteroaryl.33. The compound of claim 32 , wherein Ris an optionally substituted oxazolyl claim 32 , an optionally substituted thiazolyl claim 32 , an optionally substituted 1H-tetrazolyl claim 32 , an optionally substituted 1H-imidazolyl claim 32 , an optionally substituted [1 claim 32 ,2 claim 32 ,4]oxadiazolyl claim 32 , or an optionally substituted 4H-[1 claim 32 ,2 claim 32 ,4]-triazolyl.34. The compound of claim 30 , wherein Ris a halo claim 30 , —C(O)R claim 30 , —S(O)R claim 30 , —S(O)NR claim 30 , —S(O)OR claim 30 , —P(O)(OR) claim 30 , or —P(O)(R) claim 30 , wherein:{'sub': '9', 'Ris a lower alkoxy, lower alkyl sulfanyl, or an alkoxyalkoxy;'}{'sub': '11', 'R, for each occurrence, is independently, a lower alkyl; and'}{'sub': '12', 'R, for each occurrence, is independently, H or a lower alkyl.'}35. The compound of claim 30 , wherein Rand Rare each a fluoro group.3744-. (canceled)46. The compound of claim 45 , wherein L is —NR—C(O)—.4751-. (canceled)5354-. (canceled)55. The compound of claim 52 , wherein L is —NHC(O)—.57115-. (canceled)116. A pharmaceutical composition claim 1 , comprising a pharmaceutically acceptable carrier and a compound of and optionally further comprising one or more additional therapeutic agents.117119-. (canceled)120. A pharmaceutical ...

C-substituted, 1h-azoles for amphoteric, solvent-less proton conductivity

Disclosed herein are the compounds shown below. Also disclosed are methods of making the compounds. R 1 =—O—; R 2 =any alkyl chain; R 3 =—CH 3 , —CN, —COOCH 3 , -tetrazole, -imidazole, or -triazole; R 4 =—H or —R 5 ; R 5 =—H, -halogen, —C≡CH, or —C≡C—; n is a positive integer; and m is a positive integer.

DUAL-ACTING ANTIHYPERTENSIVE AGENTS

The invention is directed to compounds of formula I: 131-. (canceled)3354-. (canceled) This application claims the benefit of U.S. Provisional Application No. 60/899,264, filed on Feb. 2, 2007 and No. 60/901,531, filed on Feb. 15, 2007; the entire disclosures of which are incorporated herein by reference in their entirety.1. Field of the InventionThe present invention relates to novel compounds having angiotensin type 1 (AT) receptor antagonist activity and neprilysin-inhibition activity. The invention also relates to pharmaceutical compositions comprising such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat diseases such as hypertension.2. State of the ArtThe aim of antihypertensive therapy is to lower blood pressure and prevent hypertension-related complications such as myocardial infarction, stroke, and renal disease. For patients with uncomplicated hypertension (for example, no risk factors, target organ damage, or cardiovascular disease), it is hoped that reducing blood pressure will prevent development of cardiovascular and renal comorbidities, conditions that exist at the same time as the primary condition in the same patient. For those patients with existing risk factors or comorbidities, the therapeutic target is the slowing of comorbid disease progression and reduced mortality.Physicians generally prescribe pharmacological therapies for patients whose blood pressure cannot be adequately controlled by dietary and/or lifestyle modifications. Commonly used therapeutic classes act to promote diuresis, adrenergic inhibition, or vasodilation. A combination of drugs is often prescribed, depending upon what comorbidities are present.There are five common drug classes used to treat hypertension: diuretics, which include thiazide and thiazide-like diuretics such as hydrochlorothiazide, loop diuretics such as furosemide, and potassium-sparing diuretics such as triamterene; βadrenergic receptor blockers ...

Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto

The present invention relates to compounds of Formula I and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as single pharmaceutical agents or in combination with one or more additional pharmaceutical agents, such as, a DPP-IV inhibitor, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto. 3. The compound according to claim 1 , wherein Ar is selected from: aryl and heteroaryl; each optionally substituted with one or more substituents selected from: chloro claim 1 , cyano claim 1 , dimethylcarbamoyl claim 1 , cyclopropylsulfonyl claim 1 , fluoro claim 1 , imidazolyl claim 1 , methyl claim 1 , methylpyrazolyl claim 1 , methylsulfonyl claim 1 , pyrrolyl claim 1 , tetrazolyl claim 1 , triazolyl claim 1 , and trifluoromethylthio.4. The compound according to claim 1 , wherein Ar is selected from: 2-chloro-4-(methylsulfonyl)phenyl claim 1 , 2-fluoro-4-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 2-fluoro-4-(1H-1 claim 1 ,2 claim 1 ,4-triazol-1-yl)phenyl claim 1 , 2-fluoro-4-(1H-imidazol-1-yl)phenyl claim 1 , 2-fluoro-4-(1H-pyrrol-1-yl)phenyl claim 1 , 2-fluoro-4-(1H-tetrazol-1-yl)phenyl claim 1 , 2-fluoro-4-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-fluoro-4-(4H-1 claim 1 ,2 claim 1 ,4-triazol-4-yl)phenyl claim 1 , 2-fluoro-4-(4-methyl-1H-pyrazol-1-yl)phenyl claim 1 , 2-fluoro-4-(methylsulfonyl)phenyl claim 1 , 2-methyl-6-(methylsulfonyl)pyridin-3-yl claim 1 , 3-chloro-4-(methylsulfonyl)phenyl claim 1 , 4-(1H-1 claim 1 ,2 claim 1 ,4-triazol-1-yl)phenyl claim 1 , 4-(1H-tetrazol- ...

ANTIOXIDANT INFLAMMATION MODULATORS: C-17 HOMOLOGATED OLEANOLIC ACID DERIVATIVES

This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula: 614-. (canceled)15. The compound of claim 5 , wherein Y is alkanediylor substituted alkanediyl.1618-. (canceled)19. The compound of claim 5 , wherein Xis ORand Ris absent.20. The compound of claim 4 , wherein Xis hydrogen.21. The compound of claim 5 , wherein Ris —OH.2228-. (canceled)29. The compound of claim 5 , wherein Ris acylor substituted acyl.30. The compound of claim 29 , wherein Ris selected from the group consisting of —C(═O)OH claim 29 , —C(═O)OCH claim 29 , —C(═O)NHCH claim 29 , —C(═O)NHCHCH claim 29 , and —C(═O)NHCHCF.31. The compound of claim 5 , wherein Ris acyloxyor substituted acyloxy.3246-. (canceled)47. The compound of claim 5 , wherein Ris —CN.4850-. (canceled)51. The compound of claim 3 , wherein Ris absent.5253-. (canceled)54. The compound of claim 2 , wherein Rand Rare each methyl.55. The compound of claim 2 , wherein Rand Rare each hydrogen.56. The compound of claim 1 , wherein Rand Rare each hydrogen.57. The compound of claim 1 , wherein Rand Rare each methyl.58. (canceled)59. The compound of claim 5 , wherein the bond between carbons 9 and 11 is a single bond.60. The compound of claim 5 , wherein the bond between carbons 9 and 11 is a double bond.61137-. (canceled)138. A pharmaceutical composition comprising as an active ingredient a compound of and a pharmaceutically acceptable carrier.139146-. (canceled)147. A therapeutic method comprising administering a pharmaceutically effective amount of a compound of to a subject.148. The method of claim 147 , wherein the subject is a human.149. (canceled)150. A method of treating cancer in a subject claim 5 , comprising administering to the subject a pharmaceutically effective amount of a compound of .151173-. (canceled)174. A method of treating or preventing a disease with an inflammatory component in a subject claim 5 , comprising administering to the subject a pharmaceutically effective amount of a ...

S1P Receptors Modulators and Their Use Thereof

The invention relates to novel compounds that have SIP receptor modulating activity. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate SIP receptor modulating activity or expression, for example, autoimmune response. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate SIP receptor modulating activity or expression such as autoimmune response.

COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING OR PREVENTING PNEUMOVIRUS INFECTION AND ASSOCIATED DISEASES

Compounds, compositions and methods are provided for the prophylaxis and treatment of infections caused by viruses of the Pneumovirinae subfamily of Paramyxoviridae and diseases associated with such infection. 4. A compound according to claim 1 , selected from the group consisting of:2,2′-[[3-(2,2,2-Trifluoroethyl)phenyl]methylene]bis[4-[[(5-methyl-1H-tetrazol-1-yl)imino]methyl]]phenol;3-[[Bis[[5-(5-methyl-1H-tetrazol-1-yl)imino]methyl]-2-hydroxyphenyl]methylene]benzeneethanol, acetate ester;3-[[Bis[[5-(5-methyl-1H-tetrazol-1-yl)imino]methyl]-2-hydroxyphenyl]methylene]benzeneethanol;2,2′-[[3-(4-Morpholinyl)phenyl]methylene]bis[4-[[(5-methyl-1H-tetrazol-1-yl)imino]methyl]]phenol;2,2′-[[3-(1-Piperidinyl)phenyl]methylene]bis[4-[[(5-methyl-1H-tetrazol-1-yl)imino]methyl]]phenol;3-[[Bis[[5-(5-methyl-1H-tetrazol-1-yl)imino]methyl]-2-hydroxyphenyl]methylene]-N,N-bis(methoxyethyl)benzenesulfonamide;3-[[Bis[[5-(5-methyl-1H-tetrazol-1-yl)imino]methyl]-2-hydroxyphenyl]methylene]-N-(hydroxyethyl)-N-methylbenzenesulfonamide;3-[[Bis[[5-(5-methyl-1H-tetrazol-1-yl)imino]methyl]-2-hydroxyphenyl]methylene]benzenepropanol;{'b': '3', '2,2′-[[-(4-Morpholinylsulfonyl)phenyl]methylene]bis[4-[[(5-methyl-1H-tetrazol-1-yl)imino]methyl]]phenol;'}2,2′-[[3-(Methoxyethoxy)phenyl]methylene]bis[4-[[5-methyl-1H-tetrazol-1-yl)imino]methyl]]phenol;2,2′-[[[3-Bis(phenylmethyl)amino]phenyl]methylene]bis[4-[[(5-methyl-1H-tetrazol-1-yl)imino]methyl]]phenol;3-[[Bis[[5-(5-methyl-1H-tetrazol-1-yl)imino]methyl]-2-hydroxyphenyl]methylene]phenoxyethanol, acetate ester;3-[[Bis[[5-(5-methyl-1H-tetrazol-1-yl)imino]methyl]-2-hydroxyphenyl]methylene]-N-(acetoxyethyl)-N-methylbenzenesulfonamide;3-[[Bis[[5-(5-methyl-1H-tetrazol-1-yl)imino]methyl]-2-hydroxyphenyl]methylene]phenoxyethanol;2-Hydroxy-N-[[3-[bis[[5-(5-methyl-1H-tetrazol-1-yl)imino]methyl]-2-hydroxylphenyl]methylene]phenyl]-N-(methylethyl)acetamide;2-(Acetyloxy)-N-[3-[[bis[[5-(5-methyl-1H-tetrazol-1-yl)imino]methyl]-2-hydroxyphenyl]methylene]phenyl]-N- ...

VALSARTAN SALTS

The invention relates to new salts of valsartan or crystalline, also partly crystalline and amorphous salts of valsartan, the respective production and usage, and pharmaceutical preparations containing such a salt. 1. A magnesium salt of valsartan.2. The salt according to in crystalline form.3. The salt according to in partially crystalline form.4. The salt according to in amorphous form.5. A magnesium hexahydrate salt of valsartan.6. The hexahydrate according to claim 5 , characterised by(i) an X-ray powder pattern taken with a Guinier camera comprising the following interlattice plane intervals: d in [A]: 19.7±0.3, 10.11±0.2, 9.8±0.2, 7.28±0.1, 5.81±0.05, 5.68±0.05, 5.03±0.05, 4.88±0.05, 4.18±0.05, 4.08±0.05, 3.46±0.05; or(ii) an ATR-IR spectrum having the following absorption bands expressed in reciprocal wave numbers (cm 1): 3378 (m); 3274 (m); 2956 (m); 1619 (st); 1557 (m); 1464 (m); 1419 (m); 1394 (st); 1374 (m); 1175 (m); 836 (m); 820 (s); 766 (st); 751 (m); 741 (st); 732 (st).7. A salt according in the form of a solvate.8. A salt according in the form of a hydrate.9. A pharmaceutical composition comprising the salt according to and a pharmaceutically acceptable excipient or additive.10. The pharmaceutical composition according to claim 9 , further comprising at least one of the following:(i) HMG-Co-A reductase inhibitor or a pharmaceutically acceptable salt thereof,(ii) angiotensin converting enzyme (ACE) Inhibitor or a pharmaceutical acceptable salt thereof,(iii) calcium channel blocker or a pharmaceutically acceptable salt thereof,(iv) aldosterone synthase inhibitor or a pharmaceutical acceptable salt thereof,(v) aldosterone antagonist or a pharmaceutically acceptable salt thereof,(vi) dual angiotensin converting enzyme/neutral endopeptidase (ACE/NEP) inhibitor or a pharmaceutical acceptable salt thereof,(vii) endothelin antagonist or a pharmaceutical acceptable salt thereof,(viii) renin inhibitor or a pharmaceutical acceptable salt thereof, or(ix) ...

TETRAZOLONES AS INHIBITORS OF FATTY ACID SYNTHASE

Provided herein are tetrazolone FASN inhibitors of the formula (I): 2. The method of claim 1 , wherein L is a covalent bond.3. The method of claim 1 , wherein L is a divalent Chydrocarbon chain claim 1 , wherein one methylene unit of L is optionally and independently replaced with a divalent carbocyclyl claim 1 , divalent heterocyclyl claim 1 , divalent aryl or divalent heteroaryl group.4. The method of claim 1 , wherein Ris selected from —CN claim 1 , —NO claim 1 , —SOH claim 1 , —SOH claim 1 , —C(═O)R claim 1 , —COH claim 1 , —CHO claim 1 , —COR claim 1 , —C(═O)N(R) claim 1 , —C(═NR)OR claim 1 , —C(═NR)N(R) claim 1 , —C(═O)NRSOR claim 1 , —SON(R) claim 1 , —SOR claim 1 , —SOOR claim 1 , —S(═O)R claim 1 , —C(═S)N(R) claim 1 , —C(═O)SR claim 1 , —C(═S)SR claim 1 , —P(═O)R claim 1 , —P(═O)(R) claim 1 , —P(═O)N(R) claim 1 , —P(═O)(NR) claim 1 , —B(OR) claim 1 , —BR(OR) and tetrazolyl.5. The method of claim 4 , wherein Ris selected from —C(═O)R claim 4 , —COH claim 4 , —CHO claim 4 , —COR claim 4 , —C(═O)N(R) claim 4 , —C(═NR)OR claim 4 , —C(═NR)N(R) claim 4 , —C(═O)NRSOR claim 4 , —C(═S)N(R) claim 4 , —C(═O)SRand —C(═S)SR.6. The method of claim 5 , wherein Ris selected from —C(═O)R claim 5 , —COH claim 5 , —CHO claim 5 , and —COR.7. The method of claim 6 , wherein Ris —COH.8. The method of claim 1 , wherein Ris further substituted with the group:{'br': None, 'sup': 'E', '—R'}wherein:{'sup': E', 'B10', 'B11', 'B11', 'B12', 'B12', 'B10', 'B12', 'B10', 'B10', 'B11', 'B11', 'B10', 'B11', 'B10', 'B11', 'B11', 'B11', 'B10', 'B11', 'B10', 'B11', 'B11', 'B11', 'B11', 'B11', 'B11', 'B10', 'B10', 'B101', 'B10', 'B10', 'B10', 'B10', 'B10', 'B12', 'B11', 'B11', 'B11', 'B12', 'B11', 'B11', 'B12', 'B12', 'B12', 'B12, 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '3, 'Ris selected from halogen, —OH, —OR, —ON(R), —N(R), —N(OR)R, —SH, —SR, —SSR, —OC(═O)R, —OCOR, —OC(═O)N(R), —NRC(═O)R, —-—NRCOR, —NRC(═O)N(R), — ...

USE OF AGONISTS OF FORMYL PEPTIDE RECEPTOR 2 FOR TREATING DERMATOLOGICAL DISEASES

The present invention relates to a method for treating dermal inflammation and dermal diseases by local or systemic delivery, in a subject in need of such treatment, which comprises administering a pharmaceutical composition comprising a therapeutically effective amount of at least one agonist of Formyl peptide receptor 2 (FPR2). 4. The method of claim 1 , wherein the local delivery is topical dermal delivery.5. The method of claim 2 , wherein the local delivery is topical dermal delivery.6. The method of claim 3 , wherein the local delivery is topical dermal delivery.7. The method of claim 4 , wherein the pharmaceutical composition is in a form selected from the group consisting of a cream claim 4 , a lotion claim 4 , a gel claim 4 , a solution claim 4 , a spray claim 4 , a foam claim 4 , a suspension and an emulsion.8. The method of claim 5 , wherein the pharmaceutical composition is in a form selected from the group consisting of a cream claim 5 , a lotion claim 5 , a gel claim 5 , a solution claim 5 , a spray claim 5 , a foam claim 5 , a suspension and an emulsion.9. The method of claim 6 , wherein the pharmaceutical composition is in a form selected from the group consisting of a cream claim 6 , a lotion claim 6 , a gel claim 6 , a solution claim 6 , a spray claim 6 , a foam claim 6 , a suspension and an emulsion. This application is a continuation of U.S. patent application Ser. No. 16/566,682, filed Sep. 10, 2019, which is a continuation of U.S. patent application Ser. No. 15/490,127, filed Apr. 18, 2017, now U.S. Pat. No. 10,434,112, which is a continuation of U.S. patent application Ser. No. 14/196,155, filed Mar. 4, 2014, now abandoned, which claims the benefit of U.S. Provisional Patent Application Ser. No. 61/773,778 filed Mar. 6, 2013, which are herein incorporated by reference in their entireties and serve as the basis of a priority and/or benefit claim for the present application.The present invention relates to a method for treating dermal ...

Tetrazolones as a Carboxylic Acid Bioisosteres

The present disclosure provides compounds that include a tetrazolone derivative of a carboxyl group of an active agent. This disclosure also relates to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, and processes for preparing these compounds. 1. A compound comprising a tetrazolone derivative of a carboxyl group of an active agent.2. The compound of claim 1 , wherein the tetrazolone derivative comprises a tetrazolone or a substituted tetrazolone.4. The compound of claim 3 , wherein Ris hydrogen or alkyl.5. The compound of claim 1 , wherein the active agent is a therapeutically effective active agent.6. The compound of claim 1 , wherein the tetrazolone derivative is produced from the carboxyl group of the active agent.8. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.9. The pharmaceutical composition of claim 8 , further comprising a second active agent.10. A compound comprising a tetrazolone or substituted tetrazolone produced from a carboxyl group of an active agent.11. A method of treating a disease or disorder in a subject in need of treatment claim 8 , the method comprising administering to the subject a compound comprising a tetrazolone derivative of a carboxyl group of an active agent.12. The method of claim 11 , wherein the tetrazolone derivative comprises a tetrazolone or a substituted tetrazolone.14. The method of claim 13 , wherein Ris hydrogen or alkyl.15. The method of claim 11 , wherein the active agent is a therapeutically effective active agent.16. The method of claim 11 , wherein the tetrazolone derivative is produced from the carboxyl group of the active agent. This application claims priority pursuant to 35 U.S.C. §119(e) to the filing date of U.S. Provisional Application No. 62/107,948, filed Jan. 26, 2015, the disclosure of which is herein incorporated by reference.Tetrazole is an organic heterocyclic ...

Heterocyclic compounds useful as dual atx/ca inhibitors

wherein R1, R2, Y, X, W, m and n are as defined herein, compositions including the compounds and methods of using the compounds.

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) ...

N-SUBSTITUTED BENZAMIDES AND METHODS OF USE THEREOF

The invention provides novel compounds having the general formula: 3. The compound of wherein B is N and Ris absent.4. The compound of wherein B is C.5. The compound of wherein R claim 1 , Rand Rare each independently selected from H claim 1 , F claim 1 , or Cl.6. The compound of wherein Ris H claim 1 , F or Cl; Rand Rare each H; and Ris an optionally substituted group selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —CN claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Ccycloalkyl claim 1 , and Calkoxy.7. The compound of wherein Ris Calkyl claim 1 , Chaloalkyl claim 1 , Ccycloalkyl or —NRR.8. The compound of claim 7 , wherein Ris selected from the group consisting of methyl claim 7 , ethyl claim 7 , propyl claim 7 , trifluoromethyl claim 7 , difluoromethyl claim 7 , monofluoromethyl claim 7 , isopropyl and cyclopropyl.11. The compound of wherein Ris selected from the group consisting of: methyl claim 1 , ethyl claim 1 , tert-butyl claim 1 , dimethylamino claim 1 , methylamino claim 1 , amino claim 1 , morpholino claim 1 , azetidino claim 1 , imidazolyl claim 1 , 3-hydroxyazetidino claim 1 , 3-fluoroazetidino claim 1 , cyclopropyl claim 1 , pyrrolidinyl claim 1 , 3 claim 1 ,3-difluoroazetidino claim 1 , tert-butyl claim 1 , ethyl claim 1 , 2-methoxyethyl claim 1 , 3-methoxyazetidino claim 1 , 2-hydroxyethyl claim 1 , 3-hydroxypyrrolidinyl claim 1 , and N-methylimidazolyl.12. The compound of wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is an optionally substituted group selected from the group consisting of Calkylene claim 1 , Calkenylene or Calkynylene.13. The compound of claim 1 , wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)(CH)—CH— or —CHCHCHCH—.14. The compound of claim 13 , ...

IDO INHIBITORS

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention. 2. The compound according to wherein Rand Rare independently H claim 1 , Cto Calkyl claim 1 , Cto Calkoxy claim 1 , or join together to form cyclopropyl or cyclobutyl.3. The compound according to wherein Z is —NH— and Ris —SOR claim 1 , halo (C-Calkyl) claim 1 , thiazolyl or oxazolyl claim 1 , wherein Ris Cto Calkyl claim 1 , Cto Ccycloalkyl4. The compound according to wherein Z is O and Ris H.5. The compound according to wherein Ris —COR.6. The compound according to wherein Ris a 5 membered heterocycle containing from 1 to 4 heteroatoms selected from N claim 1 , O claim 1 , and S.7. The compound according to wherein Ris H and Ris —CORor —CONRR; Ris H claim 1 , and Ris phenyl claim 1 , pyridyl claim 1 , isoxazolyl claim 1 , thiadiazolyl claim 1 , indolinyl claim 1 , or benzyl claim 1 , wherein Rmay optionally be substituted with from 1 to 3 substituents selected from the group consisting of halo claim 1 , amino claim 1 , phenoxy claim 1 , benzoxy claim 1 , isoxalyl claim 1 , Cto Calkoxy claim 1 , Cto Calkyl claim 1 , halo-Cto Calkyl claim 1 , and CN.8. The compound according to wherein Ris Cto Ccycloalkyl optionally substituted with halo claim 1 , —OH or Cto Calkoxy; Cto Calkyl optionally substituted with halo claim 1 , —OH or phenyl claim 1 , wherein said phenyl is optionally substituted with Cto Chaloalkyl claim 1 , Cto Calkoxy claim 1 , halo or Cto Calkyl; Cto Calkenyl; Cto Calkoxy; or benzyl optionally substituted with Cto Calkyl claim 1 , halo claim 1 , Cto Calkoxy claim 1 , or haloalkyl.9. The compound according to wherein Ris a Cto Cheterocycloalkyl containing from 1 to 4 heteroatoms selected from O claim 1 , N or S.10. The compound ...

Substituted Aromatic Compounds and Pharmaceutical Uses Thereof

The present invention relates to substituted aromatic compounds of Formula I and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds in the prevention and/or treatment of various diseases and conditions in subjects, including the prevention or treatment of (i) blood disorders, (ii) renal disorders, a nephropathies, or renal disorder complications; (iii) inflammatory-related diseases; and/or (iv) oxidative stress related disorders. 2. The method of claim 1 , wherein Ris straight chain Calkyl claim 1 , Calkyl claim 1 , or C-Calkenyl; and Ris H claim 1 , halogen claim 1 , haloalkyl claim 1 , or OR.3. The method of claim 1 , wherein Ris independently chosen from: H claim 1 , halogen claim 1 , haloalkyl claim 1 , straight chain C-Calkyl claim 1 , or OR; and Ris independently chosen from: H claim 1 , halogen claim 1 , haloalkyl claim 1 , C-Calkyl claim 1 , or OR.4. The method of claim 1 , wherein Ris OR.5. The method of claim 1 , wherein the pharmaceutically acceptable salt is a base addition salt.6. The method of claim 5 , wherein the base addition salt is a metal counterion.7. The method of claim 6 , wherein the metal counterion is sodium claim 6 , magnesium claim 6 , calcium claim 6 , potassium or lithium.8. The method of claim 7 , wherein the metal counterion is sodium.11. The method of claim 1 , wherein the inflammatory-related disease is an immune mediated inflammatory disease or an autoimmune disease.12. The method of claim 1 , wherein the inflammatory-related disease is an autoimmune disease.13. The method of claim 1 , wherein the inflammatory-related disease is selected from the group consisting of arthritis claim 1 , systemic lupus erythematosus (SLE) claim 1 , ITP claim 1 , glomerulonephritis claim 1 , vasculitis claim 1 , psoriatic arthritis claim 1 , psoriasis claim 1 , Crohn's disease claim 1 , inflammatory bowel disease claim 1 , ankylosing spondylitis claim 1 , Sjögren's syndrome claim 1 , Still's disease ...

USE OF AGONISTS OF FORMYL PEPTIDE RECEPTOR 2 FOR TREATING DERMATOLOGICAL DISEASES

The present invention relates to a method for treating dermal inflammation and dermal diseases by local or systemic delivery, in a subject in need of such treatment, which comprises administering a pharmaceutical composition comprising a therapeutically effective amount of at least one agonist of Formyl peptide receptor 2 (FPR2). 2. The method according to claim 1 , wherein the FPR2 agonist is a compound selected from:1-(4-bromophenyl)-3-[4-ethyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]urea;1-(4-bromophenyl)-3-[4-ethyl-2,5-dioxo-4-(propan-2-yl)imidazolidin-1-yl]urea;1-(4-bromophenyl)-3-(4,4-diethyl-2,5-dioxoimidazolidin-1-yl)urea;1-(4-bromo-2-fluorophenyl)-3-(4,4-diethyl-2,5-dioxoimidazolidin-1-yl)urea;1-(4-bromophenyl)-3-(2,4-dioxo-1,3-diazaspiro[4.5]dec-3-yl)urea;1-(4-bromophenyl)-3-[4-methyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]urea;1-(4-bromophenyl)-3-[4-methyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]urea;1-(4-bromo-2-fluorophenyl)-3-[4-ethyl-2,5-dioxo-4-(propan-2-yl)imidazolidin-1-yl]urea;1-(4-bromophenyl)-3-[2,5-dioxo-4,4-di(propan-2-yl)imidazolidin-1-yl]urea;1-(4-bromophenyl)-3-(4,4-dicyclopropyl-2,5-dioxoimidazolidin-1-yl)urea;1-(4-bromophenyl)-3-[4-ethyl-2,5-dioxo-4-(propan-2-yl)imidazolidin-1-yl]urea;1-(4-bromophenyl)-3-[4-ethyl-2,5-dioxo-4-(propan-2-yl)imidazolidin-1-yl]urea;1-(4-bromo-2-fluorophenyl)-3-[4-ethyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]urea;1-(4-bromophenyl)-3-{4-[2-(furan-2-yl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;1-(4-bromophenyl)-3-{4-[2-(4-fluorophenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;1-(4-bromophenyl)-3-{4-[2-(3-fluorophenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;1-(4-bromophenyl)-3-{4-[2-(4-hydroxyphenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;1-(4-bromophenyl)-3-{4-methyl-2,5-dioxo-4-[2-(thiophen-2-yl)ethyl]imidazolidin-1-yl}urea;1-(4-bromo-2-fluorophenyl)-3-{4-[2-(4-hydroxyphenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;1-(4-bromophenyl)-3-{4-methyl-4-[2-(5- ...

TETRAZOLE BASED CORROSION INHIBITORS

Disclosed are corrosion inhibitor compounds and compositions useful for preventing or inhibiting corrosion of surfaces found in cooling water applications. In some embodiments, the surfaces may include mild steel, aluminum, brass, copper, galvanized steel, a copper alloy, admirality brass, or any combination thereof. Also disclosed are methods of using the compounds and compositions as corrosion inhibitors. In some embodiments, the corrosion inhibitor compounds and compositions are used in cooling water applications. 2. The composition of claim 1 , wherein{'sub': 6', '10', '2', '2', '1', '6', '1', '6', '1', '6', '2', '2', '1', '6, 'sup': 3', '4', '3', '4, 'L is C-C-alkylenyl substituted or unsubstituted with 1 to 3 substituents independently selected from the group consisting of —F, —Cl, —NO, —CN, —OH, —NH, C-Calkyl, C-Chaloalkyl, C-Calkoxy, —COR, and —CON(R), wherein Rand R, at each occurrence, are each independently selected from the group consisting of hydrogen and C-Calkyl.'}3. The composition of claim 1 , wherein L is unsubstituted C-C-alkylenyl.4. The composition of claim 1 , wherein L is C-C-alkylenyl substituted with one claim 1 , two claim 1 , or three tetrazolyl groups claim 1 , wherein said tetrazolyl groups are substituted or unsubstituted.5. The composition of claim 1 , wherein the compound of formula (II) is selected from the group consisting of:1,6-di(1H-tetrazol-5-yl)hexane (“HDTZ”);1,7-di(1H-tetrazol-5-yl)heptane (“HeDTZ”);1,8-di(1H-tetrazol-5-yl)octane (“ODTZ”); and5,5′,5″-(hexane-1,3,6-triyl)tris(1H-tetrazole) (“TCH-TZ”).6. The composition of claim 1 , further comprising one or more components claim 1 , each component independently selected from the group consisting of:a solvent;a tracer;a scale inhibitor;a dispersant;an acid; anda base.7. The composition of claim 1 , wherein the composition comprises about 40% by weight of one or more compounds of formula (II).8. The composition of claim 1 , wherein the composition is a stable water-based ...

COMPOUND FOR MODULATING DDAH AND ADMA LEVELS, AS WELL AS METHODS OF USING THEREOF TO TREAT DISEASE

Disclosed are compounds that can modulate DDAH and the amount of asymmetric dimethylarginine (ADMA) in a subject. Also provided are pharmaceutical compositions comprising these compounds, as well as methods of using these compositions to treat and/or prevent diseases associated with elevated or low levels of DDAH and ADMA. 2. The method of claim 1 , wherein Y is a substituted or unsubstituted aryl ring claim 1 , optionally wherein Y is selected from an oxazole ring claim 1 , a pyridinyl ring claim 1 , a thiazole ring claim 1 , and a thiophene ring.5. The method of claim 4 , wherein Xand Xarei) both CH;{'sub': '2', 'ii) independently O or CHor'}iii) together with the bond to which they are attached form a 3-membered carbocyclic ring.7. The method of claim 1 , wherein Xand Xtogether with the bond to which they are attached forms a 3-membered carbocyclic ring.8. (canceled)9. The method of wherein said composition is administered for treating or preventing a disease or condition associated with elevated levels of asymmetric dimethylarginine (ADMA) in a subject.10. The method of claim 9 , wherein the risk factors claim 9 , disease or condition includes hypertension claim 9 , heart failure claim 9 , pulmonary arterial hypertension claim 9 , erectile dysfunction claim 9 , coronary and peripheral arterial disease claim 9 , renal disease claim 9 , insulin resistance claim 9 , diabetes claim 9 , atrial fibrillation claim 9 , sickle cell disease claim 9 , organ damage claim 9 , sepsis claim 9 , renal failure claim 9 , endothelial dysfunction claim 9 , vascular disease claim 9 , or a combination thereof.11. The method of wherein said composition is administered for reducing fibrosis in a cell or tissue.1213-. (canceled)14. The method of claim 11 , wherein the fibrosis is associated with a fibrotic condition of the lung claim 11 , a fibrotic condition of the liver claim 11 , a fibrotic condition of the heart or vasculature claim 11 , a fibrotic condition of the kidney claim 11 , ...

DUAL-ACTING ANTIHYPERTENSIVE AGENTS

The invention is directed to compounds of formula I: 136-. (canceled)37. A method for treating hypertension , comprising administering to a patient a therapeutically effective amount of a compound having both ATreceptor-antagonizing activity and neprilysin enzyme-inhibiting activity.38. The method of claim 37 , wherein the compound has a pKvalue for binding to an ATreceptor greater than or equal to about 5.0 and a pICvalue for the inhibition of the neprilysin enzyme greater than or equal to about 5.0.39. The method of claim 38 , wherein the compound has a pKvalue greater than or equal to about 6.0.40. The method of claim 39 , wherein the compound has a pKvalue within the range of about 8.0-10.0.41. The method of claim 38 , wherein the compound has a pICvalue greater than or equal to about 6.0.42. The method of claim 41 , wherein the compound has a pICvalue within the range of about 7.0-10.0.43. (canceled)44. A method for treating heart failure claim 41 , comprising administering to a patient a therapeutically effective amount of a compound having both ATreceptor-antagonizing activity and NEP enzyme-inhibiting activity.45. The method of claim 44 , wherein the compound has a pKvalue for binding to an ATreceptor greater than or equal to about 5.0 and a pICvalue for the inhibition of the neprilysin enzyme greater than or equal to about 5.0.46. (canceled)47. A method of treating a patient suffering from a disease or disorder that is treated by antagonizing the ATreceptor and/or inhibiting the NEP enzyme claim 44 , comprising administering to a patient a therapeutically effective amount of a compound having both ATreceptor-antagonizing activity and NEP enzyme-inhibiting activity.48. The method of claim 47 , wherein the compound has a pKvalue for binding to an ATreceptor greater than or equal to about 5.0 and a pICvalue for the inhibition of the neprilysin enzyme greater than or equal to about 5.0.4954-. (canceled) This application claims the benefit of U.S. Provisional ...

NOVEL HETEROARYL BUTANOIC ACID DERIVATIVES

The present invention describes novel heteroaryl butanoic acid derivatives that are good drug candidates especially with regard to leukotriene A4 hydrolase (LTA4H). The present invention also relates to pharmaceutical compositions comprising said novel heteroaryl butanoic acid derivatives, methods of using said compounds in the treatment of various diseases and disorders, and processes for preparing the said novel compounds. 2. The compound of or a pharmaceutically acceptable salt thereof; wherein{'sub': '2', 'R1 is OH or NH;'}Y is O;X1, X2, X3 and X4 are selected from N, NH, C, CH and O with the proviso that at least two of X1, X2, X3 or X4 are N or NH; and{'sub': 1', '6', '1', '6, 'R2 is phenyl optionally being substituted by halogen, cyano, C-Calkyl optionally substituted by halogen, C-Calkoxy, or a 5-6 membered heteroaryl ring containing 1 to 3 heteroatoms selected from N, O and S; or'}{'sub': 1', '6, 'R2 is a 5-10 membered mono- or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from N, O and S said heteroaryl being optionally substituted by C-Calkyl optionally substituted by halogen, cyano or halogen.'}3. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Y is attached in the para-position of the phenyl moiety.4. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Y is attached in the meta-position of the phenyl moiety.5. The compound of or a pharmaceutically acceptable salt thereof; wherein{'sub': '2', 'R1 is OH or NH;'}{'sub': '2', 'Y is CH; X1, X2, X3 and X4 are N; and'}{'sub': 1', '6', '3', '6, 'R2 is C-Calkyl optionally substituted by phenyl; or C-Ccycloalkyl.'}10. The compound in accordance to claim 9 , or a pharmaceutically acceptable salt thereof; whereinR1 is OH;Y is O; andR2 is a pyridyl ring being optionally substituted by cyano or halogen.11. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein the compound is selected from:(R)-3-amino-4-(5-(4-(benzo[d] ...

Pyrrole compounds as granzyme b inhibitors

Pyrrole compounds as Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Method for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

Selective androgen receptor degrader (sard) ligands and methods of use thereof

This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including heterocyclic anilide rings and their synthetic precursors, R-isomers, and non-hydroxylated and/or non-chiral propanamides, and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Exo Olefin-Containing Nuclear Transport Modulators and Uses Thereof

The invention generally relates to nuclear transport modulators, e.g., CRM1 inhibitors, and, more particularly, to a compound represented by structural formula (I), or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of structural formula I, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment, modulation and/or prevention of physiological conditions associated with CRM1 activity.

Neprilysin inhibitors

In one aspect, the invention relates to compounds having the formula: where R 1 -R 6 , a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

COMPOUNDS CONTAINING S-N-VALERYL-N-{[2'-(1H-TETRAZOLE-5-YL)-BIPHENYL-4-YL]-METHYL}-VALINE AND (2R,4S)-5-BIPHENYL-4-YL-4-(3-CARBOXY-PROPIONYLAMINO)-2-METHYL-PENTANOIC ACID ETHYL ESTER MOIETIES AND CATIONS

A compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and one or more monovalent cations such as Na useful for the treatment of hypertension and/or heart failure. 1. An amorphous solid form of a compound comprising anionic (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine , anionic (2R ,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester , and sodium cations in a 1:1:3 molar ratio.2. A pharmaceutical composition comprising the amorphous solid form according to and at least one pharmaceutically acceptable excipient.3. A process for preparing the amorphous solid form according to claim 1 , the process comprising:dissolving (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine or a pharmaceutically acceptable salt thereof, and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester or a pharmaceutically acceptable salt thereof, in a first solvent to form a first solution;dissolving a sodium-containing compound in a second solvent to form a second solution;combining the first and second solutions to form a combined solution; anddrying the combined solution.4. The process according to claim 3 , wherein the first solvent is different from the second solvent.5. An amorphous solid form of a compound comprising anionic (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine claim 3 , anionic (2R claim 3 ,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester claim 3 , and sodium cations in a 1:1:3 molar ratio claim 3 , and water.6. A pharmaceutical composition comprising the amorphous solid form according to and at least one pharmaceutically acceptable excipient.7. A process for preparing the amorphous solid form according to claim 5 , the process comprising:dissolving (S)—N- ...

COMPOUNDS CONTAINING S-N-VALERYL-N-{[2'-(1H-TETRAZOLE-5-YL)-BIPHENYL-4-YL]-METHYL}-VALINE AND (2R,4S)-5-BIPHENYL-4-YL-4-(3-CARBOXY-PROPIONYLAMINO)-2-METHYL-PENTANOIC ACID ETHYL ESTER MOIETIES AND CATIONS

A compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and one or more monovalent cations such as Na+ useful for the treatment of hypertension and/or heart failure. 1. A glassy solid form of a compound comprising anionic (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine , anionic (2R ,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester , and sodium cations in a 1:1:3 molar ratio.2. A pharmaceutical composition comprising the glassy solid form according to and at least one pharmaceutically acceptable excipient.3. A process for preparing the amorphous solid form according to claim 1 , the process comprising:dissolving (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine or a pharmaceutically acceptable salt thereof, and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester or a pharmaceutically acceptable salt thereof, in acetone to form a first solution;dissolving a NaOH in water to form a second solution;combining the first and second solutions and stirring them to form a combined solution; andevaporating the combined solution to obtain a glassy solid.4. A pharmaceutical composition comprising a compound comprising anionic (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine claim 1 , anionic (2R claim 1 ,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester claim 1 , and sodium cations in a 1:1:3 molar ratio claim 1 , obtained by mixing the glassy solid form according to and at least one pharmaceutically acceptable excipient.5. A glassy solid form of a compound comprising anionic (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine claim 1 , anionic (2R claim 1 ,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula XII: 128-. (canceled)30. The compound of claim 29 , wherein Ris H.31. The compound of claim 29 , wherein Ris selected from H claim 29 , —CHCHand —CHCH(CH).32. The compound of claim 31 , wherein Ris —CHCH.33. The compound of claim 30 , wherein Ris —CHCH.34. The compound of claim 29 , wherein P is selected from H claim 29 , t-butoxycarbonyl claim 29 , trityl claim 29 , benzyloxycarbonyl claim 29 , 9-fluorenylmethoxycarbonyl claim 29 , formyl claim 29 , trimethylsilyl and t-butyldimethylsilyl.35. The compound of claim 34 , wherein P is H.36. The compound of claim 33 , wherein P is H.37. The compound of claim 29 , wherein Ris H.38. The compound of claim 29 , wherein Ris F.39. The compound of claim 36 , wherein Ris F.40. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluoro-biphenyl-4-yl)-2-hydroxypentanoic acid or a pharmaceutically acceptable salt thereof.41. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester or a pharmaceutically acceptable salt thereof.42. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo-[1 claim 29 ,3]dioxol-4-ylmethyl ester or a pharmaceutically acceptable salt thereof.43. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 2 claim 29 ,2 claim 29 ,3 claim 29 ,3 claim 29 ,3-pentafluoropropyl ester or a pharmaceutically acceptable salt thereof.44. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid butyryloxymethyl ester or a pharmaceutically acceptable salt thereof.45. A method of performing a coupling reaction claim 29 , comprising contacting the compound of with a ...

NOVEL COMPOUNDS AND COMPOSITIONS FOR INHIBITION OF FASN

The present invention relates to compounds and composition for inhibition of FASN, their synthesis, applications, and antidotes. An illustrative compound of the invention is shown below: 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a C-Chydroxyl-alkyl either unsubstituted or substituted with —CHor CHF.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a 5-membered cycloalkyl either unsubstituted or substituted with substituents selected from the group consisting of —R claim 1 , —OR claim 1 , —NHRand —NRR1.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a 3 membered cycloalkyl wherein said 3 membered cycloalkyl is either unsubstituted or optionally substituted with substituents selected from the group consisting of deuterium claim 1 , —R claim 1 , —OR claim 1 , —NHR claim 1 , and —NRR.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a 4 membered cycloalkyl wherein said 3 membered cycloalkyl is either unsubstituted or optionally substituted with substituents selected from the group consisting of deuterium claim 1 , —R claim 1 , —OR claim 1 , —NHR claim 1 , and —NRR.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a substituted or unsubstituted 9-membered 6 claim 1 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 heteroatoms and said heteroatoms are independently O claim 1 , S claim 1 , or N.7. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris a substituted or unsubstituted 9-membered 6 claim 2 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 2 , 2 claim 2 , 3 claim 2 , or 4 heteroatoms and said heteroatoms are independently O claim 2 , S claim 2 , or N.8. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , ...

INHIBITORS FOR THE B-CATENIN / T-CELL FACTOR PROTEIN-PROTEIN INTERACTION

Disclosed are inhibitors for the β-catenin/T-cell factor interaction. The inhibitors are selective for β-catenin/T-cell factor over β-catenin/cadherin and β-catenin/APC interactions. Methods of using the disclosed compounds to treat cancer are also disclosed. 2. The compound of claim 1 , wherein Lis C(O)OCHor C(O)O and Cyis H.3. The compound of claim 1 , wherein Lis CHCHC(O) or CHNHC(O).4. The compound of claim 1 , wherein Lis NHC(O) claim 1 , C(O)NH claim 1 , C(O)NHCH claim 1 , CHNHC(O) claim 1 , C(O)NHO claim 1 , ONHC(O) claim 1 , C(O)NHOCH claim 1 , or CHONHC(O).5. The compound of claim 1 , wherein Cyis phenyl substituted with one or more halo claim 1 , Calkyl claim 1 , Chaloalky claim 1 , Calkoxyl claim 1 , or amino.6. The compound of claim 1 , wherein Cyis pyridinyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , pyrrolyl claim 1 , isoxazolyl claim 1 , isothiazolyl claim 1 , oxazolyl claim 1 , thiazolyl claim 1 , pyranyl claim 1 , or furanyl claim 1 , any of which is optionally substituted with one or more halo claim 1 , Calkyl claim 1 , Chaloalky claim 1 , Calkoxyl claim 1 , or amino.7. The compound of claim 1 , wherein Cyis cyclopenyl claim 1 , cyclohexyl claim 1 , tetrahydropyranyl claim 1 , or tetrahydrofuranyl claim 1 , any of which is optionally substituted with one or more halo claim 1 , Calkyl claim 1 , Chaloalky claim 1 , Calkoxyl claim 1 , or amino.8. The compound of claim 1 , wherein Lis CH.9. The compound of claim 1 , wherein Aris phenyl substituted with one or more halo claim 1 , Calkyl claim 1 , Chaloalky claim 1 , Calkoxyl claim 1 , Chaloalkoxyl claim 1 , amino claim 1 , phenyl claim 1 , or morpholino.10. The compound of claim 1 , wherein Aris phenyl substituted with chloro claim 1 , fluoro claim 1 , or methyl.11. The compound of claim 1 , wherein Aris pyridinyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , pyrrolyl claim 1 , isoxazolyl claim 1 , isothiazolyl claim 1 , oxazolyl claim 1 , thiazolyl claim 1 , pyranyl claim 1 , or furanyl ...

INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE (IDO)

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention. 9. The compound according to wherein the ICin the HEK Human IDO-1 assay is <10 nM.10. A pharmaceutical composition comprising one or more compounds according to and a pharmaceutically acceptable carrier or diluent.11. (canceled)12. (canceled)13. (canceled)14. A method for the treatment of a disease selected from the group consisting of cancer claim 1 , viral infections claim 1 , depression claim 1 , organ transplant rejection and autoimmune disease in a patient comprising administering to said patient a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof according to .15. The method according to further comprising administering to the patient a therapeutically effective amount of at least one of an anti-viral agent claim 14 , a chemotherapeutic agent claim 14 , an immunosuppressant claim 14 , radiation claim 14 , an anti-tumor vaccine claim 14 , an antiviral vaccine claim 14 , cytokine therapy or a tyrosine kinase inhibitor prior to claim 14 , simultaneously with or after administration of the compound.16. A method of inhibiting the activity of indoleamine 2 claim 1 ,3-dioxygenase comprising contacting said indoleamine 2 claim 1 ,3-dioxygenase with a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.17. The method of claim 14 , wherein said disease is cancer.18. The method of wherein said cancer is selected from the group consisting of colon claim 17 , glioblastoma claim 17 , pancreatic claim 17 , breast claim 17 , prostate claim 17 , lung claim 17 , ovarian claim 17 , cervical claim 17 , renal claim 17 , head and neck claim 17 , lymphoma claim 17 , leukemia and melanoma.19. A ...

AUTOTAXIN INHIBITORS

The present invention relates to novel compounds that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in diseases and disorders mediated by autotaxin. 15-. (canceled)8. A pharmaceutical composition comprising a compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , and a pharmaceutically acceptable carrier.9. A pharmaceutical combination comprising a therapeutically effective amount of the compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , and one or more therapeutically active co-agent.1015-. (canceled)16. A method of treating an autotaxin dependent or an autotaxin mediated disease or condition wherein the disease or condition is idiopathic pulmonary fibrosis comprising administering to a subject a therapeutically effective amount of a compound according to . This application is a continuation of U.S. patent application Ser. No. 14/906,161, filed Jan. 19, 2016, which is a U.S. National Phase filing of International Application No. PCT/IB2014/063143 filed 16 Jul. 2014, which claims priority to EP Application No. EP13177061.2 filed 18 Jul. 2013, the contents of which are incorporated herein by reference in their entirety.The present invention relates to novel compounds that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in diseases and disorders mediated by autotaxin.Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase (ENPP2), is a secreted ectoenzyme known to possess lysophospholipase D activity (Umezu-Goto et al., 2002), and is responsible for producing the bioactive lipid mediator lysophosphatidic acid (LPA) by the hydrolysis of lysophosphatidylcholine (LPC) (Tokumura et al., 2002). LPA is highly implicated in the pathogenesis of a number of physio-pathological diseases, including cancer (Liu ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 14-. (canceled)5. The compound of claim 24 , where Ris selected from —ORand —NRR claim 24 , Ris H claim 24 , Ris H or —OH claim 24 , and Ris H.8. The compound of claim 24 , where Ris —NRR claim 24 , where Ris H and Ris H.9. The compound of claim 24 , where Ris H.1015-. (canceled)16. The compound of claim 24 , where a is 0; or a is 1 and Ris 3-chloro.17. The compound of claim 24 , where b is 0; orb is 1 and Ris 3′-chloro claim 24 , 3′-methyl claim 24 , or 2′-methoxy; or b is 2 and Ris 2′-fluoro-5′-chloro claim 24 , 2′ claim 24 ,5′-dichloro claim 24 , 2′-methyl-5′-chloro claim 24 , or 3′-chloro-5′-hydroxy.18. The compound of claim 24 , where the methylene linker on the biphenyl is substituted with 2 methyl groups.20. The compound of claim 24 , where{'sup': 1', '7, 'Ris —OR;'}{'sup': '2', 'Ris H;'}X is selected from pyrazole, triazole, benzotriazole, isoxazole, pyridazine, pyrimidine, and pyridyltriazole;{'sup': 3', '20', '21', '22', '23', '24, 'sub': 0-5', '1-6', '3', '3-7', '0-2', '1-6', '0-1', '3', '3, 'Ris selected from H; halo; —Calkylene-OH; —Calkyl; —CF; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; ═O; —C(CH)═N(OH); phenyl optionally substituted with one or two groups independently selected from halo, —OH, and —OCH; pyridinyl; pyrazinyl; and thiophenyl substituted with methyl or halo;'}{'sup': 4', '35', '3', '4, 'sub': 1-6', '1-2', '2', '2', '2', '1-3, 'Ris selected from H; —OH; —Calkyl; —Calkylene-COOR; —CHCH(OH)CHOH; pyridinyl; and phenyl optionally substituted with one halo group; or Rand Rare taken together to form -phenylene-O—(CH)—;'}{'sup': '5', 'a is 0; or a is 1 and Ris 3-chloro;'}{'sup': 6', '6, 'b is 0; or b is 1 and Ris 3′-chloro, 3′-methyl, or 2′-methoxy; or b is 2 and Ris 2′-fluoro-5′-chloro, 2′,5′-dichloro, 2′-methyl-5′-chloro, or 3′-chloro-5′-hydroxy;'}{'sup': '20', 'sub': '1-6', 'Ris —Calkyl;'}{'sup': '21', 'Ris H;'}{'sup': 22', '23', '22', ' ...

METHODS AND COMPOSITIONS FOR TREATING AMYLOID-RELATED DISEASES

Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease. 1232-. (canceled)234. The compound of claim 233 , wherein Ris hydrogen.235. The compound of claim 233 , wherein Ris straight chain alkyl.236. The compound of claim 233 , wherein Ris t-butyl.237. The compound of claim 233 , wherein Ris carbocyclic.238. The compound of claim 233 , wherein Ris C-Cbicycloalkyl.239. The compound of claim 233 , wherein said bicyclic fused ring group is indolyl.240. The compound of claim 233 , wherein Lis CHCHor absent.251. A method of treating or preventing an amyloid-related disease in a subject comprising administering to a subject in need thereof a compound of in an amount effective to treat or prevent an amyloid related disease.252. The method according to claim 251 , wherein said amyloid-related disease is Alzheimer's disease claim 251 , cerebral amyloid angiopathy claim 251 , inclusion body myositis claim 251 , macular degeneration claim 251 , MCI claim 251 , or Down's syndrome.253. The method according to claim 251 , wherein amyloid fibril formation or deposition claim 251 , neurodegeneration claim 251 , microglial inflammatory response claim 251 , or cellular toxicity is reduced or inhibited upon administration of said compound.254. The method according to claim 251 , wherein said amyloid-related disease is diabetes claim 251 , AA amyloidosis claim 251 , AL amyloidosis claim 251 , or hemodialysis related amyloidosis (βM).255. The method of claim 251 , wherein said subject has Alzheimer's disease claim 251 , Mild Cognitive Impairment claim 251 , or cerebral amyloid angiopathy claim 251 , and stabilization of cognitive function claim 251 , prevention of a further decrease in cognitive function claim 251 , or prevention claim 251 , slowing claim 251 , or stopping of disease progression occurs in said patient upon administration.256. A method for inhibiting amyloid deposition in a subject comprising administering ...

QUATERNARY AMMONIUM SALTS AS INHIBITORS OF TRIMETHYLAMINE PRODUCTION

Provided are compounds that can inhibit pathogenic, bacterial metabolite production and conjugates of the same. Also provided are pharmaceutical compositions comprising the same and methods of using the same. 5. The compound of claim 4 , wherein Ris Calkyl substituted with —O-(acylated sugar) and is optionally further substituted with oxo.6. The compound of or claim 4 , wherein Ris methyl.7. The compound of any one of claim 4 , claim 4 , and claim 4 , wherein Ris Calkyl.8. The compound of any one of - claim 4 , wherein Ris propargyl.9. The compound of claim 4 , wherein{'sup': '1', 'sub': '2-6', 'Ris Calkyl substituted with —O-(acylated sugar) and is optionally further substituted with oxo;'}{'sup': '2', 'Ris methyl;'}{'sup': '3', 'sub': '1-6', 'Ris Calkyl; and'}{'sup': '4', 'Ris propargyl.'}10. The compound of claim 4 , wherein{'sup': '1', 'sub': '2-6', 'Ris Calkyl substituted with isosorbide and is optionally further substituted with oxo and/or methene;'}{'sup': '2', 'Ris methyl;'}{'sup': '3', 'sub': '1-6', 'Ris Calkyl; and'}{'sup': '4', 'Ris propargyl.'}13. The compound of claim 4 , wherein{'sup': '1', 'sub': 3-4', '1-2, 'Ris Ccycloalkyl Calkyl;'}{'sup': '2', 'sub': '2-6', 'Ris Calkyl optionally substituted with one or two hydroxyl, oxo, and —O-(acylated sugar);'}{'sup': 1', '2', 's', 's, 'sub': 2', 'n, 'or Rand R, together with the nitrogen atom to which both are attached, combine to form a 4- or 5-membered heterocyclic ring optionally substituted with ethynyl or —(CH)—ORor an acylated sugar, wherein n is 0 or 1, Ris hydrogen or an acylated sugar;'}{'sup': '3', 'sub': '1-6', 'Ris Calkyl optionally substituted with a halogen or hydroxyl; and'}{'sup': '4', 'sub': '1-6', 'Ris Calkyl or propargyl.'}14. The compound of claim 13 , wherein Ris Ccycloalkyl Calkyl.15. The compound of or claim 13 , wherein Ris Calkyl optionally substituted with one or two hydroxyl groups.16. The compound of claim 13 , wherein Rand R claim 13 , together with the nitrogen atom to which both ...

SELECTIVE PHOTOACTIVATION OF AMINO ACIDS FOR SINGLE STEP PEPTIDE COUPLING

Disclosed herein are formulations, substrates, and arrays for amino acid and peptide synthesis on microarrays. In certain embodiments, methods for manufacturing and using the formulations, substrates, and arrays including one-step coupling, e.g., for synthesis of peptides in a C→N orientation are disclosed. In some embodiments, disclosed herein are formulations and methods for high efficiency coupling of biomolecules to a substrate. 113.-. (canceled)14. A method of attaching a coupling molecule to a substrate , comprising:obtaining a substrate comprising a plurality of amine groups for linking to a coupling molecule;contacting said substrate with a carboxylic acid activating formulation comprising: a carboxylic acid activating compound, wherein said compound is 1-(3-(diethylamino)-propyl)-4-(2-methoxyphenyl)-1,4-dihydro-5H-tetrazole-5-thione, a coupling molecule, and a solvent;selectively exposing said photoactive coupling formulation to light, thereby activating a carboxylic group of said coupling molecule at a selectively exposed area;coupling the activated carboxylic group of said coupling molecule to at least one of said plurality of amine groups at said selectively exposed area, wherein said coupling is performed multiple times at different selectively exposed areas on said substrate and wherein said coupling step has a coupling efficiency of at least 98.5%; andoptionally repeating said method to produce a desired polymer at said at least one carboxylic acid group.15. The method of claim 14 , wherein said coupling molecule is an amino acid.16. The method of claim 15 , wherein said amino acid has a protecting group attached to an amine group.17. The method of claim 16 , wherein said protecting group is Fmoc.18. A method of attaching a coupling molecule to a substrate claim 16 , comprising:obtaining a substrate comprising a plurality of amine groups for linking to a coupling molecule;contacting said substrate with a carboxylic acid activating formulation ...

COMPOUNDS AND METHODS FOR INDUCING CHONDROGENESIS

The present invention provides compounds and compositions for the amelioration of arthritis and joint injuries by inducing mesenchymal stem cells into chondrocytes. 2. The method of claim 1 , wherein{'sup': 1', '2', '2, '(a) Lis a bond, Lis —C(O)NH—, ring B is phenyl, Ris —CN or phenyl, and subscript m is 1, or'}{'sup': 1', '2', '1, 'sub': '2', '(b) Ris —C(O)OH, subscript n is 1, ring A is phenyl, Lis —C(O)NH—, and Lis a bond or —CH—, or'}{'sup': 1', '2', '2, 'sub': '2', '(c) each of ring A and ring B is phenyl, Ris —C(O)OH or combined with L, subscript n is 1, and at least one Ris selected from the group consisting of H, —CN and —COH.'}5. The method of claim 4 , wherein each Ris independently selected from the group consisting of —C(O)R claim 4 , —C(O)OR claim 4 , Calkyl-C(O)OR claim 4 , —NRC(O)OR claim 4 , —NRC(O)NRR claim 4 , —SOOR claim 4 , —SONRR claim 4 , —NRSOR claim 4 , and —CN.6. The method of claim 4 , wherein each Ris independently selected from the group consisting of —CH—C(O)OH claim 4 , —C(O)Me claim 4 , —NHC(O)NH claim 4 , —NHC(O)OMe claim 4 , —NHSOMe claim 4 , —SONH claim 4 , —SONHMe claim 4 , —SOH claim 4 , —C(O)OH claim 4 , and —CN.7. The method of claim 4 , whereinring A is phenyl; andsubscript n is 1.8. The method of claim 4 , whereinring A is selected from the group consisting of biphenyl and pyridyl, orsubscript n is 2.11. The method of claim 10 , wherein each Ris independently selected from the group consisting of H claim 10 , —CHNHCONH claim 10 , —CHNHCOOMe claim 10 , —CHNHMe claim 10 , —CHOPh claim 10 , 2-CN claim 10 , 4-CN claim 10 , —C(O)OH claim 10 , —CONHOH claim 10 , —OCF2H claim 10 , —POH claim 10 , —SOH claim 10 , phenyl claim 10 , pyridyl claim 10 , imidazole and tetrazole.13. The method of claim 12 , wherein{'sup': '2', 'sub': 2', '2', '2', '2', '2', '2', '2', '2, 'each Ris independently selected from the group consisting of H, Me, —Cl, —CHOH, —CHCHOH, —CHNH, —C(O)Me, —C(O)OH, —C(O)NH, —CN, morpoholine, 3,4-difluorophenyl and —SONH; ...

EPOXYEICOSATRIENOIC ACID ANALOGS AND METHODS OF MAKING AND USING THE SAME

Compounds and compositions comprising epoxyeicosatrienoic acid (EET) analogs that act as EET agonists and are useful as medications in the treatment of drug-induced nephrotoxicity, hypertension and other related conditions. Methods of making and using the compounds and compositions are further described. 5. A composition comprising a compound of and a pharmaceutically acceptable carrier.6. A method of reducing hypertension in a subject claim 1 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 1 , wherein hypertension in said subject is reduced.7. (canceled)8. (canceled)9. A method of reducing nephrotoxicity in a subject claim 1 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 1 , wherein nephrotoxicity in said subject is reduced.10. The method of claim 9 , wherein the nephrotoxicity is drug-induced.11. The method of claim 10 , wherein the nephrotoxicity is cisplatin-induced.12. (canceled)13. (canceled)14. A method of reducing cisplatin nephrotoxicity in a subject claim 1 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 1 , wherein cisplatin nephrotoxicity in said subject is reduced.15. (canceled)16. (canceled)17. A composition comprising a compound of and a pharmaceutically acceptable carrier.18. A method of reducing hypertension in a subject claim 4 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 4 , wherein hypertension in said subject is reduced.19. A method of reducing nephrotoxicity in a subject claim 4 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 4 , wherein nephrotoxicity in said subject is reduced.20. The method of claim 19 , wherein the nephrotoxicity is drug-induced.21. The method of claim 20 , wherein the nephrotoxicity is cisplatin-in-induced.22. A method of ...

Compounds that inhibit human DNA ligases and methods of treating cancer

Methods for treating cancer using compounds that inhibit human DNA ligases. Methods for using compounds that inhibit human DNA ligases to provide insights into the reaction mechanisms of human DNA ligases, for example to identify the human DNA ligase involved in different DNA repair pathways. Screening methods for compounds that inhibit human DNA ligases. 1. A method of treating cancer in a patient in need thereof comprising administering a therapeutically effective amount of at least one compound selected from the group consisting of Compounds of structural formulae I-XVI.2. A method of treating cancer in a patient in need thereof comprising administering a therapeutically effective amount of at least one compound selected from the group consisting of Compounds No. 1 , No. 25 , No. 43 , No. 64 , No. 67 , No. 82 , No. 93 , No. 105 , No. 113 , No. 122 , No. 151 , No. 184 , No. 189 , No. 190 , No. 197 , No. 209 , No. 213 and No. 215.3. The method of treating cancer of claim 2 , wherein at least one compound is selected from the group consisting of Compounds No. 43 claim 2 , No 64 claim 2 , No. 67 claim 2 , No. 82 claim 2 , No. 151 claim 2 , No. 184 claim 2 , No. 189 claim 2 , No. 190 and 213.4. The method of treating cancer of claim 2 , wherein said at least one compound is selected from the group consisting of Compounds No. 64 claim 2 , No. 67 claim 2 , No. 82 claim 2 , No. 151 claim 2 , No. 184 claim 2 , No. 187 and No. 189.5. The method of treating cancer of claim 2 , wherein said at least one compound is selected from the group consisting of Compounds No. 43 claim 2 , No. 82 claim 2 , No. 151 claim 2 , No. 184 claim 2 , No. 189 claim 2 , and No. 190.6. The method of treating cancer of claim 2 , wherein said at least one compound is selected from the group consisting of Compounds No. 64 claim 2 , No. 189 claim 2 , and No. 197.7. The method of treating cancer of claim 2 , wherein said at least one compound is selected from the group consisting of Compounds No. 67 ...

Isothiocyanate compound and application thereof

The present invention provides an isothiocyanate compound and its application. The compound is an aryl-substituted isothiocyanate compound that has a structure of the general formula I. The isothiocyanate compound of the present invention has very good solubility in water, far better inhibitory activity for XPO1 protein than other non-aryl substituted congeneric compounds, little side effects, and good biological safety and bioavailability, and is quite suitable for clinical application. Therefore, the isothiocyanate compound would have tremendous potential market space and economic benefits.

PHARMACEUTICAL COMPOSITION COMPRISING SACUBITRIL AND VALSARTAN

The present invention relates to a pharmaceutical composition comprising a physical mixture of sacubitril sodium and valsartan disodium, wherein the X-ray powder diffraction pattern of valsartan disodium comprises characteristic peaks at the following 2 theta (±0.2) angles: 4.70°, 9.29°, 22.34°, measured using a Cu Kα radiation. The invention further relates to the use of said pharmaceutical composition as medicament in the treatment of heart failure. 1. A pharmaceutical composition comprising a physical mixture of sacubitril sodium and valsartan disodium , wherein the X-ray powder diffraction pattern of valsartan disodium comprises characteristic peaks at the following 2 theta (±0.2) angles: 4.70° , 9.29° , 22.34° , measured using a Cu Kα radiation.2. The composition according to claim 1 , wherein the X-ray powder diffraction pattern of sacubitril sodium comprises characteristic peaks at the following 2 theta (±0.2) angles: 3.14° claim 1 , 6.25° claim 1 , 11.97° claim 1 , 12.73° claim 1 , 13.78° claim 1 , 16.50° claim 1 , 18.35° claim 1 , 19.93° claim 1 , 21.56° claim 1 , 23.75° claim 1 , 26.20° claim 1 , measured using a Cu Kα radiation.3. The composition according to containing one of the following combinations of amounts:(i) 25.6 mg sacubitril sodium and 28.3 mg valsartan disodium;(ii) 51.2 mg sacubitril sodium and 56.6 mg valsartan disodium; or(iii) 102.4 mg sacubitril sodium and 113.2 mg valsartan disodium.4. The composition according to claim 1 , wherein valsartan disodium has a particle size distribution Dequal to or less than 30 μm.5. The composition according to claim 1 , wherein sacubitril sodium has a particle size distribution Dequal to or less than 50 μm.6. The composition according to further comprising one or more diluents claim 1 , disintegrants claim 1 , glidants and lubricants; and wherein said composition is in the form of a tablet.7. The composition according to claim 6 , wherein the diluent is microcrystalline cellulose.8. The composition ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 128-. (canceled)29. (2R ,4R)-5-Biphenyl-4-yl-4-{[5-(3-carbamoylpyrrolidine-1-carbonyl)-2H-pyrazole-3-carbonyl]-amino}-2-hydroxy-pentanoic acid or a pharmaceutically acceptable salt thereof.30. (2R ,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[5-(4-hydroxypiperidine-1-carbonyl)-2H-pyrazole-3-carbonyl]-amino}-pentanoic acid or a pharmaceutically acceptable salt thereof.31. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.32. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.33. The pharmaceutical composition of claim 31 , further comprising an ATreceptor antagonist.34. The pharmaceutical composition of claim 32 , further comprising an ATreceptor antagonist.35. The pharmaceutical composition of claim 33 , wherein the ATreceptor antagonist is selected from abitesartan claim 33 , azilsartan claim 33 , azilsartan medoxomil claim 33 , benzyllosartan claim 33 , candesartan claim 33 , candesartan cilexetil claim 33 , elisartan claim 33 , embusartan claim 33 , enoltasosartan claim 33 , eprosartan claim 33 , EXP3174 claim 33 , fonsartan claim 33 , forasartan claim 33 , glycyllosartan claim 33 , irbesartan claim 33 , isoteoline claim 33 , losartan claim 33 , milfasartan claim 33 , olmesartan claim 33 , olmesartan medoxomil claim 33 , opomisartan claim 33 , pratosartan claim 33 , ripisartan claim 33 , saprisartan claim 33 , saralasin claim 33 , sarmesin claim 33 , TAK-591 claim 33 , tasosartan claim 33 , telmisartan claim 33 , valsartan claim 33 , and zolasartan.36. The pharmaceutical composition of claim 34 , wherein the ATreceptor antagonist is selected from abitesartan claim 34 , azilsartan claim 34 , azilsartan medoxomil claim 34 , benzyllosartan claim 34 , candesartan claim 34 , candesartan cilexetil claim 34 , elisartan claim 34 , embusartan claim 34 , enoltasosartan claim 34 , eprosartan claim 34 , EXP3174 claim 34 , ...

Benzamides and nicotinamides as syk modulators

The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as Non Hodgkin's Lymphoma.

Fumarate analogs and uses thereof

Aspects of the present disclosure include compounds that find use for the treatment of a variety of autoimmune and inflammatory diseases and disorders. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

NITRIFICATION INHIBITORS

The present invention relates to novel nitrification inhibitors of formula I. Moreover, the invention relates to the use of these novel nitrification inhibitors for reducing nitrification, as well as agrochemical mixtures and compositions comprising the nitrification inhibitors. Further encompassed by the present invention are methods for reducing nitrification comprising the treatment of plants, soil and/or loci with said nitrification inhibitors, and methods for treating a fertilizer or a composition by applying said nitrification inhibitor. 116-. (canceled)18: The compound of claim 17 , wherein in said compound of formula I claim 17 , A is phenyl or a 6-membered hetaryl claim 17 , preferably phenyl claim 17 , wherein the aromatic ring may in each case be unsubstituted or may be partially or fully substituted by substituents claim 17 , which are independently of each other selected from R.19: The compound of claim 17 , wherein in said compound of formula I claim 17 , Rand Rboth represent hydrogen.20: The compound of claim 17 , wherein in said compound of formula I claim 17 , Ris hydrogen claim 17 , C-C-haloalkyl or ethinylhydroxymethyl claim 17 , and preferably Ris hydrogen.21: The compound of claim 17 , wherein in said compound of formula I claim 17 , R claim 17 , if present claim 17 , is{'sup': a', 'b', 'c', '1', 'c', '1', 'c', '1', 'c', '1', 'a', 'b', '2', '1', '2', '1', 'a', 'b', 'g', 'd', 'e', 'f, 'sub': 2', '2', '1', '6', '2', '6', '1', '4', '1', '4', '2', '4', '1', '2', '2', '4, '(i) halogen, CN, NRR, OR, C(═Y)R, C(═Y)OR, C(═Y)SR, C(═Y)NRR, YC(═Y)R, YC(═Y)NRR, NRN═C(R)(R), S(═O)R, NO, C-C-alkyl, C-C- C-C-haloalkyl, C-C-alkoxy, C-C-alkynyl-C-C-hydroxyalkyl, C-C-alkynyloxy;'}{'sub': 2', '4', '2', '4', '1', '4', '2', '4, 'sup': 1', 'c', '2', '1', 'c, '(ii) C-C-alkenylene-C(═Y)R, C-C-alkenylene-Y—C(═Y)R, wherein the C-C-alkylene or C-C-alkenylene chain may in each case be unsubstituted or may be partially or fully substituted by CN or halogen;'}{'sup': 'h', '( ...

Metabotropic Glutamate Receptor Positive Allosteric Modulators (PAMS) and Uses Thereof

Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor positive allosteric modulators (PAMS), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds. 3. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': '1', 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'Lis absent, —CH—, —CHCH—, —CHCHCH—, or —CHCHCHCH—.'}4. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': '1', 'Lis absent.'}5. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sub': 1', '6, 'Z is halogen, or C-Calkyl.'}6. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sub': 3', '2', '3, 'Z is —CH, or —CHCH.'}9. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': 1', '4', '5, 'Ris —OH or —N(RR).'}10. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': '4', 'sub': 1', '6', '1', '6, 'X is —OH, —OR, C-Calkyl, or C-Cfluoroalkyl.'}11. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': 2', '4, 'sub': 1', '6', '1', '6, 'Ris hydrogen, halogen, —CN, —OH, —OR, substituted or unsubstituted C-Calkyl, or substituted or unsubstituted C-Cfluoroalkyl.'}12. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': '3', 'sub': 1', '6', '3', '6, 'Ris C-Calkyl, or C-Ccycloalkyl.'}13. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': '3', 'sub': 3', '2', '3', '2', '2', '3', '3', '2', '2', '2', '2', '3', '3', '2', '3', '2', '3', '2', '3', '3, 'Ris —CH, —CHCH, —CHCHCH, —CH(CH), —CHCHCHCH, —CH(CH)CHCH, —CHCH(CH), —C(CH), cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.'}14. The compound of any one of - , or a pharmaceutically acceptable salt thereof , ...

Inhibitor of indoleamine-2,3-dioxygenase (ido)

The present disclosure provides compounds of Formula (I). The compounds described herein may be useful in treating a disease associated with IDO, for example, cancer or an infectious disease (e.g., viral or bacterial infectious diseases). Also, provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.

SULFINYLAMINOBENZAMIDE AND SULFONYLAMINOBENZAMIDE DERIVATIVES

Provided is a compound of Formula (I): 25-. (canceled)6. The method of claim 1 , wherein Ris selected from the group consisting of: Calkyl claim 1 , —NRR claim 1 , 6-10 membered aryl claim 1 , 5-10 membered heteroaryl claim 1 , Ccycloalkyl claim 1 , and 4-12 membered heterocyclyl claim 1 , wherein each Calkyl claim 1 , 6-10 membered aryl claim 1 , 5-10 membered heteroaryl claim 1 , Ccycloalkyl claim 1 , and 4-12 membered heterocyclyl is further substituted with one or more Rgroups.7. The method of claim 1 , wherein Ris selected from the group consisting of: —H claim 1 , —CN claim 1 , —F claim 1 , methyl claim 1 , methoxy and Chaloalkoxy.8. The method of claim 7 , wherein Ris selected from the group consisting of: —H and —F.9. The method of claim 1 , wherein Ris selected from the group consisting of: —H claim 1 , halo claim 1 , —OH claim 1 , —CN claim 1 , Calkyl claim 1 , Calkoxy claim 1 , Chydroxyalkyl claim 1 , Cheteroalkyl claim 1 , —SF claim 1 , —S(O)R claim 1 , —S(O)(NH)R claim 1 , —S(O)(NR)R claim 1 , —S(O)(NH)NRR claim 1 , —S(O)(NR)NRR claim 1 , —NRSOR claim 1 , —NRS(O)NRR claim 1 , —NRC(O)NRR claim 1 , —NRC(O)OR claim 1 , —C(O)R claim 1 , —C(O)OR claim 1 , —C(O)NRR claim 1 , and —NO claim 1 , wherein each of the Calkyl claim 1 , Calkoxy claim 1 , Chydroxyalkyl claim 1 , and Cheteroalkyl claim 1 , is further substituted with one or more Rgroups.10. The method of claim 9 , wherein Ris selected from the group consisting of: —H claim 9 , —F claim 9 , —Cl claim 9 , —OH claim 9 , —CN claim 9 , —S(O)R claim 9 , —C(O)R claim 9 , —SF claim 9 , —NO claim 9 , Calkyl claim 9 , and Calkoxy claim 9 , and wherein said Calkyl or Calkoxy is optionally substituted with one or more —F claim 9 , and Ris selected from the group consisting of Calkyl claim 9 , Ccycloalkyl claim 9 , Chydroxyalkyl claim 9 , Cheteroalkyl claim 9 , wherein the Calkyl claim 9 , Ccycloalkyl claim 9 , Chydroxyalkyl claim 9 , and Cheteroalkyl claim 9 , are optionally substituted with one or more Rgroups ...

TETRAZOLE DERIVATIVES AS CYTOCHROME P450 INHIBITORS

According to the invention there is provided a compound of formula I, wherein Rand Rhave meanings given in the description, which compounds are useful in the treatment of skin disorders and other diseases. 2. The compound of Formula I according to claim 1 , wherein Ris a methyl group claim 1 , optionally substituted with one or more fluorine atoms.3. The compound of Formula I according to claim 1 , wherein Ris a carboxylic acid protecting group.4. The compound of Formula I according to claim 3 , wherein Ris said carboxylic acid protecting group and said carboxylic acid protecting group is selected from the group consisting of a Calkyl claim 3 , phenyl and benzyl.57.-. (canceled)10. The method of treatment according to claim 8 , wherein the condition is selected from a skin disorder; an undesirable growth or proliferation of cells; restenosis or thrombosis occurring upon the introduction of coronary stents; and inflammatory bowel disease.11. A pharmaceutical formulation comprising a compound of Formula I as defined in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , in admixture with a pharmaceutically acceptable adjuvant claim 1 , diluent claim 1 , excipient or carrier.12. A pharmaceutical formulation according to claim 9 , wherein said compound of Formula I is present in an amount of from 0.01 to 90% by weight of the formulation.13. A pharmaceutical formulation according to claim 12 , wherein said compound of Formula I is present in an amount of from 0.05 to 50% by weight of the formulation.14. A pharmaceutical formulation according to claim 13 , wherein said compound of Formula I is present in an amount of from 1 to 20% by weight of the formulation.15. A pharmaceutical formulation according to claim 9 , wherein the amount of the compound of Formula I in the formulation is sufficient to achieve serum levels of between about 1 pM and about 1 mM in a patient.16. A pharmaceutical formulation according to claim 15 , wherein the amount of the compound ...

Stable amorphous form of sacubitril valsartan trisodium complex and processes for preparation thereof

The present invention relates to stable amorphous form of sacubitril valsartan trisodium complex and its solid dispersion compounds, processes for their preparation and pharmaceutical composition comprising the same. The present invention also relates to an improved process for the preparation of sacubitril sodium and its use in the preparation of sacubitril valsartan trisodium complex.

METHOD FOR PREPARATION OF INSENSITIVE HIGH EXPLOSIVE

The present invention provides a method for the preparation of an insensitive high enthalpy explosive Dihydroxylammonium 5,5′-bistetrazole-1,1′-diolate (TKX-50) in the presence of N,N-dimethylformamide, N,N-dimethylacetamide, or N-Methyl-2-pyrrolidone as a solvent via a four-step, one-pot reaction route to obtain a final product after four reaction steps. The more dangerous intermediate diazidoglyoxime may be solved by the one-pot method without the need of isolation. Further, the cyclization reaction is carried out in the presence of dropwisely added concentrated sulfuric acid to replace hydrochloric gas so no hydrochloric gas generator is needed to greatly reduce the amount of waste acid so as to effectively reduce the cost by avoiding using hydrochloric gas steel cylinders which require much safety equipment. 1. A method for preparing an insensitive high enthalpy explosive via a four-step , one-pot reaction route , comprising:(A) performing a chlorination reaction: carrying out the chlorination reaction for 1˜4 hours when warming up to 25° C.˜50° C., after dissolving glyoxime in at least one of N,N-dimethylformamide, dimethylacetamide and N-methyl-2-pyrrolidone, then adding N-chlorosuccinimide to at least one of the N,N-dimethylformamide, the dimethylacetamide and the N-methyl-2-pyrrolidone with cooling to 0° C.˜10° C.;(B) performing an azidation reaction: adding sodium azide to at least one of the N,N-dimethylformamide, the dimethylacetamide and the N-methyl-2-pyrrolidone with cooling to −5° C.˜5° C. to carry out the azidation reaction for 3 hours at suitable temperature;{'sub': '2', '(C) performing a cyclization reaction: adding concentrated sulfuric acid to at least one of the N,N-dimethylformamide, the dimethylacetamide and the N-methyl-2-pyrrolidone to carry out the cyclization reaction for 14˜16 hours at suitable temperature before cooling and adding a 40% sodium hydroxide aqueous solution to adjust a pH value to obtain 1,1′-dihydroxy-5,5′-bistetrazole ...

CYCLOHEXYL GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (I) as follows: 3. The compound of wherein G is 2-fluoro-5-methoxyphenyl claim 2 , 2-ethoxy-5-fluoropyridin-4-yl claim 2 , or 5-fluoro-2-methoxypyridin-4-yl.4. The compound of wherein G is 2-fluoro-5-methoxyphenyl.5. The compound of wherein Ris selected from the group consisting of hydrogen claim 1 , methoxy claim 1 , and fluoro.6. The compound of wherein Ris selected from the group consisting of hydrogen claim 2 , methoxy claim 2 , and fluoro.7. The compound of wherein Ris hydrogen.8. The compound of wherein Ris selected from hydrogen claim 1 , methyl claim 1 , or isobutyl.9. The compound of wherein Ris hydrogen.10. The compound of wherein L is selected from the group consisting of{'sub': 2', '2', '2, 'OCH—, —(CH)—, and —CH═CH—.'}11. The compound of wherein L is —OCH—.12. The compound of wherein Ris cyclopropyl claim 1 , methylacetylenyl claim 1 , or ethoxy.13. The compound of wherein Ris Ccycloalkyl.14. The compound of wherein Ris cyclopropyl.15. The compound of wherein Ris hydrogen claim 1 , methyl claim 1 , or fluoro.16. The compound of wherein ring W is phenyl.17. The compound of wherein ring W is pyridinyl.18. The compound of wherein A is carboxy.1923-. (canceled)24. A compound selected from the group consisting of(S)-3-cyclopropyl-3-(3-(((1s,4R)-4-(2-fluoro-5-methoxyphenyl)cyclohexyl) methoxy)phenyl)propanoic acid;(S)-3-cyclopropyl-3-(3-(((1r,4S)-4-(2-fluoro-5-methoxyphenyl)cyclohexyl) methoxy)phenyl) propanoic acid;(S)-3-cyclopropyl-3-(3-(((1s,4R)-4-(2-fluoro-5-methoxyphenyl)-4-hydroxycyclohexyl) methoxy)phenyl)propanoic acid;3-cyclopropyl-3-(2-(((1r,4r)-4-(2-fluoro-5-methoxyphenyl)cyclohexyl)methoxy)pyridin-4-yl)propionic acid;3-cyclopropyl-3-(2-(((1 s,4s)-4-(2-fluoro-5-methoxyphenyl)cyclohexyl)methoxy)pyridin-4-yl)propionic acid;(S)-3-cyclopropyl-3-(3-(((1r,4S)-4-(2-fluoro-5- ...

Compound, method for producing compound, and method for purifying compound

The present invention provides a compound characterized by being represented by general formula (I): (wherein, A represents a halogen atom, alkyl group, haloalkyl group, alkoxy group, haloalkoxy group, alkylsulfonyl group, unsubstituted or substituted aryl group, cyano group or nitro group, n represents an integer of 0 to 5 (and A may be mutually the same or different when n is 2 or more), Y represents an alkyl group, M represents an alkaline metal or alkaline earth metal, and m represents an integer of 1 or 2).

MODULATORS OF SESTRIN-GATOR2 INTERACTION AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same. 131.-. (canceled)34. The method of claim 33 , wherein the pharmaceutically acceptable composition comprises a pharmaceutically acceptable carrier claim 33 , adjuvant claim 33 , or vehicle. The present invention relates to compounds and methods useful for modulating the Sestrin-GATOR2 interaction thereby selectively modulating mTORC1 activity indirectly. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that senses diverse environmental cues, such as growth factors, cellular stresses, and nutrient and energy levels. When activated, mTORC1 phosphorylates substrates that potentiate anabolic processes, such as mRNA translation and lipid synthesis, and limits catabolic ones, such as autophagy. mTORC1 dysregulation occurs in a broad spectrum of diseases, including diabetes, epilepsy, neurodegeneration, immune response, suppressed skeletal muscle growth, and cancer among others (Howell et al., (2013) Biochemical Society transactions 41, 906-912; Kim et al., (2013) Molecules and cells 35, 463-473; Laplante and Sabatini, (2012) Cell 149, 274-293).Many upstream inputs, including growth factors and energy levels, signal to mTORC1 through the TSC complex, which regulates Rheb, a small GTPase that is an essential activator of mTORC1 (Brugarolas et al., (2004) Genes & Development 18, 2893-2904; Garami et al., (2003) Molecular Cell 11, 1457-1466; Inoki et al., (2003) Genes & Development 17, 1829-1834; Long et al., (2005) Current Biology 15, 702-713; Sancak et al., (2008) Science (New York, N.Y.) 320, 1496-1501; Saucedo et al., (2003) Nature cell biology 5, 566-571; Stocker et al., (2003) Nature cell biology 5, 559-565; Tee et al., (2002) Proc ...

ALPHA-CINNAMIDE COMPOUNDS AND COMPOSITIONS AS HDAC8 INHIBITORS

The present invention relates to inhibitors of histone deacetylases, in particular HDAC8, that are useful for the treatment of cancer and other diseases and disorders, as well as the synthesis and applications of said inhibitors. 116-. (canceled)17. A method of treating cancer , neurological disease , inflammatory disease , autoimmune disease , infection , metabolic disease , hematological disease , or cardiovascular disease in a subject in need thereof , comprising administering to the subject an effective amount of a compound selected from:(E)-3-(2-((1H-benzo[d]imidazol-2-yl)amino)phenyl)-N-hydroxyacrylamide (I-1);(E)-N-hydroxy-3-(2-(((1-(2-methoxyethyl)-1H-benzo[d]imidazol-2-yl)methyl)amino)phenyl)acrylamide (I-2);(E)-N-hydroxy-3-(2-((1-(2-methoxyethyl)-1H-benzo[d]imidazol-2-yl)amino)phenyl)acrylamide (I-3);(E)-N-hydroxy-3-(2-(((6-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)methyl)amino)phenyl)acrylamide (I-4);(E)-N-hydroxy-3-(2-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)acrylamide (I-5);(E)-1-hydroxy-N-(2-(3-(hydroxyamino)-3-oxoprop-1-en-1-yl)phenyl)cyclobutane-1-carboxamide (I-6);(E)-N-hydroxy-3-(2-((3-(trifluoromethyl)phenyl)sulfonamido)phenyl)acrylamide (I-7);(E)-3-(2-(4-aminopiperidin-1-yl)phenyl)-N-hydroxyacrylamide (I-8);(E)-N-hydroxy-3-(2-(4-(2-(4-methoxyphenyl)acetamido)piperidin-1-yl)phenyl)acrylamide (I-9);(E)-3-(2-(4-(2-(4-chlorophenoxy)acetamido)piperidin-1-yl)phenyl)-N-hydroxyacrylamide (I-10);(E)-N-(1-(2-(3-(hydroxyamino)-3-oxoprop-1-en-1-yl)phenyl)piperidin-4-yl)-1,8-naphthyridine-2-carboxamide (I-11);(E)-N-(1-(2-(3-(hydroxyamino)-3-oxoprop-1-en-1-yl)phenyl)piperidin-4-yl)-1-methylazetidine-3-carboxamide (I-12);(E)-3-(2-(4-(2-(4-chlorophenyl)acetamido)piperidin-1-yl)phenyl)-N-hydroxyacrylamide (I-13);(E)-N-(1-(2-(3-(hydroxyamino)-3-oxoprop-1-en-1-yl)phenyl)piperidin-4-yl)-3-methylbenzamide (I-14);(E)-5-(4-chlorophenyl)-N-(1-(2-(3-(hydroxyamino)-3-oxoprop-1-en-1-yl)phenyl)piperidin-4-yl)-2-methylfuran-3-carboxamide (I-15);(E)-N-(1-(2-(3-( ...

SMALL MOLECULE INHIBITORS OF THE ANDROGEN RECEPTOR ACTIVITY AND/OR EXPRESSION AND USES THEREOF

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a piperazine (or similar) structure which function as antagonists of androgen receptor activity, and their use as therapeutics for the treatment of cancer (e.g., castration-resistant prostate cancer) and other conditions characterized with androgen receptor activity and/or androgen receptor expression.

COMPOUNDS FOR SUPPRESSING A PERIPHERAL NERVE DISORDER INDUCED BY AN ANTI-CANCER AGENT

The present invention provides a medicament that suppresses (or mitigates) various neurological symptoms caused by a peripheral nerve disorder induced by an anti-cancer agent. 1. A method for suppressing a peripheral nerve disorder induced by an anti-cancer agent, which comprises administering a compound represented by the formula (II):wherein{'sup': '1′', 'R is'}(1) an aliphatic hydrocarbon group optionally having substituent(s),(2) an aromatic hydrocarbon group optionally having substituent(s),(3) a heterocyclic group optionally having substituent(s),{'sup': 1a′', '1a′, '(4) a group represented by the formula: —OR wherein R is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s), or'}(5) a group represented by the formula:{'sup': 1b′', '1c′, 'wherein R and R are the same or different and each is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s),'}X is methylene, NH, a sulfur atom or an oxygen atom,Y is methylene optionally having substituent(s) or NH optionally having substituent(s),ring A′ is a 5- to 8-membered ring optionally having 1 to 4 substituents selected from the group consisting of(i) an aliphatic hydrocarbon group optionally having substituent(s),(ii) an aromatic hydrocarbon group optionally having substituent(s),{'sup': 2′', '2′, '(iii) a group represented by the formula: —OR wherein R is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s), and'}(iv) a halogen atom,Ar′ is an aromatic hydrocarbon group optionally having substituent(s),a group represented by the formula:is a group represented by the formula:s is an integer of 0 to 2,t is an integer of 1 to 3, andthe total of s and t is 4 or less;provided that when X is methylene, then Y should be methyleneoptionally having substituent(s),or a salt thereof or a prodrug thereof. This application is a Continuation of U.S. application Ser. No. 13/971,159, filed Aug. 20, 2013, which is a Continuation of U.S. ...

INHIBITOR OF INDOLEAMINE-2,3-DIOXYGENASE (IDO)

The present disclosure provides compounds of Formula (I). The compounds described herein may be useful in treating a disease associated with IDO, for example, cancer or an infectious disease (e.g., viral or bacterial infectious diseases). Also, provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein. 36-. (canceled)8. (canceled)9. (canceled)10. The compound of claim 1 , wherein Rand Rare joined to form a substituted or unsubstituted 3- to 6-membered carbocyclic ring claim 1 , or substituted or unsubstituted 3- to 8-membered heterocyclic ring.11. The compound of claim 1 , wherein Rand Rare joined to form a substituted or unsubstituted cyclopropyl claim 1 , substituted or unsubstituted cyclobutyl claim 1 , substituted or unsubstituted cyclopentyl claim 1 , or substituted or unsubstituted cyclohexyl ring.12. (canceled)13. (canceled)14. The compound of claim 1 , wherein Rand Rare each independently substituted or unsubstituted C-Calkyl claim 1 , substituted or unsubstituted C-Ccycloalkyl claim 1 , or substituted or unsubstituted 3- to 12-membered heterocyclyl.1620-. (canceled)2325-. (canceled)2730-. (canceled)32. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable excipient.33. A method of treating a disease associated with IDO claim 1 , the method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt thereof.34. The method of claim 33 , wherein the disease associated with IDO is cancer.35. The method of claim 33 , wherein the disease associated with IDO is cancer claim 33 , which is selected from the group consisting of lung cancer claim 33 , breast cancer claim 33 , ...

MODULATORS OF SESTRIN-GATOR2 INTERACTION AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same. 131.-. (canceled)33. A pharmaceutically acceptable composition comprising a compound according to and a pharmaceutically acceptable carrier claim 32 , adjuvant claim 32 , or vehicle.34. The composition according to in combination with an additional therapeutic agent. The present invention relates to compounds and methods useful for modulating the Sestrin-GATOR2 interaction thereby selectively modulating mTORC1 activity indirectly. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that senses diverse environmental cues, such as growth factors, cellular stresses, and nutrient and energy levels. When activated, mTORC1 phosphorylates substrates that potentiate anabolic processes, such as mRNA translation and lipid synthesis, and limits catabolic ones, such as autophagy. mTORC1 dysregulation occurs in a broad spectrum of diseases, including diabetes, epilepsy, neurodegeneration, immune response, suppressed skeletal muscle growth, and cancer among others (Howell et al., (2013) Biochemical Society transactions 41, 906-912; Kim et al., (2013) Molecules and cells 35, 463-473; Laplante and Sabatini, (2012) Cell 149, 274-293).Many upstream inputs, including growth factors and energy levels, signal to mTORC1 through the TSC complex, which regulates Rheb, a small GTPase that is an essential activator of mTORC1 (Brugarolas et al., (2004) Genes & amp; Development 18, 2893-2904; Garami et al., (2003) Molecular Cell 11, 1457-1466; Inoki et al., (2003) Genes & amp; Development 17, 1829-1834; Long et al., (2005) Current Biology 15, 702-713; Sancak et al., (2008) Science (New York, N.Y.) 320, 1496-1501; Saucedo et al., (2003) Nature cell biology 5, 566-571 ...

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 ...