НОВЫЕ ПРОИЗВОДНЫЕ 2,4-ДИОКСОПИРРОЛИДИНА И 2,4-ДИОКСОТЕТРАГИДРОФУРАНА И ЛЕКАРСТВЕННЫЕ СРЕДСТВА, СОДЕРЖАЩИЕ ИХ В КАЧЕСТВЕ АКТИВНОГО ИНГРЕДИЕНТА

Изобретение относится к новым 1-(бифенил-4-ил)метил-1Н-1, 2,4-триазольным соединениям и 1-(бифенил-4-ил)метил-4Н-1,2,4-триазольным соединениям, причем каждое из них имеет в качестве заместителя во 2'-положении (2, 4-диоксопирролидин-5-илиден)метил или (2,4-диоксотетрагидрофуран-5-илиден)метил и их соли. Благодаря их сильному антагонизму к рецептору ангиотензина 11 и антигипотензивному действию их можно использовать в качестве терапевтического агента при заболеваниях кровеносной системы, например гипертензии, или для лечения сердечной недостаточности. 3 с. и 6 з.п. ф-лы, 1 табл.

СРЕДСТВО, СНИЖАЮЩЕЕ СОДЕРЖАНИЕ ХОЛЕСТЕРИНА В СЫВОРОТКЕ КРОВИ, ИЛИ СРЕДСТВО ДЛЯ ПРЕДОТВРАЩЕНИЯ ИЛИ ТЕРАПИИ АТЕРОСКЛЕРОЗА

Изобретение относится к области фармакологии и медицины и касается средства, снижающего содержание холестерина в сыворотке крови, или средства для предотвращения или терапии атеросклероза, состоящего из сочетания соединения общей формулы 1 и ингибиторов биосинтеза холестерина, набора, включающего это средство, и способа снижения содержания холестерина в сыворотке крови или предотвращения или терапии атеросклероза. Изобретение обеспечивает эффективное снижение содержания холестерина в сыворотке крови и предотвращение или эффективное лечение атеросклероза. 3 н. и 10 з.п. ф-лы, 14 табл.

С-ГЛИКОЗИДНЫЕ ПРОИЗВОДНЫЕ И ИХ СОЛИ

Изобретение относится к новым соединениям - С-гликозидным производным и их солям где кольцо А представляет собой (1) бензольное кольцо, (2) пяти- или шестичленное моноциклическое гетероарильное кольцо, содержащее 1, 2 или 4 гетероатома, выбранных из N и S, за исключением тетразолов, или (3) ненасыщенный девятичленный бициклический гетероцикл, содержащий 1 гетероатом, представляющий собой О; кольцо В представляет собой (1) ненасыщенный восьми-девятичленный бициклический гетероцикл, содержащий 1 или 2 гетероатома, выбранных из N, S и О, (2) насыщенный или ненасыщенный пяти- или шестичленный моноциклический гетероцикл, содержащий 1 или 2 гетероатома, выбранных из N, S и О, (3) ненасыщенный девятичленный бициклический карбоцикл, или (4) бензольное кольцо; Х представляет собой связь или низший алкилен; где значения кольца А, кольца В и Х соотносятся таким образом, что (1) когда кольцо А представляет собой бензольное кольцо, кольцо В не является бензольным кольцом, или (2) когда кольцо А представляет ...

ПРОТИВОВИРУСНЫЕ СОЕДИНЕНИЯ И ИХ ПРИМЕНЕНИЯ

Изобретение относится к новым соединениям формулы (I) и их фармацевтически приемлемым солям, которые,, ингибируют гепатотропный вирус HCV и могут быть использованы при лечении вируса гепатита С. В формуле (I)Rвыбран из группы, состоящей извыбран из группы, состоящей из простой связи углерод-углерод и двойной связи углерод-углерод; R, R, R, R, Rи Rнезависимо выбраны из группы, состоящей из атома водорода, метила и защитной группы для азота, выбранной из Салкилсульфонила; Rпредставляет собой атом водорода; Rвыбран из группы, состоящей из атома галогена, Салкила и гетероциклила, выбранного из 5-членного гетероарила с 1-2 гетероатомами, выбранными из азота, кислорода и серы, где алкил необязательно является замещенным одним или более заместителями, независимо выбранными из группы, состоящей из атома галогена; и гетероциклил необязательно является замещенным Салкилом, Rвыбран из группы, состоящей из Салкила, Салкенила, Салкилокси и атома галогена, L обозначает связь и Rвыбран из группы, состоящей ...

АНАЛОГИ ПРОСТАГЛАНДИНОВ, СПОСОБ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ СЕЛЕКТИВНОЙ АГОНИСТИЧЕСКОЙ АКТИВНОСТЬЮ В ОТНОШЕНИИ РЕЦЕПТОРА EP4

Изобретение относится к аналогам простагландина формулы I: где А означает -СН2-СН2 или -СН=СН-, В отсутствует или означает фенил, Z означает -C(O)OR' или тетразол-5-ил, где R' означает водород или C1-С6алкил, m равно 1, 2, 3, 4, 5 или 6, R1 означает C1-С6 алкил, незамещенный фенил или фенил, замещенный по меньшей мере одним заместителем, выбранным из группы, включающей трифторметил, галоген, -Y-Ra, -Y-ORa и -Y-C(O)Ra, где Y означает химическую связь или C1-С3алкиленовую группу, a Ra означает C1-С6алкил, незамещенный фенил или фенил, замещенный по меньшей мере одним заместителем, выбранным из группы, включающей C1-С6алкил, C1-С6алкокси, трифторметил и галоген, при условии, что В означает фенил, a R3, R4, R5 и R6 одновременно не означают водород, или R1 означает незамещенный фенил или фенил, замещенный по меньшей мере одним заместителем, выбранным из группы, включающей трифторметил, галоген, -Y-Ra, -Y-ORa и -Y-C(O)Ra, где Y означает химическую связь или C1-С3алкиленовую группу, a Ra означает ...

ПРОИЗВОДНОЕ 1,2,4-ТРИАЗОЛОНА

Изобретение относится к производным 1,2,4-триазолона и их фармацевтически приемлемым солям. Соединения изобретения обладают антагонистической активностью в отношении рецептора V1b аргинина-вазопрессина. В формуле (1А):Rпредставляет Салкил (Салкил необязательно замещен одной-тремя группами, выбранными из группы, состоящей из гидрокси, атомов галогена, и Сциклоалкила), Сциклоалкил или 4-8-членный насыщенный гетероцикл, содержащий один гетероатом, выбранный из атома кислорода; Rпредставляет атом водорода; Rпредставляет фенил или пиридил (фенил или пиридил необязательно замещены одной или двумя группами, выбранными из группы, состоящей из Салкокси, атомов галогена, циано и Салкилсульфонила); Rи Rмогут быть одинаковыми или различными, и каждый представляет атом водорода или Cалкил (Салкил необязательно замещен одной гидрокси), или Rи Rнеобязательно, вместе с атомом азота, к которому они присоединены, образуют 4-8-членный насыщенный или ненасыщенный гетероцикл, необязательно содержащий один атом ...

МОДУЛЯТОРЫ ЯДЕРНЫХ РЕЦЕПТОРОВ

Изобретение относится к соединениям формулEI-5 и FQ, а также к их фармацевтически приемлемым солям. Технический результат – получены новые соединения, которые могут найти применение в медицине для лечения иммунологических патологических состояний. 4 н.п. ф-лы, 36 табл.

ПРОИЗВОДНЫЕ 3-АМИНОПИРРОЛИДИНА В КАЧЕСТВЕ МОДУЛЯТОРОВ РЕЦЕПТОРОВ ХЕМОКИНОВ

Изобретение относится к новым соединениям формулы I: !! его оптическим изомерам или смеси их оптических изомеров и фармацевтически приемлемым солям, где: ! его оптические изомеры или смесь его оптических изомеров и фармацевтически приемлемые соли, где: ! R1 независимо выбирают из группы, состоящей из арила, гетероарила, арилкарбоксамидо, гетероарилкарбоксамидо, арилокси, арилалкокси или ариламино, и где указанные группы арила, арилалкила или гетероарила могут быть замещены 0-3 заместителями R1a, где R1a независимо выбирают из группы, состоящей из галогена, алкила, алкенила, алкокси, алкоксиалкила, гидроксиалкила, моно-, ди- или тригалогеноалкила, моно-, ди- или тригалогеноалкокси, моно- или дизамещенного аминоалкила, аминокарбонила, моно- или дизамещенного аминоалкила, аминокарбонила, моно- или дизамещенного аминокарбонила, циклического аминокарбонила, алкилсульфонила, остатка этерифицированной карбоновой кислоты, арилкарбониламино, карбамата, R1b-арила или R1b-гетероарила, где ! R1b представляет ...

ПРОИЗВОДНЫЕ БЕНЗИМИДАЗОЛА В КАЧЕСТВЕ МОДУЛЯТОРОВ ROR-ГАММА

Изобретение относится к области органической химии, а именно к циклическому соединению формулы (I) или к его фармацевтически приемлемой соли, где X представляет собой –C(O)NH- или –NHC(O)-; R1выбран из (C1–C4)алкила, галоген(C1–C4)алкила, циклобутила, тетрагидрофуранила, (C1–C4)алкокси, -N((C1–C3)алкил)2, -(C1–C3)алкил-O-(C1–C2)алкила, -C(O)O(C1–C2)алкила и циклопропила, причем каждый из указанных циклобутила и циклопропила необязательно замещен C(=O)OMe, -CN или 1 галогеном; L2представляет собой CH2или CHMe; Cy1выбран из фенила, пиридила и пиперидинила, каждый из которых необязательно замещен 1-2 группами, которые независимо выбирают из R5; Cy2выбран из гетероциклических структур, указанных в п. 1, каждый из которых необязательно замещен 1-2 группами, которые независимо выбирают из R6; R5выбран из галогена, -CN, -ORc, -S(O)2NRdReи -SO2Rb; R6выбирают из галогена, оксо и (C1–C4)алкила; R7представляет собой водород, ORcили (C1–C3)алкил, необязательно замещенный ORc; R8, при наличии, представляет ...

ИНГИБИТОРЫ МАТРИКСНЫХ МЕТАЛЛОПРОТЕИНАЗ

Изобретение относится к новым соединениям формулы (Iа) или (Iб) или их фармацевтически приемлемым солям, обладающим свойствами ингибиторов матриксных металлопротеиназ (ММР). В формуле (Iа) или (1б) ! ! ! Т отсутствует: G1 и G2 каждый независимо представляет собой СН или N; A представляет собой С1-6алкил; В представляет собой связь; D представляет собой связь; Е представляет собой фенил, замещенный конденсированным гетероциклическим кольцом, представляющим собой азотсодержащее кольцо, которое возможно может быть замещено карбонильными группами; или замещенный 6-членный гетероарил или бициклический гетероарил, где второе кольцо в бициклической системе является бензольным кольцом, причем гетероарил представляет собой 5-6-членное кольцо, содержащее 1, 2 или 3 гетероатома азота, и гетероарил замещен 1, 2 и 3 группами, выбранными из оксо и C1-6алкила; R16 представляет собой C1-6алкил; R18 представляет собой галогено, циано, нитро, OR16, ОСF3, SR16 или COR16; m представляет собой 0 или целое число ...

ПРОИЗВОДНЫЕ 1,2,4-ТРИАЗИН-4-АМИНА

Изобретение относится к соединению формулы Iyd или его фармацевтически приемлемым солям. Соединения формулы Iyd обладают ингибирующей активностью в отношении Арецептора или Арецептора. В формуле IydВ представляет собой СуВВ; СуВВ представляет собой фенил, необязательно имеющий один или более заместителей R4c; R4b, R4b' и R4c представляют собой, в каждом случае независимо, атом галогена; CN; С1-8 алкил, который необязательно имеет один или более заместителей, выбранных из атомов галогенов, OR5a; С3-8 циклоалкил; Heta; OR8; N(R9f)(R9g); =O; rr2 равен 0-1; ss и tt равны, независимо в каждом случае, 0 или 1, при условии, что ss и tt не могут одновременно быть равны 0; L1 и L2 оба представляют собой одинарные связи; R8 представляет собой, в каждом случае независимо, С1-8 алкил, который необязательно имеет один или более заместителей, выбранных из атомов галогенов; Heta представляет собой, в каждом случае независимо, 3-6-членное гетероциклическое полностью насыщенное кольцо, и которое содержит ...

ДИКЕТОНЫ И ГИДРОКСИКЕТОНЫ В КАЧЕСТВЕ АКТИВАТОРА СИГНАЛЬНОГО ПУТИ КАТЕНИНА

Данное изобретение относится к соединениям или их фармацевтически приемлемым солям общей формулы I, где Rпредставляет собой;Rвыбирают из группы, состоящей из замещенного или незамещенного фенила и,и; иR, R, Rи Rвсе представляют собой Н, также к соединениям II и III. Изобретение также относится к фармацевтическим композициям на основе этих соединений, способу активации передачи сигнала Wnt, способам лечения заболеваний, связанных с сигнальной трансдукцией, и применению их для лечения таких заболеваний, как остеопороз и остеоартропатия; несовершенный остеогенез, дефекты костей, переломы костей, пародонтоз, отосклероз, заживление раны, черепно-лицевые дефекты, онколитическое заболевание костей, травматические повреждения мозга, относящиеся к дифференцировке и развитию центральной нервной системы, включающие болезнь Паркинсона, удар, ишемическое церебральное заболевание, эпилепсию, болезнь Альцгеймера, депрессивное состояние, биполярное расстройство, шизофрению; глазные заболевания, такие как ...

НОВЫЕ ЗАМЕЩЕННЫЕ БИАРИЛОВЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ ИНДОЛАМИН-2,3-ДИОКСИГЕНАЗЫ (IDO)

Изобретение относится к соединению формулы (I) или его фармацевтически приемлемой соли, которые обладают ингибирующей активностью по отношению к индоламин-2,3-диоксигеназе (IDO). В указанной формуле n представляет собой 1; p представляет собой 1; в каждом случае A представляет собой -CH=; M представляет собой -O-; R1 представляет собой пиридинил; где пиридинил необязательно замещен 1-3 заместителями, независимо выбранными из: (a) галогена, (b) -C3-8-циклоалкила, необязательно замещенного -OH, (e) -O-C1-8-алкила, необязательно замещенного 1-5 атомами галогена, (f) -O-C3-8-циклоалкила, (g) -C1-8-алкила, необязательно замещенного 1-4 заместителями, независимо выбранными из галогена, -OH, -NH2, (i) -C(O)-Rf, где Rf выбран из -OH, -NH2 и -NH-C1-8-алкила; R2 представляет собой фенил; где фенил необязательно замещен 1-3 заместителями, независимо выбранными из: (a) галогена, (c) -CN, (d) -O-C1-8-алкила, необязательно замещенного 1-3 атомами галогена, и (e) -C1-8-алкила, необязательно замещенного ...

ПРОИЗВОДНОЕ БЕНЗИМИДАЗОЛА, ФАРМАЦЕВТИЧЕСКИЙ СОСТАВ И СПОСОБ МОДУЛЯЦИИ ГАМКA - РЕЦЕПТОРНОГО КОМПЛЕКСА

Производное бензимидазола формулы 1, где R3 - остаток формулы (а), R11 - пиридил, имидазол, пиримидинил, фуранил, тиенил или тиазолил, возможно замещенный аминогруппой; один из R6 или R7 - водород, а другой представляет -CR'= NOR'', в котором каждый из R' и R'' - водород, алкил, алкенил или алкинил, или его фармацевтически приемлемая соль либо оксид или фармацевтическая композиция на его основе обеспечивает модуляцию ГАМКA-рецепторного комплекса центральной нервной системы живого организма. 3 с. и 5 з.п. ф-лы, 1 табл. 1 ил.

ПРОИЗВОДНЫЕ АМИНОПИРИДИНА В КАЧЕСТВЕ МОДУЛЯТОРОВ БОГАТОЙ ЛЕЙЦИНОМ ПОВТОРНОЙ КИНАЗЫ 2 (LRRK2)

... 1. Соединение формулы I:или его фармацевтически приемлемые соли, где:m составляет от 0 до 3;Х представляет собой -NR-; -O-; или -S(O)-, где r составляет от 0 до 2 и Rпредставляет собой водород или C-алкил;Rпредставляет собой C-алкил;Rпредставляет собой галоген; C-алкокси; циано; C-алкинил; C-алкенил; гало-С-алкил; гало-С-алкокси; С-циклоалкил, где часть С-циклоалкила возможно замещена C-алкилом; С-циклоалкил-С-алкил, где часть С-циклоалкила возможно замещена C-алкилом; тетрагидрофуранил; тетрагидрофуранил-С-алкил; ацетил; оксэтанил; или оксэтан-С-алкил;Rи Rнезависимо друг от друга представляют собой галоген; C-алкил; C-алкокси; С-циклоалкокси; гало-С-алкил; или гало-C-алкокси;или Rи Rвместе с атомами, к которым они прикреплены, могут образовывать пяти- или шестичленное кольцо, которое возможно включает один или два гетероатома, независимо выбранных из О, N и S, причем кольцо возможно замещено один или более раз R;Rпредставляет собой C-алкилсульфонил; или циано; иRпредставляет собой C-алкил ...

БЕТТА-ЛАКТАМЫ, СПОСОБ ПОЛУЧЕНИЯ УКАЗАННЫХ СОЕДИНЕНИЙ И СЫВОРОТОЧНЫЕ ГИПОХОЛЕСТЕРИНЕМИЧЕСКИЕ СРЕДСТВА, СОДЕРЖАЩИЕ ТАКИЕ СОЕДИНЕНИЯ

... 1. Соединения приведенной далее общей формулы (I) где А1, А3 и А4 представляют собой атом водорода, атом галогена, алкильную группу с одним-пятью атомами углерода, алкоксигруппу с одним-пятью атомами углерода, -COOR1, группу приведенной далее формулы (b) где R1 представляет собой атом водорода или алкильную группу с одним-пятью атомами углерода, или группу приведенной далее формулы (а) где R2 представляет собой группу -СН2ОН, группу -СН2ОС(О)-R1 или группу -СО2-R1; R3 представляет собой группу -ОН или группу -ОС(О)-R1; R4 представляет собой -(CH2)kR5(CH2)l-, где k и l равны 0, 1 или большему целому числу; k+l равно 10 или меньшему целому числу; R5 обозначает простую связь (-), -СН=СН-, -ОСН2-, карбонильную группу или -СН(ОН)-, и R4 соединяется с тетрагидропирановым кольцом посредством углерод-углеродной связи; один из А1, А3 и А4 в формуле (I) должен представлять собой группу вышеуказанной формулы (а), А2 представляет собой алкильную цепь с одним-пятью атомами углерода, алкоксильную цепь ...

2-АРИЛ-5-ГЕТЕРОЦИКЛИЛЦИКЛОГЕКСАН-1,3-ДИОНЫ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ГЕРБИЦИДОВ

... 1. Соединения формулы (I) !! в которой R1 обозначает метил, этил, н-пропил, изопропил, циклопропил, галогенметил, галогенэтил, галоген, винил, этинил, метоксигруппу, этоксигруппу, галогенметоксигруппу или галогенэтоксигруппу, ! R2 и R3 независимо обозначают водород, галоген, C1-С6-алкил, C1-C6-галогеналкил, C1-С6-алкоксигруппу, C1-С6-галогеналкоксигруппу, С2-С6-алкенил, С2-С6-галогеналкенил, C2-С6-алкинил, С3-С6-алкенилоксигруппу, С3-С6-галогеналкенилоксигруппу, С3-С6-алкинилоксигруппу, С3-С6-циклоалкил, C1-С6-алкилтиогруппу, C1-С6-алкилсульфинил, C1-С6-алкилсульфонил, C1-С6-алкилсульфонилоксигруппу, C1-С6-галогеналкилсульфонилоксигруппу, цианогруппу, нитрогруппу, фенил, фенил, содержащий в качестве заместителей C1-С4-алкил, C1-С3-галогеналкил, C1-С3-алкоксигруппу, C1-С3-галогеналкоксигруппу, цианогруппу, нитрогруппу, галоген, C1-С3-алкилтиогруппу, C1-С3-алкилсульфинил или C1-С3-алкилсульфонил, или гетероарил или гетероарил, содержащий в качестве заместителей C1-С4-алкил, C1-С3-галогеналкил ...

ИНГИБИТОРЫ МЕТАЛЛОПРОТЕИНАЗ

... 1. Соединение формулы I или его фармацевтически приемлемая соль или in vivo гидролизуемый эфир где X выбран из NR1, О, S; Y1 и Y2 независимо выбраны из О, S; Z выбран из NR2, О, S; m равно 0 или 1; А выбран из прямой связи, (С1-6)алкила, (С1-6)алкенила, (С1-6)галогеноалкила или (С1-6)гетероалкила, содержащего гетерогруппу, выбранную из N, О, S, SO, SO2, или содержащего две гетерогруппы, выбранные из N, О, S, SO, SO2 и разделенные по меньшей мере двумя атомами углерода; R1 выбран из Н, алкила, галогеноалкила; R2 выбран из Н, алкила, галогеноалкила; R3 и R6 независимо выбраны из Н, галогена (предпочтительно F), алкила, галогеноалкила, алкоксиалкила, гетероалкила, циклоалкила, арила, алкиларила, гетероалкил-арила, гетероарила, алкилгетероарила, гетероалкил-гетероарила, арилалкила, арил-гетероалкила, гетероарил-алкила, гетероарил-гетероалкила, бисарила, арил-гетероарила, гетероарил-арила, бисгетероарила, циклоалкила или гетероциклоалкила, содержащих от 3 до 7 кольцевых атомов, где алкильный ...

ПРОИЗВОДНЫЕ 1-ПРОПАНОЛА И 1-ПРОПИЛАМИНА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ГЛЮКОКОРТИКОИДНЫХ ЛИГАНДОВ

... 1. Соединение формулы (IA) где R1 означает арил, гетероарил или С5-С15циклоалкил, каждый из которых необязательно и независимо содержит от одного до трех заместителей, причем каждый заместитель группы R1 независимо означает C1-С5алкил, С2 -С5алкенил, С2-С5алкинил, С3-С8циклоалкил, гетероциклил, арил, гетероарил, C1-C5алкокси, С2-С5 алкенилокси, С2-С5алкинилокси, арилокси, ацил, С1-С5алкоксикарбонил, С1-С5алканоилокси, С1-С5алканоил, ароил, аминокарбонил, алкиламинокарбонил, диалкиламинокарбонил, аминокарбонилокси, С1-С5алкиламинокарбонилокси, С1-С5диалкиламинокарбонилокси, С3-С5циклоалкиламинокарбонилокси, С1-С5алканоиламино, С1-С5алкоксикарбониламино, С1-С5алкилсульфониламино, аминосульфонил, С1-С5алкиламиносульфонил, С1-С5диалкиламиносульфонил, галоген, гидрокси, оксо, карбокси, циано, трифторметил, трифторметокси, нитро или амино, причем атом азота необязательно независимо моно- или дизамещен группой С1-С5алкил или арил; или уреидо, причем каждый атом азота необязательно независимо замещен ...

ИНГИБИТОРА МЕТАЛЛОПРОТЕИНАЗ

... 1. Соединение формулы I или его фармацевтически приемлемая соль или in vivo гидролизуемый эфир где Х выбран из NR1, О, S; Y1 и Y2 независимо выбраны из О, S; Z выбран из NR2, О, S; m равно 0 или 1; А выбран из прямой связи, (С1-6)алкила, (С1-6)алкенила, (С1-6)галогеноалкила или (С1-6)гетероалкила, содержащего гетерогруппу, выбранную из N, О, S, SO, SO2, или содержащего две гетерогруппы, выбранные из N, О, S, SO, SO2 и разделенные по меньшей мере двумя атомами углерода; R1 выбран из Н, алкила, галогеноалкила; R2 выбран из Н, алкила, галогеноалкила; R3 и R6 независимо выбраны из Н, галогена (предпочтительно F), алкила, галогеноалкила, алкоксиалкила, гетероалкила, циклоалкила, арила, алкил-циклоалкила, алкил-гетероциклоалкила, гетероалкил-циклоалкила, гетероалкил-гетероциклоалкила, циклоалкил-алкила, циклоалкил-гетероалкила, гетероциклоалкил-алкила, гетероциклоалкил-гетероалкила, алкиларила, гетероалкил-арила, гетероарила, алкилгетероарила, гетероалкил-гетероарила, арилалкила, арил-гетероалкила ...

СОЕДИНЕНИЕ С-ФЕНИЛГЛИЦИТОЛА ДЛЯ ЛЕЧЕНИЯ ДИАБЕТА

... 1. Соединение C-фенилглицитола, представленное формулой (I), приведенной ниже, или его фармацевтически приемлемая соль или его гидрат ! ! где R1 и R2 являются одинаковыми или различными и представляют собой атом водорода, гидроксильную группу, C1-6 алкильную группу, C1-6 алкоксигруппу или атом галогена, !R3 является атомом водорода, C1-6 алкильной группой, C1-6 алкоксигруппой или атомом галогена, ! Y является C1-6 алкиленовой группой, -O-(CH2)n- (n представляет собой целое число, принимающее значения от 1 до 4) или C2-6 алкениленовой группой, при условии, что когда Z является -NHC(=NH)NH2 или -NHCON(RB)RC, n не равно 1, ! Z является -CONHRA, -NHC(=NH)NH2 или -NHCON(RB)RC, ! или ! где RA является ! C1-6 алкильной группой, замещенной 1-3 заместителями, выбираемыми из группы, состоящей из гидроксильной группы, аминогруппы и карбамоильной группы, ! RB является ! (1) атомом водорода, ! (2) C1-6 алкильной группой, которая может быть замещена 1-3 заместителями, выбираемыми из группы A, ! (3) C3 ...

ГЕТЕРОЦИКЛИЧЕСКИЕ ИНГИБИТОРЫ АСПАРТИЛПРОТЕАЗЫ

Настоящее изобретение относится к гетероциклическим соединениям формулы I или к их стереоизомеру, таутомеру или фармацевтически приемлемой соли или сольвату, где W означает -C(=S)- или -С(=O); Х означает -N(R5)-; U означает связь или -(C(R6)(R7))b-, где b равно 1; R1, R2 и R5 независимо выбраны из группы, включающей Н, алкил с 1-6 атомами углерода, алкенил с 2-6 атомами углерода, циклоалкил с 3-7 атомами углерода и другие радикалы, представленные в п.1 формулы изобретения; R3, R4, R6 и R7 независимо выбраны из группы, включающей Н, алкил с 1-6 атомами углерода, циклоалкил с 3-7 атомами углерода, циклоалкилалкил с 3-7 атомами углерода в циклоалкильной части и 1-6 атомами углерода в алкильной части и другие радикалы, представленные в п.1 формулы изобретения; R15, R16 и R17, указанные ниже, независимо выбраны из группы, включающей Н, алкил с 1-6 атомами углерода, алкенил с 2-6 атомами углерода, алкинил с 2-4 атомами углерода, циклоалкил с 3-7 атомами углерода, циклоалкилалкил с 3-7 атомами ...

ЛЕЧЕНИЕ ТУБЕРОЗНОГО СКЛЕРОЗА

... 1. Соединение формулы ! ! где R1 означает СН3 или С3-С6алкинил, ! R2 означает Н, -СН2-СН2-ОН или -CH2-CH2-O-(C1-C8)алкил, например, -СН2-СН2-O-СН2-СН3, ! а Х означает =O, (Н, Н) или (Н, ОН), ! при условии, что R2 не означает Н, если Х означает =O, a R1 означает СН3, ! или соединение АВТ578, соединение CCI779, соединение АР23573 или соединение TAFA-93 для применения при лечении нейрокожных заболеваний. ! 2. Соединение для применения по п.1, где соединение выбирают из соединения формулы I, как определено в п.1, соединения АВТ578 или соединения TAFA-93, и где применение выбирают из применения для лечения нарушений, опосредованных туберозно-склерозным комплексом, для стимулирования регрессии нарушений, опосредованных туберозно-склерозным комплексом, для лечения симптомов, связанных с нарушениями, опосредованными туберозно-склерозным комплексом, лечения заболеваний, связанных с состояниями, опосредованными туберозно-склерозным комплексом. ! 3. Соединение по п.1 для лечения нейрофиброматоза типа ...

СПОСОБ ПОЛУЧЕНИЯ ХИРАЛЬНЫХ 1,4-ДИЗАМЕЩЕННЫХ ПИПЕРАЗИНОВ

... 1. Способ стереоселективного получения соединения формулы III где R и R' каждый независимо друг от друга представляет собой С1-С3-алкильную группу; Ar представляет собой дигидробензодиоксинил, бензодиоксинил или фенил, необязательно замещенный до трехкратно заместителями, независимо друг от друга выбранными из галогена, метокси, галогенметила, дигалогенметила и тригалогенметила; включающий взаимодействие соединения формулы Ia где R' имеет определенные выше значения и соединения формулы Ib с получением соединения формулы II где R' имеет определенные выше значения, и дальнейшее взаимодействие соединения формулы II с ариламином Ar-NH2, где Ar имеет определенные выше значения, с получением соединения формулы III. 2. Способ по п.1, где указанный способ осуществляют в виде последовательного процесса без выделения соединения формулы II. 3. Способ по п.1 или 2, где соединение формулы III представляет собой по существу чистый S-энантиомер. 4. Способ получения соединения формулы IV где Ar и R имеют ...

ГРИЗЕОФУЛЬВИНОВОЕ СОЕДИНЕНИЕ

ЗАМЕЩЕННЫЕ БЕНЗОАЗЕПИНЫ В КАЧЕСТВЕ МОДУЛЯТОРОВ TOLL-ПОДОБНЫХ РЕЦЕПТОРОВ

... 1. Соединение формулы Iили его таутомер, энантиомер или соль, где в указанной формулеY представляет собой -(O)(CH)R;х выбирают из 0 и 1;у выбирают из 0, 1, 2 и 3;Rвыбирают из арила, гетероарила и насыщенного или частично насыщенного гетероцикла, при этом когда х равен 0, указанный арил или гетероарил замещен -C(O)NRRили Т;Rи Rвыбирают независимо из водорода и алкила, при этом указанный алкил необязательно замещен -C(O)О(CH)R, или Rи Rвместе с атомом азота, к которому они присоединены, образуют насыщенный гетероцикл;t выбирают из 0, 1, 2 и 3;Rвыбирают из циклоалкила и арила;Т выбирают из гетероцикла, -(CHR)OR, -(O)(CH)C(O)R, -OSORи -СН(ОН)СНОН;Rвыбирают из Н или -ОН;Rвыбирают из -ORи алкила;Rвыбирают из алкила и Н;Rвыбирают из алкила, -(CH)Rи водорода, при этом указанный алкил необязательно замещен галогеном, амином, алкиламином или диалкиламином;Rвыбирают из -ОН, алкила, CF, циклоалкила, гетероцикла, арила и гетероарила;u выбирают из 0 и 1;z выбирают из 1, 2 и 3;s выбирают из 1 и 2;Rвыбирают ...

ИНГИБИТОРЫ АКТИВНОСТИ КИНАЗЫ LRRK2

4-АМИНО-6-(ГЕТЕРОЦИКЛИЛ)ПИКОЛИНАТЫ И 6-АМИНО-2-(ГЕТЕРОЦИКЛИЛ)ПИРИМИДИН-4-КАРБОКСИЛАТЫ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ГЕРБИЦИДОВ

НОВЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ ГИСТОНДЕАЦЕТИЛАЗЫ 6 И СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ

СОЕДИНЕНИЕ ГРИЗЕОФУЛЬВИНА И ЕГО ФАРМАЦЕВТИЧЕСКОЕ ПРИМЕНЕНИЕ

НОВЫЕ ПИРИДАЗИНОНОВЫЕ ГЕРБИЦИДЫ

ПРОТИВОВИРУСНЫЕ СОЕДИНЕНИЯ И ИХ ПРИМЕНЕНИЯ

... 1. Соединение или его соль, гдеструктура соединения соответствует формуле (I)Rвыбран из группы, состоящей изарилкарбонила и гетероарилкарбонила;выбран из группы, состоящей из простой связи углерод-углерод и двойной связи углерод-углерод;R, R, R, R, R, Rи Rнезависимо выбраны из группы, состоящей из атома водорода, метила и защитной группы для азота;Rвыбран из группы, состоящей из атома водорода и метила;Rобозначает атом галогена;Rобозначает атом галогена;n выбран из группы, состоящей из 1, 2 и 3;Rвыбран из группы, состоящей из атома водорода, амино и защитной группы для азота, замещенной амино;m выбран из группы, состоящей из 0, 1, 2 и 3;Rвыбран из группы, состоящей из атома водорода, арила, алкила и алкилоксикарбонила;Rвыбран из группы, состоящей из атома галогена, алкила, алкенила, алкинила, нитро, циано, азидо, алкилокси, алкенилокси, алкинилокси, амино, аминокарбонила, аминосульфонила, алкилсульфонила, карбоциклила и гетероциклила, где(a) амино, аминокарбонил и аминосульфонил необязательно ...

N-ФЕНИЛ-ДИОКСО-ГИДРОПИРИМИДИНЫ, ИСПОЛЬЗУЕМЫЕ В КАЧЕСТВЕ ИНГИБИТОРА ВИРУСА ГЕПАТИТА С (HCV)

... 1. Соединение или его соль, где: ! это соединение соответствует по структуре формуле I ! ; ! выбрана из группы, состоящей из одинарной углерод-углеродной связи и двойной углерод-углеродной связи; ! R1 выбран из группы, состоящей из водорода, метила и азотзащищающей группы; ! R2 выбран из группы, состоящей из водорода, гало, гидрокси, метила, циклопропила и циклобутила; ! R3 выбран из группы, состоящей из водорода, гало, оксо и метила; ! R4 выбран из группы, состоящей из гало, алкила, алкенила, алкинила, нитро, циано, азидо, алкилокси, алкенилокси, алкинилокси, амино, аминокарбонила, аминосульфонила, алкилсульфонила, карбоциклила и гетероциклила, где: ! (a) амино, аминокарбонил и аминосульфонил необязательно замещены: ! (1) одним или двумя заместителями, независимо выбранными из группы, состоящей из алкила, алкенила, алкинила и алкилсульфонила, или ! (2) двумя заместителями, которые вместе с аминоазотом образуют однокольцевой гетероцикл, и ! (b) алкил, алкенил, алкинил, алкилокси, алкенилокси ...

ИНГИБИТОРЫ IAP

... 1. Соединение формулы I где R1 означает Н, C1-C4алкил, C1-C4алкенил, C1-C4алкинил или С3-С10циклоалкил, которые являются незамещенными или замещенными, R2 означает Н, C1-C4алкил, C1-C4алкенил, C1-C4алкинил или С3-С10циклоалкил, которые являются незамещенными или замещенными, R3 означает Н, -CF3, -C2F5, C1-C4алкил, C1-C4алкенил, C1-C4 алкинил, -СН2-Z, или R2 и R3 вместе с атомом азота образуют цикл het, Z означает Н, -ОН, F, Cl, -СН3, -CF3, -СН2Cl, -CH2F или -CH2OH, R4 означает С1-С16алкил с прямой или разветвленной цепью, С1-С16алкенил, С1 -С16алкинил или С3-С10циклоалкил; -(CH2)1-6-Z1, -(СН2)0-6-арил и -(CH2)0-6-het, причем алкил, циклоалкил и фенил являются незамещенными или замещенными, Z1 означает -N(R8)-C(O)-(C1-C10)алкил, -N(R8)-С(O)-(СН2 )1-6-(С3-С7)циклоалкил, -N(R8)-C(O)-(CH2)0-6-фенил, -N(R8)-C(O)-(CH2)1-6-het, -C(O)-N(R9 )(R10), -С(O)-O-(С1-С10)алкил, -С(O)-O-(СН2)1-6-(С3-С7)циклоалкил, -С(O)-O-(СН2)0-6-фенил, -C(O)-O-(CH2)1-6-het; -O-С(O)-(С1-С10)алкил, -O-С(O)-(СН2)1-6-(С3- ...

ПРОИЗВОДНЫЕ УРАЦИЛА ИЛИ ТИМИНА ДЛЯ ЛЕЧЕНИЯ ГЕПАТИТА С

... 1. Соединение или его соль, где ! это соединение соответствует по структуре формуле I: ! ; ! выбрана из группы, состоящей из одинарной углерод-углеродной связи и двойной углерод-углеродной связи; ! R1 выбран из группы, состоящей из водорода, метила и азотзащищающей группы; ! R2 выбран из группы, состоящей из водорода, гало, гидрокси, метила, циклопропила и циклобутила; ! R3 выбран из группы, состоящей из водорода, гало, оксо и метила; ! R4 выбран из группы, состоящей из гало, алкила, алкенила, алкинила, нитро, циано, азидо, алкилокси, алкенилокси, алкинилокси, амино, аминокарбонила, аминосульфонила, алкилсульфонила, карбоциклила и гетероциклила, где ! (a) амино, аминокарбонил, и аминосульфонил необязательно замещены: ! (1) одним или двумя заместителями, независимо выбранными из группы, состоящей из алкила, алкенила, алкинила и алкилсульфонила, или ! (2) двумя заместителями, которые вместе с аминоазотом образуют однокольцевой гетероцикл, и ! (b) алкил, алкенил, алкинил, алкилокси, алкенилокси ...

Glukopyranosid-Benzothiophene

DIPHENYLAETHYLEN-DERIVATE.

VERFAHREN ZUR HERSTELLUNG VON 6-ARYL-2-METHYL-PYRIDINEN.

8-(BIARYL)CHINOLIN-PDE4-INHIBITOREN

BENZIMIDAZOLVERBINDUNGEN UND IHRE VERWENDUNG ALS GABA A RECEPTOR KOMPLEX MODULATOREN

ORGANISCHE ELEKTROLUMINESZIERENDE VERBINDUNG UND DIESE UMFASSENDE ORGANISCHE ELEKTROLUMINESZIERENDE VORRICHTUNG

Die vorliegende Offenbarung betrifft eine organische elektrolumineszierende Verbindung und eine diese umfassende organische elektrolumineszierende Vorrichtung. Durch Einbeziehung der organischen elektrolumineszierenden Verbindung gemäß der vorliegenden Offenbarung kann eine organische elektrolumineszierende Vorrichtung mit niedriger Treiberspannung und/oder hoher Lichteffizienz und/oder langer Lebensdauer bereitgestellt werden.

MATERIALIEN AUF BASIS VON TRIPHENYLEN FÜR ORGANISCHE ELEKTROLUMINESZENZVORRICHTUNGEN

Glutarimide.

HYDROXAMSÄURE-DERIVATE ALS MATRIX METALLOPROTEINASEINHIBITOREN

EP4 Rezeptor selektive Agonisten zur Behandlung der Osteoporose

PYRROL- UND PYRAZOLDERIVATE ALS POTENTIATOREN VON GLUTAMATREZEPTOREN

Compound Libraries

C-Glycosides and preparation thereof as antidiabetic agents

Pyrimidine Compounds

The synthesis of novel compound (I) is described: 5-bromo-2-iodopyrimidine may be used for the synthesis of a range of chemical compounds both known and novel. The synthesis of a number of novel liquid crystalline compounds is described.

Red colouring hyperchromic 3 H-Naphtho[2,1-b]Pyrans

Red colouring hyperchromic compounds having general formula (I), where R1 is H, NR2R3, OR4, SR4 or R7 wherein R2 and R3 are alkyl or carbocyclic groups or together with the nitrogen to which they are attached form a heterocyclic ring; R4 is the same as R1 or is alkyl, perhaloallyl, aryl or heteroaryl; R7 is alkyl, haloalkyl, alkylthio, aryl, arylthio, heteroaryl, halogen, nitrile, carboxylate, ester, nitro, or a carbocyclic or heterocyclic ring fused to faces f, gh, i, j or k; and R5 is a cyclic aminoaryl group, an indolinoaryl group, a tricyclic nitrogen heterocycle, or an unsaturated cyclic aminoaryl group.

UREA AND THIOUREA DERIVATIVES AND PROCESS FOR THEIR PREPARATION

DERIVATIVES OF 4-HYDROXYCOUMARIN AND RODENTICIDAL COMPOSITIONS THEREOF

OXIRANE COMPOUNDS

Chemical compounds

Novel herbicides

Dihydroxy aromatic heterocyclic compound

1-Arylcarbonyl-4-oxy-piperidine compounds useful for the treatment of neurodegenerative diseases

Novel benzyl(idene)-lactam derivatives

Benzodioxane inhibitors of leukotriene production

Bicyclo 2,3-benzodiazepines and spirocyclically substituted 2,3-benzodiazepines

2,3-substituted indole compounds as anti-inflammatory and analgesic agents

Antibacterial quinoline derivatives

Matrix metallproteinase inhibitors

Substituted chroman compounds as calcium sensing receptor modulators

Ep4 receptor selective agonists in the treatment of osteoporosis.

Antiviral drugs for treatment of arenavirus infection

Dihydrofuran derivatives as insecticidal compounds

Non-peptidyl inhibitors of vla-4 dependent cell binding useful in treating inflammatory autoimmune and respiratory diseases

2,3-Substituted indole compounds as anti-inflammatory and analgesic agents.

This invention provides a compound of the following formula: Z or the pharmaceutically acceptable salts thereof wherein Z is OH, C\^ alkoxy, -NR"RJ or heterocycle; Q is selected from the following: (a) an optionally substituted phenyl, (b) an optionally substituted 6-membered monocyciic aromatic group containing one, two, three or four nitrogen atoMs). (c) an optionally substituted 5-membered monocyciic aromatic group containing one heteroatom selected from O, S and N and optionally containing one. two or three nitrogen atom(s) in addition to said heteroatom, (d) an optionally substituted C3.7 cycloalkyl and (e) an optionally substituted benzo-fuzed heterocycle; R1 is hydrogen. CM alkyl or halo; R: and RJ are independently hydrogen, OH, CM alkoxy. CM alkyl or CM aikyl substituted with halo, OH, CM alkoxy or CN; X is independently selected from H, halo, CM aikyl, halo-substituted C,. 4 alkyl, OH, CM alkoxy, halo-substiruted CM alkoxy, CM alkylthio, NO;, NH2, di-(Ci. 4 alkyl)amino and CN; ...

Ep4 receptor selective agonists in the treatment of osteoporosis

"Benzofuran derivatives and their use in the treatment of migraine".

This invention relates to benzofuran derivatives, to processes for their ...

Hydroxamic acid derivatives as matrix metalloprotease (MMP) inhibitors.

Compounds of formula (I): or pharmaceutically or veterinarily acceptable salts thereof, or pharmaceutically or veterinarily acceptable solvates of either entity, wherein the broken line represents an optional bond; A is C or CH; B is CH2, O or absent; R1 and R2 are each independently selected from hydrogen, C, to C6 alkyl optionally substituted with C, to C4 alkoxy or phenyl, and C, to C6 alkenyl; or, together with the carbon atom to which they are attached, form a C3 to C6 cycloalkyl group which optionally incorporates a heteroatom linkage selected from O, SO, SO2 and NR6 or which is optionally benzo-fused; R3 is hydrogen, halo, R7 or OR7; R4 is hydrogen, Cn to C4 alkyl, C, to C4 alkoxy, trifiuoromethyl or halo; R8 is hydrogen or C, to C4 alkyl; R7 is an optionally substituted monocyclic or bicyclic ring system; m is 1 or 2; and n is 0, 1 or 2; with the provison that B is not O when A is C; are MMP inhibitors useful in the treatment of, inter alia, tissue ' ulceration, wound repair and ...

4-phenylpyrane-3,5-diones,4-phenylthiopyrane-3,5-diones and 2-phenylcyclohexane-1,3,5-triones as herbicides

Dihydroxy aromatic heterocyclic compound

Matrix metalloproteinase inhibitors

Non-pepdyl inhibitors of VLA-4 dependent cell binding useful in treating inflammatory, autoimmune, and respiratory diseases.

Compounds of Formula (1.0.0): are described wherein A is for example aryl, heteroaryl or heterocyclyl, Y is preferably -C(=O)-; B is independently selected from a group of moieties, the most preferred of which are those of partial Formulas (1.1.2) and (1.1.6): and E is a single bond; oxygen; 1,1-cyclopropyl; C(CH3)2; CF2; or a bridging moiety of partial |y Formula (1.9.0):5 where R1a is hydrogen when R1 has the meaning of a mono-valent substituent; and R1a is a single bond when R1 has the meaning of a di-valent substituent. Said compounds are useful in methods of treating or preventing an inflammatory, autoimmune or respiratory diseases by inhibiting cell adhesion and consequent or associated pathogenic processes subsequently mediated by VLA-4.

Antibacterial quinoline derivatives

Benzodioxane inhibitors of leukotriene production

Hydroxyamic acid derivatives as matrix metalloprotease (mmp)

Sulfonylbenzene compounds as anti-inflammatory/analgesic agents.

This invention provides a compound of the formula or its pharmaceutically acceptable salt thereof, wherein a is partially unsaturated or unsaturated five membered heterocyclic, or partially unsaturated or unsaturated five membered carbocyclic, wherein the 4-(sulfonyl)phenyl and the 4-substituted phenyl in the formula (i)are attached to ring atoms of ring a, which are adjacent to each other; r1 is optionally substituted aryl or heteroaryl, with the proviso that when a is pyrazole, r1 is heteroaryl; r2 is c1-4 alkyl, halo-substituted c1-4 alkyl, c1-4 alkylamino, c1-4 dialkylamino or amino; r3, r4 and r5 are independently hydrogen, halo, c1-4 alkyl, halo substituted c1-4 alkyl or the like; ot two of r3, r4 and r5 are taken together with atoms to which they are attached and form a 4-7 membered ring; r6 and r7 are independently hydrogen, halo, c1-4 alkyl, halo-substituted c1-4 alkyl, c1-4 alkoxy, c1-4 alkylthio, c1-4 alkylamino or n,n-di c1-4 alkylamino; and m and n are independently 1, 2, 3 ...

EP4 receptor selective agonists in the treatment of osteoporosis.

This invention is directed to EP4 receptor selective prostaglandin agonists of the Formula I, wherein R2, X, Z and Q are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds. This invention also directed to methods of treating conditions which present with low bone mass, particularly osteoporosis, frailty, an osteoporotic fracture, a bone defect, childhood idiopathic bone loss, alveolar bone loss, mandibular bone loss, bone fracture, osteotomy, bone loss associated with periodontitis, or prosthetic ingrowth in a mammal comprising administering those compounds.

Inhibitors of human immunodeficiency virus replication

2,3-substituted indole compounds as anti-inflammatory and analgesic agents

BENZOFURAN DERIVATIVES PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR MEDICAL USE

Non-peptidyl inhibitors of vla-4 dependent cell binding useful in treating inflammatory autoimmune and respiratory diseases

Insecticidal n-(substituted phenyl) methyl) piperidines

Compounds of the following structure,the corresponding n-oxides and agriculturally acceptable salts, are disclosed as effective insecticides:.....In which q is selected from hydrogen,hydroxy, and fluorine; r is selected from a heteroaryl having5 or 6 ring atoms, and .....In which v is hydrogen,halogen.ALkyl,haloalkyl,or alkoxy; w and x are independently selected from a wide variety of substituents, y and z are independently selected form hydrogen and alkoxy; w and x are taken together may be -och2ch2o-,-ch2c[ch3]20-,or -oc[ch3]20-;r1 and r2 are independently selected from phenyl substituted with halogen,alkyl, haloakyl, haloalkoxy, alkysulfonyloxy, and haloalkysulfonyloxy; and n is 1,2,or 3;with the proviso that each aliphatic moiety contains not more than 6 carbon atoms, halogen means chlorine ofr fluorine, and each alkyl substituent on an amino nitrogen contains 1 to 3 carbon atoms. The manner of preparing these compounds is also disclosed.

EP4 Receptor selective agonists in the treatment of osteoporosis.

The invention is directed to methods of treating conditions which present with low bone mass, particularly osteoporosis, frailty, an osteoporotic fracture, a bone defect, childhood idiopathic bone loss, alveolar bone loss, mandibular bone loss, bone fracture, osteotomy, bone loss associated with periodontitis, or prosthetic ingrowth comprising administering prostaglandin agonists which are EP4 receptor selective prostaglandin agonists. This invention is especially directed to those methods wherein the EP4 receptor selective agonist is a compound of Formula (I) wherein the variables are as defined in the specification.

4-phenyl-pyrane-3,5-diones, 4-phenyl-thiopyrane-3,5-diones and cyclohexanetriones as novel herbicides

Novel benzyl(idene)-lactam derivatives

Matrix metallproteinase inhibitors

ANTIVIRAL DRUGS FOR TREATMENT OF ARENAVIRUS INFECTION

1-Arylcarbonyl-4-oxy-piperidine compounds useful for the treatment of neurodegenerative diseases

Bicyclo 2,3-benzodiazepines and spirocyclically substituted 2,3-benzodiazepines

Indole and indazole compounds that activate AMPK

Antibacterial quinoline derivatives

Substituted chroman compounds as calcium sensing receptor modulators

Antiviral drugs for treatment of arenavirus infection

Novel c-aryl glucoside sglt2 inhibitors and pharmaceutical compositions comprising same

A novel C-aryl glucoside compound, or a pharmaceutically acceptable salt or a prodrug thereof having an inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) being present in the intestine and kidney; and a pharmaceutical composition comprising the same as an active ingredient, which is useful for preventing or treating metabolic disorders, particularly, diabetes, are provided.

Light-emitting device material and light-emitting device

Embodiments provide a light emitting device material characterized by containing an anthracene compound represented by the following general formula. where R 19 to R 37 are a hydrogen atom, alkyl group, cycloalkyl group, heterocyclic group or the like; n is 1 or 2; and A is a heteroarylene group or arylene group. Any one of the R 19 to R 27 and any one of the R 28 to R 37 are used for linking with A. The present teachings allow a light emitting device having high luminous efficiency and excellent durability.

Glycoside derivatives and uses thereof

This invention relates to compounds represented by formula (I): wherein the variables are defined as herein above, which are useful for treating diseases and conditions mediated by the sodium D-glucose co-transporter (SGLT), e.g. diabetes. The invention also provides methods of treating such diseases and conditions, and compositions etc. for their treatment.

Compounds for the treatment of hepatitis c

The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

4-(Substituted Anilino)-Quinazoline Derivatives Useful as Tyrosine Kinase Inhibitors

The present invention relates to 4-(substituted anilino)-quinazoline derivatives as tyrosine kinase inhibitors. Specifically, compounds of formula I, or pharmaceutically acceptable salts or solvates thereof are disclosed, in which each substitutent in formula I is defined in the description. Preparation method of the compounds of formula I, pharmaceutical compositions and pharmaceutical uses thereof are also disclosed. The compounds of formula I are effective tyrosine kinase inhibitors.

Glycoside derivatives and uses thereof

The present invention provides a compound of formula I; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Novel benzofurane-piperidine compounds

The present invention is concerned with novel selective dual modulators of the 5-HT 2A and D 3 receptors of formula (I) wherein R 1 , R 2 , R 3 , n, and Y are as described herein, as well as pharmaceutically acceptable salts and esters thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as pharmaceuticals.

Inhibitors of bruton's tyrosine kinase

This application discloses compounds according to generic Formula I: wherein all variables are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formula I and at least one carrier, diluent or excipient.

Biarylamide inhibitors of leukotriene production

The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, C, R 1a , R 1b , R 2 , R 3 , R 4a and R 4b are as defined herein. The invention also relates to pharmaceutical compositions comprising 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.

Inhibitors of hepatitis c virus ns5b polymerase

Disclosed are compounds of formula (I) that are used as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Glycoside derivatives and uses thereof

The present invention provides a compound of formula I; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Pyrrolidine or thiazolidine carboxylic acid derivatives, pharmaceutical composition and methods for use in treating metabolic disorders as agonists of g-protein coupled receptor 43 (gpr43)

The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases.

PROLYL HYDROXYLASE INHIBITORS

The invention described herein relates to certain pyrimidinetrione N-substituted glycine derivatives of formula (I) 2. The method according to wherein:X is O;Y is O;{'sup': 1', '4, 'sub': 1-', '10', '2-', '10', '2-', '10', '3', '8', '3', '8', '1-', '10', '5', '8', '5', '8', '1-', '10', '3', '8', '3', '8', '1-', '10', '1-', '10', '1-', '10, 'Rand Rare each independently selected from the group consisting of hydrogen, CCalkyl, CCalkenyl, CCalkynyl, C-Ccycloalkyl, C-Ccycloalkyl-CCalkyl, C-Ccycloalkenyl, C-Ccycloalkenyl-CCalkyl, C-Cheterocycloalkyl, C-Cheterocycloalkyl-CCalkyl, aryl, aryl-CCalkyl, heteroaryl and heteroaryl-CCalkyl;'}{'sup': 2', '7', '8', '9, 'Ris —NRRor —OR;'}{'sup': '3', 'sub': 1-', '4, 'claim-text': [{'sup': 7', '8, 'sub': 1-', '10', '2-', '10', '2-', '10', '3', '8', '3', '8, 'where Rand Rare each independently selected from the group consisting of hydrogen, CCalkyl, CCalkenyl, CCalkynyl, C-Ccycloalkyl, C-Cheterocycloalkyl, aryl and heteroaryl, and'}, {'sup': '9', 'sub': 1-', '10', '3', '6, 'Ris H or a cation, or CCalkyl which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of C-Ccycloalkyl, heterocycloalkyl, aryl and heteroaryl,'}, {'sup': 1', '2', '3', '4', '7', '8', '9', '10', '5', '6', '10', '10', '10', '10', '10', '5', '6', '5', '6', '5', '10', '5', '10', '5', '6', '5', '5', '6', '5', '6', '5', '10', '5', '6', '10, 'sub': 1', '6', '1', '6', '2', '2', '2', '2', '10', '2', '10', '3', '6', '3', '6', '1', '6', '1', '6', '1-', '10', '2-', '10', '2-', '10', '1', '4', '3', '6', '3', '6', '2', '1', '4', '3', '8', '3', '8', '6', '14', '1-', '10', '1-', '10, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'where any carbon or heteroatom of R, R, R, R, R, R, Ris unsubstituted or is substituted with one or more substituents independently selected from C-Calkyl, C-Chaloalkyl, halogen, —OR, —NRR, oxo, cyano, nitro, —C(O)R, —C(O)OR, —SR, —S(O)R, —S(O)R, —NRR, —CONRR, —N(R)C(O)R, —N(R)C(O)OR, —OC(O) ...

PHARMACEUTICALLY ACTIVE DISUBSTITUTED TRIAZINE DERIVATIVES

The present invention relates to disubstituted triazine derivatives and/or pharmaceutically acceptable salts thereof, the use of these derivatives as pharmaceutically active agents, especially for the prophylaxis and/or treatment of infectious diseases, including opportunistic diseases, immunological diseases, autoimmune diseases, cardiovascular diseases, cell proliferative diseases, inflammation, erectile dysfunction and stroke, and pharmaceutical compositions containing at least one of said disubstituted triazine derivatives and/or pharmaceutically acceptable salts thereof. Furthermore, the present invention relates to the use of said disubstituted triazine derivatives as inhibitors for a protein kinase. 6. The compound according to claim 1 , wherein the compound is selected from the group of compounds consisting of:3-[(4-(2-Methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethanesulfonamide,3-[(4-(4-Fluoro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(5-Fluoro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(6-Fluoro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(3,5-Difluoro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(4-Chloro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(5-Chloro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(2-Methoxy-4-trifluoromethyl-phenyl)-1,3,5-triazin-2-yl)amino]benzene-methanesulfonamide,3-[(4-(2-Methoxy-5-trifluoromethyl-phenyl)-1,3,5-triazin-2-yl)amino]benzene-methanesulfonamide,3-[(4-(5-Hydroxymethyl-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzene-methanesulfonamide,3-[(4-(5-Formyl-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(2-Ethoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethanesulfonamide,3-[(4-(2-Benzyloxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethanesulfonamide,1-(3-{[4-(2-phenoxyphenyl)-1,3,5-triazin-2-yl]amino}phenyl) ...

Use of 1H-quinazoline-2,4-diones

The invention concerns the use of competitive AMPA receptor antagonists for the treatment or prevention of photosensitive epilepsy. 4. A compound of formula (I) for use according claim 1 , selected from the group consisting of:N-[6-(1-Hydroxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Methoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Hydroxy-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Isopropoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Ethoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[2,4-Dioxo-6-(1-propoxy-propyl)-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1 -isopropoxy-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[7-Difluoromethyl-6-(1-ethoxy-ethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[2,4-Dioxo-6-(1-propoxy-ethyl)-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Butoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Isobutoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-methoxy-butyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Ethoxy-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Cyclopentyloxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Hydroxy-butyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Methoxy-2-methyl-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(3-Hydroxy-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1- ...

2-(substituted phenyl)-6-amino-5-alkoxy, thioalkoxy and aminoalkyl-4-pyrimidinecarboxylates and their use as herbicides

2-(Substituted phenyl)-6-amino-5-alkoxy, thioalkoxy and aminoalkyl-4-pyrimidinecarboxylic acid and its derivatives are potent herbicides demonstrating broad spectrum of weed control.

Use of 1H-quinazoline-2,4-diones

The invention concerns the use of competitive AMPA receptor antagonists for the treatment, prevention or delay of progression of spasticity. 4. A compound of formula (I) according to claim 1 , selected from the group consisting of:N-[6-(1-Hydroxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Methoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Hydroxy-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Isopropoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Ethoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-Dioxo-6-(1-propoxy-propyl)-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-isopropoxy-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[7-Difluoromethyl-6-(1-ethoxy-ethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[2,4-Dioxo-6-(1-propoxy-ethyl)-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Butoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Isobutoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-methoxy-butyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Ethoxy-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Cyclopentyloxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Hydroxy-butyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1-Methoxy-2-methyl-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(3-Hydroxy-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide;N-[6-(1- ...

6-ACYL-1,2,4-TRIAZINE-3,5-DIONE DERIVATIVE AND HERBICIDES

Disclosed are compounds exhibiting sufficient herbicidal activity at low application dosage when they are applied to soils and foliage, and an agrochemical composition using the same, in particular herbicides. The compounds are triazine derivatives represented by following Formula 1 or salts thereof, and the herbicides containing them: [Chem. 28] wherein in the formula, Rrepresents a hydrogen atom; a C-Calkyl group; a C-Calkenyl group, etc., Rrepresents a C-Calkyl group, etc., Y and Z represent an oxygen atom or a sulfur atom, and A represents a 5- or 6-membered cyclic group which may contain a nitrogen atom, an oxygen atom, or a sulfur atom. 2. The triazine derivative or the salt thereof according to claim 1 , wherein{'sup': 1', '31', '32, 'sub': 1', '12', '2', '6', '2', '6', '3', '6', '3', '6', '3', '6', '1', '6', '1', '6', '2', '6', '2', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '6', '2', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Rrepresents a C-Calkyl group; a C-Calkenyl group; a C-Calkynyl group; a C-Ccycloalkyl group; a C-Ccycloalkenyl group; a C-Ccycloalkyl C-Calkyl group; a C-Chaloalkyl group; a C-Chaloalkenyl group; a C-Chaloalkynyl group; a C-Chalocycloalkyl group; a C-Calkylthio C-Calkyl group; a C-Calkylsulfinyl C-Calkyl group; a C-Calkylsulfonyl C-Calkyl group; a C-Calkoxy C-Calkyl group; a C-Calkoxy C-Calkoxy C-Calkyl group; a C-Ccycloalkyloxy C-Calkyl group; a phenyloxy C-Calkyl group (the phenyl in the group may be substituted with 1 to 5 identical or different substituents selected from the Substituent group α); a phenylthio C-Calkyl group (the phenyl in the group may be substituted with 1 to 5 identical or different substituents selected from the Substituent group α); a phenylsulfinyl C-Calkyl group (the phenyl in the ...

ANTIMICROBIAL AGENTS

The invention provides a compound of formula I:or a salt thereof, wherein R-Rand X and Y have any of the values described in the specification, as well as compositions comprising a compound of formula I. The compounds are useful as antibacterial agents. 2. The compound of wherein:{'sup': 1', 'y', 'y, 'sub': 1', '6, 'Ris Ror (C-C)alkyl that is substituted with one or more R;'}{'sup': 2', 'z', 'x, 'sub': 1', '6, 'Ris Ror (C-C)alkyl that is substituted with one or more R;'}{'sup': 4', '5', '6', '7', 'd', '4', '5', '6', '7', 'p', 'p', 'p', 'g', 'h', 'g', 'h', 'a', '4', '5', '6', '7', 'b, 'sub': 1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '3', '2', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'at least one of RRRand Ris aryl or heteroaryl wherein each aryl or heteroaryl is optionally substituted with one or more (e.g. 1, 2, 3, or 4) R; and the remainder of RRRand Rare each independently H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl, trifluoromethoxy, (C-C)alkyl, (C-C)cycloalkyl, (C-C)alkoxy, (C-C)alkoxycarbonyl, (C-C)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, (C-C)alkylthio, —S(O)R, —S(O)R, —S(O)R, —S(O)NRR, and —NRR; wherein any alkyl and any alkyl or alkanoyl portion of any aryl(C-C)alkyl, heteroaryl(C-C)alkyl, aryl(C-C)alkanoyl or heteroaryl(C-C)alkanoyl is optionally substituted with one or more (e.g. 1, 2, 3, or 4) R; and wherein any aryl, heteroaryl, or any aryl or heteroaryl portion of any aryl(C-C)alkyl, heteroaryl(C-C)alkyl, aryl(C-C)alkanoyl or heteroaryl(C-C)alkanoyl of RRRand Ris optionally substituted with one or more (e.g. 1, 2, 3, or 4) R;'}{'sup': 8', 'p', 'p', 'p', 'g', 'h', 'g', 'h', '8', 'a', '8', 'b, 'sub': 1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '3', '2, 'Ris H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl, trifluoromethoxy, (C-C)alkyl, (C-C)cycloalkyl, (C-C)alkoxy, (C-C)alkoxycarbonyl, (C-C)alkanoyloxy, aryl, heteroaryl, aryloxy, ...

3-aminopyrrolidine derivatives as modulators of chemokine receptors

The present invention relates to 3-aminopyrrolidine derivatives of the formula I: (wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, Y and X are as defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of chemokine receptors and more specifically as a modulator of the CCR2 and/or CCR5 receptor. The compounds and compositions of the invention may bind to chemokine receptors, e.g., the CCR2 and/or CCR5 chemokine receptors, and are useful for treating diseases associated with chemokine, e.g., CCR2 and/or CCR5, activity, such as atherosclerosis, restenosis, lupus, organ transplant rejection and rheumatoid arthritis.

IRE-1alpha INHIBITORS

Compounds which directly inhibit IRE-1α activity in vitro, prodrugs, and pharmaceutically acceptable salts there-of. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response or with regulated IRE1-dependent decay (RIDD) and can be used as single agents or in combination therapies. 114-. (canceled)16. A product comprising a compound of , wherein the product is selected from the group consisting of (a) a pharmaceutical composition comprising the compound of and a pharmaceutically acceptable vehicle; and (b) a complex comprising IRE-1α and the compound of .17. A method of inhibiting IRE-1α activity claim 15 , comprising contacting IRE-1α with a compound of or a prodrug or pharmaceutically acceptable salt thereof.18. The method of wherein the IRE-1α activity is selected from the group consisting of cleavage of RNA claim 17 , cleavage of mRNA claim 17 , RNA splicing claim 17 , and mRNA splicing.19. The method of wherein the IRE-1α activity is cleavage of mRNA and wherein the mRNA is selected from the group consisting of Blos1 mRNA claim 18 , DGAT2 mRNA claim 18 , CD59 mRNA claim 18 , and IRE-1α mRNA.20. The method of claim 18 , wherein the IRE-1α activity is inhibited to treat a disorder associated with the unfolded protein response claim 18 , comprising administering to a patient in need thereof the compound of or the prodrug or pharmaceutically acceptable salt thereof.21. The method of further comprising administering a therapeutic agent that induces or up-regulates IRE-1α expression.2202. The method of claim further comprising administering a therapeutic agent which is less effective when IRE-1α is expressed.23. The method of claim 20 , further comprising administering to the patient a proteasome inhibitor.24. The method of claim 20 , wherein the IRE-1α activity is inhibited to treat a disorder associated with a target of regulated IRE 1-dependent decay (RIDD) claim 20 , comprising administering to a patient in need ...

2-Thiopyrimidinones

Myeloperoxidase inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, cardiovascular conditions. 111.-. (canceled)12. The compound 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3 ,4-dihydropyrimidin-1(2H)-yl)acetamide or a pharmaceutically acceptable salt thereof.13. (canceled)15. A method of treating cardiovascular conditions comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of or a prodrug thereof or a pharmaceutically acceptable salt of said compound or of said prodrug.16. A method as recited in wherein the cardiovascular condition is heart failure claim 15 , congestive heart failure claim 15 , peripheral arterial disease claim 15 , pulmonary hypertension or vasculitis.17. A method as recited in wherein the mammal has unstable angina or has experienced myocardial infarction.18. A pharmaceutical composition which comprises a therapeutically effective amount of a compound of or a prodrug thereof or a pharmaceutically acceptable salt of said compound or of said prodrug and a pharmaceutically acceptable carrier claim 12 , vehicle or diluent.19. A pharmaceutical combination composition comprising: a therapeutically effective amount of a composition comprising:{'claim-ref': {'@idref': 'CLM-00012', 'claim 12'}, 'a first compound, said first compound being a compound of , a prodrug thereof, or a pharmaceutically acceptable salt of said compound or of said prodrug;'}a second compound, said second compound being an angiotensin converting enzyme inhibitor, a HMG-CoA reductase inhibitor, a non-steroidal anti-inflammatory agent, a Factor Xa inhibitor or warfarin; anda pharmaceutical carrier, vehicle or diluents.2029.-. (canceled) This nonprovisional application claims priority from U.S. Provisional Application No. 61/558,605, filed on Nov. 11, 2011.This invention relates to compounds that are myeloperoxidase inhibitors, pharmaceutical compositions ...

Quinoxalinone derivatives as insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes

The present invention relates to quinoxalinone derivatives of formula (I), wherein R1, R2, R3, R4, R5 and R6 are as defined in claim as insulin secretion stimulators. The invention also relates to the preparation and use of these quinoxalinone derivatives for the prophylaxis and/or treatment of diabetes and pathologies associated. 124.-. (canceled)26. A method according to claim 25 , wherein the compound induces insulin secretion in response to glucose concentration.27. A method according to claim 25 , for the treatment of diabetes.28. A method according to claim 27 , for the treatment of type II diabetes.29. A method according to claim 25 , for the treatment of dyslipidaemia or obesity30. A method according to claim 25 , for the treatment of diabetes related microvascular or macrovascular complications.31. A method according to claim 30 , wherein the complications include arterial hypertension claim 30 , atherosclerosis claim 30 , inflammatory processes claim 30 , microangiopathy claim 30 , macroangiopathy claim 30 , retinopathy or neuropathy.32. A method according to claim 25 , for the reducing hyperglycaemia.33. A method according to claim 25 , wherein R1 is: alkyl claim 25 , cycloalkyl claim 25 , cycloalkylalkyl claim 25 , heterocycloalkyl claim 25 , heterocycloalkylalkyl claim 25 , alkyloxyalkyl claim 25 , R7R8N-alkyl or alkylthioalkyl; wherein the heterocycloalkyl groups have one or more heteroatom selected from N claim 25 , O and S; and wherein each of these groups is optionally substituted by one or more groups selected from Y or Z.34. A method according to claim 25 , wherein R1 is: methyl claim 25 , ethyl claim 25 , butyl claim 25 , cyclopropyl or cyclopropylmethyl; wherein each of these groups is optionally substituted by one or more groups selected from Y or Z.35. A method according to claim 25 , wherein R1 is: 2 claim 25 ,2-difluoroethyl or 2 claim 25 ,2 claim 25 ,2-trifluoroethyl.36. A method according to claim 25 , wherein R6 is: alkyl claim 25 , aryl ...

Novel triazinedione derivatives as gabab receptor modulators

The present invention provides novel compounds of formula I wherein W 1 , W 2 , W 3 , W 4 , W 5 , B, X 1 , X 2 , X 3 , X 4 , X 5 , E and L are as defined herein; invention compounds are gamma amino butyrique acid receptor-subtype B (“GABA B ”) positive allosteric modulators (enhancers), which are useful to provide methods of treating or preventing diseases or disorders, including treatment of anxiety, depression, epilepsy, schizophrenia, cognitive disorders, spasticity and skeletal muscle rigidity, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, cerebral palsy, neuropathic pain and craving associated with cocaine and nicotine, panic disorder, posttraumatic stress disorders, urge urinary incontinence, gastroesophageal reflux disease, transient lower oesophageal sphincter relaxations, functional gastrointestinal disorders and irritable bowel syndrome.

POLYMORPHIC FORMS OF LAPATINIB DITOSYLATE AND PROCESSES FOR THEIR PREPARATION

There is provided a crystalline form of Lapatinib, termed APO-I, and methods for making APO-I. There is also provided a crystalline solvate form of Lapatinib, termed APO-II, and methods for making APO-II. 1. APO-I polymorphic form of Lapatinib ditosylate.2. The APO-I polymorphic form of Lapatinib ditosylate of having a powder X-ray diffraction pattern comprising peaks claim 1 , in terms of degrees 2-theta claim 1 , at approximately 4.6 claim 1 , 18.8 claim 1 , 19.5 claim 1 , 21.3 claim 1 , 22.0 and 23.0.3. The APO-I polymorphic form of Lapatinib ditosylate of wherein the powder X-ray diffraction pattern further comprising peaks claim 2 , in terms of degrees 2-theta claim 2 , at approximately 8.3 claim 2 , 9.3 claim 2 , 11.8 claim 2 , 13.8 claim 2 , 14.9 claim 2 , 16.8 claim 2 , 17.3 claim 2 , 25.2 and 26.2.4. The APO-I polymorphic form of Lapatinib ditosylate of having a DSC thermogram comprising two endothermic peaks with peak onset temperatures of approximately 169.5° C. and 247.9° C. and peak maximums of approximately 179.5° C. and 250.5° C.5. The APO-I polymorphic form of Lapatinib ditosylate of having a PXRD diffractogram substantially similar to a PXRD diffractogram as depicted in .6. The APO-I polymorphic form of Lapatinib ditosylate of having a DSC thermogram substantially similar to a DSC thermogram as depicted in .7. APO-II polymorphic form of Lapatinib ditosylate.8. The APO-II polymorphic form of Lapatinib ditosylate of having a powder X-ray diffraction pattern comprising peaks claim 7 , in terms of degrees 2-theta claim 7 , at approximately 4.4 claim 7 , 8.3 claim 7 , 13.1 claim 7 , 19.3 claim 7 , 20.9 and 21.4.9. The APO-II polymorphic form of Lapatinib ditosylate of wherein the powder X-ray diffraction pattern further comprising peaks claim 8 , in terms of degrees 2-theta claim 8 , at approximately 9.6 claim 8 , 10.5 claim 8 , 14.0 claim 8 , 15.0 16.9 claim 8 , 18.2 claim 8 , 25.3 claim 8 , and 26.6.10. The APO-II polymorphic form of Lapatinib ...

BICYCLO-SUBSTITUTED PYRAZOLON AZO DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF

The bicyclo-substituted pyrazolon-azo derivatives of formula (I) or pharmaceutical acceptable salts, hydrates or solvates thereof, methods for their preparation, pharmaceutical compositions containing the same and their use as a therapeutic agent, especially as thrombopoietin (TPO) mimetics and their use as agonists of thrombopoietin receptor are disclosed. The definition of substituents in formula (I) are the same as defined in the description. 113-. (canceled)15. The compound according to claim 14 , wherein R claim 14 , R claim 14 , and Rare hydrogen.16. The compound according to claim 14 , wherein R claim 14 , R claim 14 , R claim 14 , and Rare each independently hydrogen claim 14 , methyl claim 14 , and ethyl. This disclosure relates to novel bicyclo-substituted pyrazolon-azo derivatives represented by formula (I), methods for their preparation, pharmaceutical compositions containing the same, and their use as a therapeutic agent, particularly as thrombopoietin (TPO) mimetics and their use as agonists of the thrombopoietin receptor.Thrombopoietin (TPO), also called megakaryocyte growth and development factor (MGDF), thrombocytopoiesis stimulating factor (TSF), c-myeloproliferative leukemia ligand (c-Mpl), mpl ligand, or megapoietin, is a glycoprotein that has been shown to be involved in the production of platelets. See Wendling, F., et. al., Biotherapy 10(4): 269-77 (1998); Kuter D. I. et al., The Oncologist, 1: 98-106 (1996); Metcalf, Nature 369: 519-520 (1994).Under certain circumstances, the activity of TPO results from the binding of TPO with the TPO receptor (also called MPL). The TPO receptor has been cloned and its amino acid sequence has been described. See Vigon et al., Proc. Nat. Acad. Sci., 89: 5640-5644 (1992).TPO is a 332-amino acid glycosylated polypeptide that plays a key role in the regulation of megakaryocytopoiesis, and in the process in which platelets are produced by bone marrow megakaryocytes. See Kuter et al., Proc. Natl. Acad. Sci. USA 91 ...

SUBSTITUTED ISOQUINOLINES AND THEIR USE AS TUBULIN POLYMERIZATION INHIBITORS

The present invention relates generally to substituted isoquinolines and their use as tubulin polymerization inhibitors. In particular, the invention relates to substituted isoquinolines which possess useful therapeutic activity, use of these compounds in methods of therapy and the manufacture of medicaments as well as compositions containing these compounds. 117.-. (canceled)19. The compound according to wherein:{'sup': '+', 'sub': 1', '6, 'X represents N or N—Z, wherein Z is selected in the group consisting of a (C-C)alkyl, an aryl and an acyl;'}{'sub': 1', '1', '5, 'claim-text': wherein Ra represents a NRa′Ra″ or ORa′″ group;', {'sub': 1', '5, 'wherein Ra′ and Ra″, independently from each other, are selected from the group consisting of H and (C-C)alkyl;'}, {'sub': 1', '5, 'wherein Ra′″ represents H or (C-C)alkyl;'}], 'Rrepresents H, CN, a CORa or a (C-C)alkyl;'}{'sub': 3', '2', '1', '5, 'claim-text': wherein Rb represents a NRb′Rb″ or ORb′″ group;', {'sub': 1', '5, 'wherein Rb′ and Rb′, independently from each other, are selected from the group consisting of H and (C-C)alkyl;'}, {'sub': 1', '5, 'wherein Rb′″ represents H or (C-C)alkyl;'}], 'Rrepresents H, CN, OH, a CORb, NHor a (C-C)alkyl;'}{'sub': 7', '1', '5', '1', '5', '1', '5', '1', '5', '1', '5, 'Rrepresents a (C-C)alkyl, a (C-C)alkoxy, a (C-C)alkylthio, a (C-C)alkylamino, a (C-C)dialkylamino;'}{'sub': 8', '1', '6', '2, 'claim-text': [{'sub': 1', '6', '2', '6', '2, 'wherein R and R′, independently from each other, are selected from the group consisting of H, a (C-C)alkyl, a (C-C)alkenyl, an acyl, an aryl, a heterocyclyl, amino acid, a Y—SOgroup, a P(O)(OG)(OG′) group,'}, {'sub': 1', '6', '2', '1', '6', '1', '6', '1', '6, 'wherein Y is selected in the group consisting of a hydrogen atom, (C-C)alkyl, NH, (C-C)alkylamino, di(C-C)alkylamino and (C-C)alkoxycarbonylamino;'}, {'sub': 1', '6, 'wherein G and G′, independently from each other, are selected in the group consisting of H, (C-C)alkyl and aryl;'}], ' ...

NOVEL TRPV3 MODULATORS

Disclosed herein are modulators of TRPV3 of formula (II): 2. The compound according to claim 1 , or a salt thereof claim 1 , wherein u is 0.3. The compound according to claim 2 , or a salt thereof claim 2 , wherein:{'sup': '1', 'Gis optionally substituted heteroaryl or optionally substituted cycloalkyl;'}{'sup': 2', '2d, 'Gis G; and'}{'sup': '2d', 'Gis optionally substituted aryl or optionally substituted heteroaryl.'}4. The compound according to claim 2 , or a salt thereof claim 2 , wherein:{'sup': '1', 'Gis optionally substituted pyridinyl, pyrimidinyl, thiazolyl, oxazolyl, or pyrazolyl;'}{'sup': 2', '2d, 'Gis G; and'}{'sup': '2d', 'Gis optionally substituted phenyl or optionally substituted pyridinyl.'}5. The compound according to claim 2 , or a salt thereof claim 2 , wherein:{'sup': 1', 'gc, 'sub': 1', '6', '1', '6', '2, 'Gis pyridinyl or pyrimidinyl; each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C-C-alkyl, C-C-haloalkyl, and N(R);'}{'sup': 'gc', 'sub': 1', '6, 'Ris hydrogen or C-C-alkyl;'}{'sup': 2', '2d, 'Gis G;'}{'sup': 2d', 'f, 'sub': 1', '6', '1', '6, 'Gis phenyl, pyridinyl, or pyrimidinyl; each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, —CN, C-C-alkyl, C-C-haloalkyl, and —OR; and'}{'sup': 'f', 'sub': 1', '6', '1', '6, 'Ris C-C-alkyl or C-C-haloalkyl.'}6. The compound according to claim 2 , or a salt thereof claim 2 , wherein:{'sup': 1', 'gc, 'sub': 1', '4', '1', '4', '2, 'Gis pyridinyl which is optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen, C-C-alkyl, C-C-haloalkyl, and N(R);'}{'sup': 'gc', 'sub': 1', '4, 'Ris hydrogen or C-C-alkyl;'}{'sup': 2', '2d, 'Gis G;'}{'sup': 2d', 'f, 'sub': 1', '4', '1', '4, 'Gis phenyl or pyridinyl; each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group ...

PYRIDAZINONES AND FURAN-CONTAINING COMPOUNDS

The present invention is directed to pyridazinone compounds of formula (I) and furan compounds of formula (II), pharmaceutical compositions of compounds of formula (I) and (II), kits containing these compounds, methods of syntheses, and a method of treatment of a proliferative disease in a subject by administration of a therapeutically effective amount of a compound of formulae (I) or (II). Both classes of compounds were identified through screening of a collection of small molecule libraries. 2. The compound according to claim 1 , wherein 4 claim 1 ,5-dichloro-2-m-tolyl-2H-pyridazin-3-one is specifically excluded.3. The compound according to claim 1 , wherein Rand Rare the same claim 1 , Ris hydrogen claim 1 , halo claim 1 , optionally substituted acyl claim 1 , optionally substituted heterocyclic claim 1 , optionally substituted aryl claim 1 , optionally substituted heteroaryl claim 1 , or optionally substituted hydroxy.4. The compound according to claim 3 , wherein Rand Rare both hydrogen.5. The compound according to claim 3 , wherein Rand Rare both chloro claim 3 , bromo claim 3 , iodo claim 3 , or fluoro.6. The compound according to claim 3 , wherein Rand Rare both optionally substituted hydroxy.7. The compound according to claim 3 , wherein Rand Rare both optionally substituted thio.8. The compound according to claim 3 , wherein Rand Rare both optionally substituted amino.9. The compound according to claim 3 , wherein Rand Rare both optionally substituted aliphatic.10. The compound according to claim 3 , wherein Rand Rare both optionally substituted heterocyclic.11. The compound according to claim 3 , wherein Rand Rare both cyano.12. The compound according to claim 1 , wherein Rand Rare the different claim 1 , Ris hydrogen claim 1 , halo claim 1 , optionally substituted acyl claim 1 , optionally substituted heterocyclic claim 1 , optionally substituted aryl claim 1 , optionally substituted heteroaryl claim 1 , or optionally substituted hydroxy.13. The compound ...

SALTS OF LAPATINIB

The present invention provides novel dioxalate salt of lapatinib, process for its preparation and pharmaceutical compositions comprising it. The present invention also provides novel monobesylate salt of lapatinib, process for its preparation and pharmaceutical compositions comprising it. The present invention further provides a process for the preparation of monohydrate form of lapatinib ditosylate. The present invention further provides a process for the preparation of anhydrous form of lapatinib ditosylate. 1. A dioxalate salt of lapatinib or monobesylate salt of lapatinib.2. A process for the preparation of lapatinib dioxalate , comprising:a. suspending lapatinib in an ether solvent to form a suspension;b. heating the suspension to an elevated temperature to form a solution;c. adding oxalic acid to the solution obtained in step (b); andd. isolating lapatinib dioxalate from the solution of step (c).3. The process according to claim 2 , wherein the ether solvent used in the process is selected from the group consisting of tetrahydrofuran claim 2 , 1 claim 2 ,4-dioxane claim 2 , tert-butyl methyl ether claim 2 , diethyl ether claim 2 , and mixtures thereof.4. The process according to claim 3 , wherein the ether solvent is tetrahydrofuran.5. The process according to claim 2 , wherein heating in step (b) is above 25° C.6. The process according to claim 5 , wherein heating is at 60 to 70° C.7. (canceled)8. A process for the preparation of lapatinib monobesylate claim 5 , comprising:a. dissolving lapatinib in a nitrile solvent to form a solution;b. heating the solution to an elevated temperature;c. adding benzenesulfonic acid to the solution obtained in step (b); andd. isolating lapatinib monobesylate from the solution from the solution of step (c).9. The process according to claim 8 , wherein the nitrile solvent used in the process is selected from the group consisting of acetonitrile claim 8 , propionitrile claim 8 , butyronitrile claim 8 , benzonitrile claim 8 , and ...

GPR120 RECEPTOR AGONISTS AND USES THEREOF

GPR120 agonists are provided. These compounds are useful for the treatment of metabolic diseases, including Type II diabetes and diseases associated with poor glycemic control. 125.-. (canceled)28. The compound of wherein Ris independently selected from the group consisting of F claim 27 , Cl claim 27 , —CH claim 27 , —CFand —OCH.29. The compound of claim 28 , wherein each Ris independently selected from the group consisting of F claim 28 , Cl claim 28 , —CH claim 28 , —CHand —CF.30. The compound of claim 29 , wherein Z is H or alkyl.31. The compound of claim 30 , wherein Z is H.32. The compound of claim 31 , wherein q is 2.33. The compound of claim 32 , wherein each of Rand Ris H. This application claims the benefit under 35 U.S.C. 119(e) of U.S. Provisional Application No. 61/138,923, filed Dec. 18, 2008, which is incorporated by reference in its entirety into this application.Diabetes mellitus can be divided into two clinical syndromes, Type I and Type II diabetes mellitus. Type I diabetes, or insulin-dependent diabetes mellitus, is a chronic autoimmune disease characterized by the extensive loss of beta cells in the pancreatic islets of Langerhans (hereinafter referred to as “pancreatic islet cells” or “islet cells”), which produce insulin. As these cells are progressively destroyed, the amount of secreted insulin decreases, eventually leading to hyperglycemia (abnormally high level of glucose in the blood) when the amount secreted drops below the level required for euglycemia (normal blood glucose level). Although the exact trigger for this immune response is not known, patients with Type I diabetes have high levels of antibodies against pancreatic beta cells (hereinafter “beta cells”). However, not all patients with high levels of these antibodies develop Type I diabetes.Type II diabetes, or non-insulin-dependent diabetes mellitus, develops when muscle, fat and liver cells fail to respond normally to insulin. This failure to respond (called insulin resistance) ...

POSITIVE ALLOSTERIC MODULATORS OF MGLUR2

The present invention is directed to benzimidazolone derivatives which are positive allosteric modulators of the mGluRreceptor, useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluRreceptor is involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved, such as schizophrenia. 2. The compound according to wherein Y is methyl.3. The compound according to wherein Ris selected from the group consisting of: cyclopropylmethyl claim 1 , 2 claim 1 ,2-difluorocyclopropylmethyl claim 1 , 2 claim 1 ,2-difluoro-1-methylcyclopropylmethyl claim 1 , 1-(trifluoromethyl)cyclopropylmethyl claim 1 , 4 claim 1 ,4 claim 1 ,4-trifluoro-2 claim 1 ,2-dimethylbutyl claim 1 , cyclobutylmethyl claim 1 , 2 claim 1 ,2-dimethylpropyl claim 1 , prop-2-enyl claim 1 , biphenyl and benzyl claim 1 , optionally substituted with methoxy or —OCF.5. The compound according to wherein Ris selected from the group consisting of halo claim 4 , —CN claim 4 , —N(O) claim 4 , amino claim 4 , —N(Calkyl) claim 4 , —C(O)—O—Calkyl claim 4 , —C(O)—Calkyl claim 4 , —S(O)—Calkyl claim 4 , Ccycloalkyl claim 4 , —C(Calkyl)-NHC(O)—O—Calkyl and Calkyl optionally substituted with 1 to 4 substituents independently selected from hydroxy and halo.7. The compound according to wherein Ris selected from the group consisting of: halo claim 6 , —CN claim 6 , —N(O) claim 6 , amino claim 6 , —N(Calkyl) claim 6 , —C(O)—O—Calkyl claim 6 , —C(O)—Calkyl claim 6 , —S(O)—Calkyl claim 6 , Ccycloalkyl and Calkyl optionally substituted with 1 to 4 substituents independently selected from hydroxy and halo.9. The compound according to wherein ring B is phenyl.10. The compound according to wherein ring B is pyridyl.11. The compound according to wherein Eis C and ...

NOVEL PEPERIDINE-FLAVAN ALKALOID COMPOUNDS DERIVED FROM AFRICAN HERB TEA KINKELIBA AS ANTI-DIABETIC AGENTS

This invention provides the methods of separation and identification of a novel type of piperidine flavan alkaloids from an African herbal tea, the leaves of commonly known as kinkeliba, and the procedures for preparing the total piperidine flavan alkaloids (TPFA). In particular, this invention relates to the use of the plant extract that may contain TPFA as anti-diabetic agents in treatment of metabolic disorders and other applications related to this new chemical structure and derivatives thereof. 2. The piperidine-flavan alkaloid compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rthrough Rare each hydrogen.3. The piperidine-flavan alkaloid compound of claim 1 , namely kinkéloid A claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sub': '1', 'Ris 2-piperidinyl;'}{'sub': 2', '3', '4', '5, 'R, R, R, and Rare each H; and'}{'sub': 6', '10, 'Rthrough Rare each hydrogen.'}4. The piperidine-flavan alkaloid compound of claim 1 , namely kinkéloid A claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sub': '2', 'Ris 2-piperidinyl;'}{'sub': 1', '3', '4', '5, 'R, R, R, Rare each H; and'}{'sub': 6', '10, 'Rthrough Rare each hydrogen.'}5. The piperidine-flavan alkaloid compound of claim 1 , namely kinkéloid B claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sub': '1', 'Ris 2-piperidinyl;'}{'sub': 2', '3', '5, 'R, R, and Rare each H;'}{'sub': '4', 'Ris OH;'}{'sub': 6', '10, 'Rthrough Rare each hydrogen.'}6. The piperidine-flavan alkaloid compound of claim 1 , namely kinkéloid B claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sub': '2', 'Ris 2-piperidinyl,'}{'sub': 1', '3', '5, 'R, R, and Rare each H;'}{'sub': '4', 'Ris OH;'}{'sub': 6', '10, 'Rthrough Rare each hydrogen.'}7. The piperidine-flavan alkaloid compound of claim 1 , namely kinkéloid C claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sub': '1', 'Ris 2- ...

Crystalline Pharmaceutical and Methods of Preparation and Use Thereof

Novel crystalline polymorphic forms, Forms A, B, C, D, and E of a compound of Formula I, which has been found to be a potent inhibitor of LFA-1, are disclosed. Methods of preparation and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed in this invention. 114-. (canceled) This application is a continuation of U.S. application Ser. No. 12/909,241, filed Oct. 21, 2010 which claims priority from U.S. Provisional Application 61/253,828, filed Oct. 21, 2009, which applications are hereby incorporated by reference in their entirety.The compound of Formula I:has been found to be an effective inhibitor of Lymphocyte Function-Associated Antigen-1 (LFA-1) interactions with the family of Intercellular Adhesion Molecules (ICAM), and has desirable pharmacokinetic properties, including rapid systemic clearance. Improved forms, including crystalline forms, and their uses in treatment of disorders mediated by the interaction of LFA-1 and ICAM are described herein. Novel polymorphs of the compound of Formula I which may afford improved purity, stability, bioavailability and other like characteristics for use in pharmaceutical formulations and methods of use thereof are useful in treating disease.In a first aspect the invention provides methods of making a compound of Formula I:According to the invention, such methods may yield a compound which comprises a purity of greater than about 90%, and its pharmaceutically acceptable salts. In some embodiments, the purity is greater than about 98%. In other embodiments, the compound comprises at least about 95% of an S-enantiomer. In yet other embodiments, the compound is not the calcium salt of the free acid. Alternatively, the compound is a sodium salt.The invention also provides compositions of a compound of Formula I, wherein the compound comprises less than 0.5% of any one byproduct of chemical synthesis of the compound. In other embodiments, the compound comprises less than a total of 1.5% of all byproducts of ...

Azetidine Derivatives

Azetidine derivatives of which the following is exemplary 2. A compound according to whereinX is O, and{'sub': '3', 'R is H or CH.'}3. A compound according to wherein Aris selected from a group consisting of: [{'sup': '1', 'wherein the above-mentioned phenyl, pyridinyl and pyrimidinyl are each substituted with one to three groups independently selected from R, and/or'}, {'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '2, 'wherein two adjacent carbon atoms of a phenyl group may be linked to each other via a —O—CH—O—, —O—CF—O—, —O—CH—CH—O—, —O—CH—CH—CH—CH—, —O—CH—CH—CH—C(CH)—, —O—CH—CH—CH—O— or —O—CH—C(CH)—CH—O— bridge, and'}, {'sub': '3', 'wherein the above-mentioned benzoxazolyl, benzoisoxalyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl and oxazolopyrimidinyl groups are each optionally substituted with Cl, CHor phenyl.'}], 'phenyl, pyridinyl, pyrimidinyl, benzoxazolyl, benzoisoxalyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl and oxazolopyrimidinyl,'}4. A compound according to wherein Ris selected from the group consisting of:{'sub': 1-4', '2-4', '3-7', '3-7', '2', '1-4', '3-7', '3-7', '1-3', '1-4', '2', '1-4', '2, 'sup': N1', 'N2, 'claim-text': wherein each alkyl, cycloalkyl and heterocyclyl may be optionally substituted with one to three substituents independently selected from the group consisting of F and CN, and', {'sub': '3', 'wherein each phenyl and pyridinyl group may be optionally substituted with one F or —OCH.'}], 'H, F, Cl, Br, CN, OH, C-alkyl, C-alkenyl, C-cycloalkyl, C-cycloalkyl-CH—, C-alkyl-O—, C-cycloalkyl-O—, C-cycloalkyl-C-alkyl-O—, C-alkyl-S(═O), RRN—, HO—C(═O)—, C-alkyl-O—C(═O)—, phenyl, phenyl-O—, phenyl-CH—O—, pyridinyl,'}5. A compound according to wherein Aris selected from the group consisting of:{'sup': '2', 'claim-text': {'sup': '2', 'sub': 1-2', '1-2', '1-3', '2, 'wherein Ris F, Cl, C-alkyl-, C-alkyl-O—, C-alkyl-C(═O)—NH or HO—CH—C(═O)—NH—.'}, 'phenylene and ...

Aminodihydrothiazine derivatives

A composition having BACE 1 inhibitory activity containing a compound represented by the general formula (I): wherein ring A is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; E is lower alkylene; X is S, O, or NR′; R 1 is a hydrogen atom or lower alkyl; R 2a , R 2b , R 3a , R 3b , R 4a and R 4b is each independently a hydrogen atom, halogen, or hydroxy etc.; n and m are each independently an integer of 0 to 3; n+m is an integer of 0 to 3; R 5 is a hydrogen atom or substituted lower alkyl; its pharmaceutically acceptable salt, or a solvate thereof.

Small Molecule Modulators of HIV-1 Capsid Stability and Methods Thereof

The present invention includes a method of inhibiting, suppressing or preventing a viral infection in a subject, comprising administering to the subject a pharmaceutical composition comprising one or more of the compounds useful within the invention. 2. The composition of claim 1 , wherein in Formula (III) Rand Rare such that:{'sup': 5', '4, '(i) if ‘a’ is a double bond and ‘b’ is a single bond, then Ris N or CH, and Ris NH or N-alkyl, or'}{'sup': 5', '4, '(ii) if ‘a’ is a single bond and ‘b’ is a double bond, then Ris NH or N-alkyl, and Ris N or CH.'}3. The composition of claim 2 , wherein in Formula (III) Rand Rare such that:{'sup': 5', '4, '(i) if ‘a’ is a double bond and ‘b’ is a single bond, then Ris N, and Ris NH or N-alkyl, or'}{'sup': 5', '4, '(ii) if ‘a’ is a single bond and ‘b’ is a double bond, then Ris NH or N-alkyl, and Ris N.'}4. The composition of claim 1 , wherein said compound is 4-(4 claim 1 ,5-diphenyl-1H-imidazol-2-yl)benzoic acid (CMPD-E) or a salt thereof.5. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.7. The composition of claim 6 , wherein said compound is 4-(5-(dibenzo[b claim 6 ,d]furan-2-yl)-4-phenyl-1H-imidazol-2-yl)benzoic acid (CMPD-C) or a salt thereof.8. The composition of claim 6 , further comprising a pharmaceutically acceptable carrier.12. The method of claim 9 , wherein in said compound of Formula (III) Rand Rare such that:{'sup': 5', '4, '(i) if ‘a’ is a double bond and ‘b’ is a single bond, then Ris N, and Ris NH or N-alkyl, or'}{'sup': 5', '4, '(ii) if ‘a’ is a single bond and ‘b’ is a double bond, then Ris NH or N-alkyl, and Ris N.'}13. The method of claim 9 , wherein said compound is selected from the group consisting of 4 claim 9 ,4′-(5 claim 9 ,5′-(dibenzo[b claim 9 ,d]furan-2 claim 9 ,8-diyl)bis(4-phenyl-1H-imidazole-5 claim 9 ,2-diyl))dibenzoic acid (CMPD-A) claim 9 , dimethyl 4 claim 9 ,4′-(5 claim 9 ,5′-(dibenzo[b claim 9 ,d]furan-2 claim 9 ,8-diyl)bis(4-phenyl-1H-imidazole-5 ...

New azetidine derivatives, pharmaceutical compositions and uses thereof

The invention relates to new azetidine derivatives of the formula I 2. A compound according to claim 1 , whereinR is H; and{'sup': '2', 'Aris phenylene.'}3. A compound according to claim 1 , wherein L is a straight chain C-alkylene group which is optionally substituted with one methyl group.4. A compound according to claim 1 , wherein{'sup': '1', 'Aris selected from the group consisting of {'sup': '1', 'wherein each of the beforementioned groups may be substituted with one or two substituents R.'}, 'phenyl, thiadiazolyl, pyridinyl, pyrimidinyl, pyridazinyl, quinolinyl, oxazolo[4,5-d]pyrimidinyl, 2,3-dihydro-benzo[1,4]dioxinyl and 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl,'}6. A compound according to claim 1 , wherein{'sup': '1', 'Ris selected from a group consisting of{'sub': 1-4', '3-5', '1-4', '3-6', '3-5', '2', '2, 'claim-text': wherein each alkyl and cycloalkyl group may be substituted by one to three F; and', {'sub': '2', 'wherein in the NH-group, one or both hydrogen atoms may independently be replaced by C1-4-alkyl or C3-5-cycloalkyl, wherein each alkyl and cycloalkyl group may be substituted by one or more F; and'}, {'sub': '3', 'wherein each phenyl group may be substituted by Cl or —OCH.'}], 'F, Cl, Br, C-alkyl, C-cycloalkyl, C-alkyl-O—, C-cycloalkyl-O—, C-cycloalkyl-CH—O—, HN—, thiophenyl and phenyl,'}7. A compound according to claim 1 , whereinT is selected from a group consisting of:{'sub': 1-3', '1-2', '1-2', '1-2', '2', '3-5', '3-5', '2-6', '2-6', '2, 'claim-text': wherein the heterocyclyl group is selected from the group consisting of: pyrrolidinyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl; and', 'and wherein each heteroaryl group is selected from the group consisting of: pyrrolyl, furanyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridyzinyl; and', {'sub': '2', 'wherein in each heterocyclyl a —CH-group may optionally be replaced by —C(═O)—; and'}, {'sub': 1-3', '1-3', ...

C5ar antagonists

Compounds are provided that are modulators of the C5a receptor. The compounds are substituted piperidines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activation of C5a receptors.

Dihydropyrazoles

Novel dihydropyrazole derivatives of formula (I) 2. The compound according to claim 1 , wherein R claim 1 , L denote Ar.3. The compound according to claim 1 , wherein{'sup': 1', '2', '3', '4, 'X, X, X, Xdenote a single bond, and'}m denotes 0.4. The compound according to claim 1 , wherein{'sup': 1', '1', '2, 'Ardenotes an aromatic, monocyclic carbocycle having 5-8 C atoms, which is mono-, di- or trisubstituted by at least one substituent selected from the group of Rand R.'}5. The compound according to claim 1 , wherein{'sup': '1', 'Hetdenotes an unsaturated or aromatic monocyclic heterocycle having 3-6 C atoms and 1-3 N, O and/or S atoms, which is substituted by at least one substituent selected from the group of Hal, A and OA.'}9. A pharmaceutical composition comprising at least one compound according to and/or a physiologically acceptable salt thereof.10. The pharmaceutical composition according to claim 9 , comprising pharmaceutically tolerable adjuvants for oral administration.11. The pharmaceutical composition according to claim 9 , comprising at least a second active pharmaceutical ingredient.13. The method according to claim 12 , wherein an effective amount of at least one compound and/or a physiologically acceptable salt thereof is administered to a mammal in need of treating fertility disorders. This application claims the benefit of U.S. Provisional application Ser. No. 61/503,694 filed on Jul. 1, 2011, which is hereby incorporated by reference.The present invention relates to compounds of formula (I)wherein L, R, R, R, R, R, R, X, X, X, X, Y, m and n have the meaning according to the claims, and/or physiologically acceptable salts thereof. The compounds of formulas (I) can be used as positive allosteric modulators of the follicle stimulating hormone receptor (FSHR). Objects of the invention are also pharmaceutical compositions comprising the compounds of formula (I), and the use of the compounds of formula (I) for the treatment of fertility disorders. ...

5-membered heterocycle-based p38 kinase inhibitors

Provided are 5-membered heterocycle-based p38 kinase inhibitors. Further provided are pyrazole and imidazole-based p38 kinase, including p38α, and p38β kinase, inhibitors. Pharmaceutical compositions containing the compounds are also provided. Methods of use of the compounds and compositions are also provided, including methods of treatment, prevention, or amelioration of one or more symptoms of p38 kinase mediated diseases and disorders, including, but not limited to, inflammatory diseases and disorders.

Pyrazole Compounds

Aryl substituted pyrazole derivatives are provided, as well as processes for their preparation. The invention also provides compositions and methods for the treatment of HCV by administering a compound of the present invention, alone or in combination with additional antiviral agents, in a therapeutically effective amount. 157-. (canceled)72. A method of treating HCV infection in a human comprising administering a therapeutically effective amount of a compound of according to .73. A method of treating HCV infection in a human comprising administering a therapeutically effective amount of a compound of according to .74. A method of treating HCV infection in a human comprising administering a therapeutically effective amount of a compound of according to .75. A method of treating HCV infection in a human comprising administering a therapeutically effective amount of a combination of the compound according to claim 58 , or a therapeutically acceptable salt or hydrate thereof claim 58 , and at least one additional agent selected from an interferon claim 58 , ribavirin claim 58 , an HCV protease inhibitor claim 58 , an HCV polymerase inhibitor claim 58 , an HCV IRES inhibitor claim 58 , an HCV Helicase claim 58 , an HCV ATPase inhibitor claim 58 , an NS5A phosphorylation inhibitor claim 58 , and an HCV NS2 inhibitor.76. A pharmaceutical composition for the treatment of HCV infection comprising a therapeutically effective amount of a compound of according to in a pharmaceutically acceptable carrier.77. The pharmaceutical composition of claim 76 , further comprising a second antiviral agent claim 76 , wherein the second anti-viral agent is selected from the group consisting of an interferon claim 76 , ribavirin claim 76 , an HCV protease inhibitor claim 76 , an HCV polymerase inhibitor claim 76 , an HCV IRES inhibitor claim 76 , an HCV Helicase claim 76 , an HCV ATPase inhibitor claim 76 , an NS5A phosphorylation inhibitor claim 76 , and an HCV NS2 inhibitor. Strategies in ...

Naphthalene Derivative

The present invention provides compounds which can regulate VCP activity. The present invention provides the compound of formula (I) 2. The compound according to or oxides , esters , prodrugs , pharmaceutically acceptable salts or solvates thereof , wherein R is selected from phenyl , pyridyl , quinolinyl and thiophenyl , and may be unsubstituted or independently of one another substituted with one or more Ra , in which Ra is as defined in .3. The compound according to or oxides , esters , prodrugs , pharmaceutically acceptable salts or solvates thereof , wherein Ra is absent or independently of one another selected from the group consisting of halo , alkyl , substituted alkyl , alkenyl , substituted alkenyl , aryl , substituted aryl , heteroaryl , substituted heteroaryl , heterocyclyl , substituted heterocyclyl , cyano , nitro , acyl , acylamino , alkoxy , substituted alkoxy , carboxyl , carboxyl ester , alkylthio , substituted alkylthio and aminocarbonyl , in which the substituted alkyl , the substituted alkenyl , the substituted aryl , the substituted heteroaryl , the substituted heterocyclyl , the substituted alkoxy or the substituted alkylthio independently of one another refer to the respective groups substituted with one or more substituent Rb or Rc , the substituent Rb and Rc being as defined in .6. The compound according to or oxides , esters , prodrugs , pharmaceutically acceptable salts or solvates thereof , wherein Ra is selected from the group consisting of alkenyl , substituted alkenyl , aryl , substituted aryl , heteroaryl , substituted heteroaryl , cyano , carboxyl ester , alkylthio , substituted alkylthio and aminocarbonyl , in which substituted alkenyl , substituted aryl , substituted heteroaryl , substituted alkylthio independently of one another refer to the respective groups substituted with one or more substituent Rb or Rc , the substituent Rb and Rc being as defined in .7. A pharmaceutical composition comprising the compound according to or ...

BENZODIOXANE INHIBITORS OF LEUKOTRIENE PRODUCTION

The present invention relates to compounds of formula (I): 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein group A is a group of formula —NRR.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H or —(C-C)alkyl claim 1 , and Ris —(C-C)alkyl; wherein each —(C-C)alkyl of said Rand Rgroups claim 1 , when present claim 1 , is optionally independently substituted by one to three Rgroups.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H or —(C-C)alkyl claim 1 , and Ris —(C-C)alkyl; wherein said —(C-C)alkyl of said Rgroup is substituted by —(C-C)cycloalkyl claim 1 , -(4- to 11-membered)heterocycloalkyl claim 1 , —(C-C)aryl claim 1 , or -(5- to 11-membered)heteroaryl; wherein each of said claim 1 , —(C-C)cycloalkyl claim 1 , -(4- to 11-membered)heterocycloalkyl claim 1 , —(C-C)aryl claim 1 , and -(5- to 11-membered)heteroaryl is optionally substituted with one to three groups independently selected from —(C-C)alkyl claim 1 , —CF claim 1 , and —C(O)OR.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H or —(C-C)alkyl claim 1 , and Ris —(C-C)alkyl; wherein said —(C-C)alkyl of said Rgroup is independently substituted by one to three groups selected from —(C-C)alkyl claim 1 , —O(C-C)alkyl claim 1 , —C(O)R claim 1 , —C(O)OR claim 1 , —S(O)R claim 1 , and —NHC(O)R.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare each independently selected from —H or —(C-C)alkyl.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H or —(C-C)alkyl claim 1 , and Ris —(C-C)cycloalkyl claim 1 , -(4- to 11-membered)heterocycloalkyl claim 1 , —(C-C)aryl claim 1 , and -(5- to 11-membered)heteroaryl; wherein each of the foregoing —(C-C)cycloalkyl claim 1 , -(4- to 11-membered)heterocycloalkyl claim 1 , —(C-C)aryl claim 1 ...

Benzimidazole Derivatives As PI3 Kinase Inhibitors

This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer. 116.-. (canceled) This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer.The phosphoinositide 3-kinase (PI3K) pathway is among the most commonly activated in human cancer and the importance in carcinogenesis is well established (Samuels Y and Ericson K. Oncogenic PI3K and its role in cancer. 2006; 18:77-82). Initiation of signaling begins with the phosphorylation of phosphatidylinositol-4,5-bisphosphate (PIP2) to produce phosphatidylinositol-3,4,5-P3 (PIP3). PIP3 is a critical second messenger which recruits proteins ...

CYCLOPROPYLAMINE DERIVATIVES USEFUL AS LSD1 INHIBITORS

The invention relates to cyclopropylamine compounds, in particular the compounds of Formula (I), and their use in therapy, including e.g. in the treatment or prevention of cancer, a neurological disease or condition, or viral infection. 4. The compound of wherein (G) is a heterocyclyl.5. (canceled)6. The compound of wherein (G) is phenyl.78-. (canceled)9. The compound of wherein E is —X═X— claim 1 , and X claim 1 , X claim 1 , Xand Xare independently C(R2) or N.10. The compound of wherein E is —X═X— claim 1 , and X claim 1 , X claim 1 , Xand Xare independently C(R2).1112-. (canceled)13. The compound of wherein E is —S— claim 1 , and Xand Xare independently C(R2) or N.1420-. (canceled)21. The compound of wherein each (R1) is independently chosen from alkyl claim 1 , aryl claim 1 , amino claim 1 , amido claim 1 , nitro claim 1 , halo claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , cyano claim 1 , heterocycle claim 1 , sulfonyl claim 1 , sulfonamide claim 1 , hydroxyl claim 1 , or alkoxy.22. The compound of wherein each (R1) is independently chosen from —CF claim 1 , —F claim 1 , —Cl claim 1 , —CN claim 1 , —CH claim 1 , —OH claim 1 , —OCH claim 1 , —C(═O)NH claim 1 , —NH—CO—CH claim 1 , —NH—SO—CH claim 1 , —NH—SO—CH—CH claim 1 , —NH—SO—CH(CH)—CH claim 1 , —NH—SO—(CH) claim 1 , —NH—SO—(CH)—CN claim 1 , —NHSOCF claim 1 , or —S(═O)NHCH.2328-. (canceled)30. The compound of wherein E is —S— or —X═X—.3137-. (canceled)38. The compound of wherein (G) is an aryl or heterocyclyl.3941-. (canceled)42. The compound of wherein each (R1) is independently chosen from alkyl claim 29 , aryl claim 29 , amino claim 29 , amido claim 29 , nitro claim 29 , halo claim 29 , haloalkyl claim 29 , cyano claim 29 , heterocyclyl claim 29 , sulfonyl claim 29 , sulfonamide claim 29 , hydroxyl claim 29 , or alkoxy.4446-. (canceled)47. The compound of wherein (G) is an aryl or heterocyclyl.4850-. (canceled)51. The compound of wherein each (R1) is independently chosen from alkyl claim 43 , aryl ...

THIOACETATE COMPOUNDS, COMPOSITIONS AND METHODS OF USE

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of 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. 2. A compound of claim 1 , wherein one of X claim 1 , X claim 1 , Xor Xis N.4. A compound of claim 1 , wherein two of X claim 1 , X claim 1 , Xor Xare N.7. A compound of claim 1 , wherein{'sup': '3', 'sub': 3', '3', '3, 'Ris H, CH, OCH, CF, F or Cl; and'}{'sup': '4', 'sub': 3', '3', '3, 'Ris H, CH, OCH, CF, F or Cl.'}8. A compound of claim 7 , wherein Rand Rare both H.9. A compound of claim 1 , wherein Rand Rtogether with the carbon atoms to which they are attached form an optionally substituted 5- or 6-membered ring claim 1 , optionally containing one or two heteroatoms selected from O claim 1 , N and S claim 1 , wherein said 5- or 6-membered ring maybe a saturated claim 1 , an unsaturated or an aromatic ring.10. A compound of claim 1 , wherein Rand Rtogether with the carbon atoms to which they are attached form an optionally substituted claim 1 , 6-membered aromatic ring.12. A compound of claim 1 , wherein{'sup': 'a', 'sub': '3', 'Ris H or CH; and'}{'sup': 'b', 'sub': '3', 'Ris H or CH.'}13. A compound of claim 12 , wherein Rand Rare both CH.15. A compound of claim 14 , wherein{'sup': '1', 'Xis CH;'}{'sup': '2', 'Xis N;'}{'sup': '3', 'Xis CH; and'}{'sup': '4', 'Xis CH.'}16. A compound of claim 15 , wherein{'sup': 1', '1, 'Yis CR; and'}{'sup': 2', '2, 'Yis CR.'}17. (canceled)19. A compound of claim 18 , wherein R claim 18 , Rand Rare all H.20. A compound of claim 1 , wherein Rand Rtogether with the carbon atom to which they are attached form a 3- claim 1 , 4- claim 1 , 5- or 6-membered ring claim 1 , optionally containing one or two heteroatoms selected from O claim 1 , N and S.21. A compound of claim 20 , wherein Rand Rtogether with the carbon atom to which they are attached form a 3- ...

INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

Compounds of formula I: 6. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris (C)alkyl claim 1 , —CN claim 1 , halo or (C)haloalkyl.7. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CH.11. A pharmaceutical composition comprising a compound of formula (I) according to any one of to claim 1 , or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable carriers.12. A method of treating HIV infection which comprises administering to a host infected by HIV a therapeutically effective amount of a compound of formula (I) according to any one of to claim 1 , or a pharmaceutically acceptable salt thereof. This application claims benefit of U.S. Ser. No. 61/178,551, filed May 15, 2009, and U.S. Ser. No. 61/285,766, filed Dec. 11, 2009, which are herein incorporated by reference.The present invention relates to compounds, compositions and methods for the treatment of human immunodeficiency virus (HIV) infection. In particular, the present invention provides novel inhibitors of the HIV integrase enzyme, pharmaceutical compositions containing such compounds and methods for using these compounds to reduce HIV replication and in the treatment of HIV infection.Acquired immune deficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV), particularly the HIV-1 strain. Most currently approved therapies for HIV infection target the viral reverse transcriptase and protease enzymes. There are also two approved drugs targeting HIV entry and one approved drug targeting the integrase enzyme. Within the reverse transcriptase inhibitor and protease inhibitor classes, resistance of HIV to existing drugs is a problem. Therefore, it is important to discover and develop new antiretroviral compounds.International patent application WO 2007/131350 and United States published patent application US 2006/0106070 describe compounds which are active ...

Thioacetate compounds, compositions and methods of use

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of 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.

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 ...

PROLYL HYDROXYLASE INHIBITORS AND METHODS OF USE

The present disclosure relates to HIF-1α prolyl hydroxylase inhibitors, compositions which comprise the HIF-1α prolyl hydroxylase inhibitors described herein and to methods for controlling, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, and anemia. 132-. (canceled)34. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00033', 'claim 33'}, 'A) the compound according to ; and'}B) one or more pharmaceutically acceptable excipients.35. A method for treating anemia comprising administering to a human or mammal in need of treatment and effective amount of the compound according to .37. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00036', 'claim 36'}, 'A) the compound according to ; and'}B) one or more pharmaceutically acceptable excipients.38. A method for promoting wound healing comprising administering to a human or mammal in need of treatment and effective amount of the compound according to .40. The compound according to claim 39 , chosen from:{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid methyl ester;{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid ethyl ester;5-(3-Chlorophenyl)-N-(2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;5-(3-Chlorophenyl)-N-(2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;5-(3-Chlorophenyl)-N-(2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;{[5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid methyl ester;{[5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid ethyl ester;5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide; and5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-(2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide.41. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM- ...

QUINAZOLINONE-TYPE COMPOUNDS AS CRTH2 ANTAGONISTS

This application provides for compounds of the formula Formula I or a pharmaceutically acceptable salt thereof, wherein the individual variables are defined herein, as well as processes to prepare these compounds, pharmaceutical compositions comprising the same and their use in treating disease state associated with the CRTHreceptor. 12. A pharmaceutical composition comprising an effective amount of a compound of Formula I according to or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.13. The pharmaceutical composition according to which further comprises an effective amount of at least one additional therapeutic agent.14. A method for treating a disease state associated with the CRTHreceptor in a mammal in need of such treatment which comprises administering to said mammal and effective amount of a compound of Formula I as defined in or a pharmaceutically acceptable salt thereof.15. The method according to claim 14 , wherein the disease state is asthma claim 14 , congestion claim 14 , allergic rhinitis or COPD. This application relates to quinazolinone-type compounds, compositions comprising these compounds, their use as antagonists of the chemoattractant receptor-homologous molecule expressed on T-helper-type-2 cells (CRTH) and to processes for preparing these compounds.CRTHreceptor antagonists are useful in the treatment and prevention of both chronic and acute allergic/immune prostaglandin-mediated disorders and diseases such as, for example, asthma, congestion, allergic rhinitis, atopic dermatitis, chronic obstructive pulmonary disease (COPD), dermatitis, inflammatory bowel disease, rheumatoid arthritis, allergic nephritis, conjunctivitis, bronchial asthma, fold allergy, systemic mast cell disorder, anaphylactic shock, urticaria, eczema, itching, inflammation, ischemia-reperfusion injury, cerebrovascular disorders, pleuritis, ulcerative colitis, eosinophil-related diseases, such as Churg-Strauss syndrome and sinusitis, and ...

COMPOUNDS FOR MODULATING RNA BINDING PROTEINS AND USES THEREFOR

The invention relates to compositions and methods for inhibiting RNA binding proteins (e.g., MEX-3, MEX-5 and POS-1), as well as methods for treating and preventing disorders associated with parasitic infections and inflammatory disorders. 1. A method for treating or preventing a parasitic associated state in a subject comprising administering to said subject an effective amount of an RNA binding modulatory compound , such that said parasitic associate state is treated or prevented.3. The method of claim 1 , wherein the RNA binding modulatory compound is a compound of Table 1 or Table 2 claim 1 , and pharmaceutically acceptable salts thereof.4. The method of claim 1 , wherein said subject is a plant claim 1 , an animal or a human.56-. (canceled)7. The method of claim 1 , wherein said parasitic associated state is a parasitic infestation or parasitic re-infestation or a disease caused by a parasitic infestation.8. (canceled)9. The method of claim 1 , wherein said method includes protecting plants from a parasitic infestation claim 1 , inhibiting embryogenesis in a parasite or in a subject suffering from a parasitic infestation claim 1 , or reducing parasitic burden in soil claim 1 , in plants or in an animal suffering from a parasitic infection.10. The method of claim 1 , wherein said parasite is a helminth.11. The method of claim 10 , wherein said helminth is selected from the group consisting of a cestode claim 10 , a trematode and a nematode.12. (canceled)13. A method for inhibiting embryogenesis in a parasite claim 10 , comprising contacting said parasite with an effective amount of an RNA binding modulatory compound claim 10 , such that said embryogenesis is inhibited.15. The method of claim 13 , wherein the RNA binding modulatory compound is a compound of Table 1 or Table 2 claim 13 , and pharmaceutically acceptable salts thereof.16. The method of claim 13 , wherein the parasite is present in a subject.1719-. (canceled)20. The method of claim 13 , wherein said ...

WOGONIN FOR THE PREVENTION AND THERAPY OF CARDIAC HYPERTROPHY

The present invention relates to a pharmaceutical composition for use as a medicament for the treatment or prophylaxis of cardiac hypertrophy, comprising at least one compound of formula (I), wherein: Ris e.g. hydrogen, —CH, Ris e.g. hydrogen, —CH, Ris hydrogen, —OH, —NH; Ris hydrogen, —OH; Ris hydrogen, —OH; Ris e.g. —OCHor a pharmaceutically acceptable salt, and at least one pharmaceutical excipient. 3. A pharmaceutical composition for use as a medicament for the treatment and/or prophylaxis of cardiac hypertrophy claim 1 , comprising at least one compound of formula (I) claim 1 , according to claim 1 , wherein the composition comprises at least one compound of formula (I) claim 1 , in which Rdenotes —OCH claim 1 , or a pharmaceutically acceptable salt or an isomeric or polymorphic form thereof.4. A pharmaceutical composition for use as a medicament for the treatment and/or prophylaxis of cardiac hypertrophy claim 1 , according to claim 1 , comprising from 0.1 to 2000 mg of the compound Wogonin (W) and at least one pharmaceutically acceptable excipient.6. A pharmaceutical composition according to claim 5 , comprising as compound of formula (I) the drug compound Wogonin (W) and as second drug compound at least one from the following group: ACE inhibitors claim 5 , beta blockers claim 5 , anti-hypertensives claim 5 , cardiotonics claim 5 , anti-thrombotics claim 5 , vasodilators claim 5 , hormone antagonists claim 5 , ionotropes claim 5 , diuretics claim 5 , endothelin antagonists claim 5 , calcium channel blockers claim 5 , phosphordiesterase inhibitors claim 5 , angiotensin type II antagonists and cytokine inhibitors.7. A pharmaceutical composition according to claim 5 , comprising as compound of formula (I) the drug compound Wogonin (W) and as second drug compound an ACE inhibitor from the group ramipril claim 5 , alacepril claim 5 , enalapril claim 5 , captopril claim 5 , cilazapril claim 5 , delapril claim 5 , enalaprilat claim 5 , fosinopril claim 5 , ...

GLUCOSYLCERAMIDE SYNTHASE INHIBITION FOR THE TREATMENT OF COLLAPSING GLOMERULOPATHY AND OTHER GLOMERULAR DISEASE

A method of treating a glomerular disease selected from the group consisting of mesangial proliferative glomerulonephritis, collapsing glomerulopathy, proliferative lupus nephritis, crescentic glomerulonephritis and membranous nephropathy in a subject comprises administering to the subject an effective amount of a glucosylceramide synthase inhibitor. 183.-. (canceled)84. The method of claim 89 , wherein the glomerular disease is mesangial proliferative glomerulonephritis.85. The method of claim 89 , wherein the glomerular disease is collapsing glomerulopathy.86. The method of claim 89 , wherein the glomerular disease is proliferative lupus nephritis.87. The method of claim 89 , wherein the glomerular disease is crescentic glomerulonephritis.88. The method of claim 89 , wherein the glomerular disease is membranous nephropathy.91. The method of claim 89 , wherein Q is —O— or —C(O)—.95. The method of claim 94 , wherein Q is —O— or —C(O)—.97. The method of claim 89 , wherein Ris a phenyl group optionally substituted with one or more substituents selected from the group consisting of halogen claim 89 , cyano claim 89 , nitro claim 89 , C1-C6 alkyl claim 89 , C1-C6 haloalkyl claim 89 , C1-C6 alkylamino claim 89 , C1-C6 dialkylamino claim 89 , aryl claim 89 , aryloxy claim 89 , —OH claim 89 , C1-C6 alkoxy claim 89 , —O—[CH]—O— and —[CH]—.104. The method of claim 89 , wherein the compound is a (1R claim 89 ,2R) stereoisomer claim 89 , or a pharmaceutically acceptable salt thereof.107. The method of claim 106 , wherein the compound is a (1R claim 106 ,2R) stereoisomer claim 106 , or a pharmaceutically acceptable salt thereof. This application is a continuation of U.S. application Ser. No. 13/055,036, filed Mar. 17, 2011, which is the U.S. National Stage of International Application No. PCT/US2009/051864, filed Jul. 27, 2009, published in English, which claims the benefit under 35 U.S.C. §119 or 365 of U.S. Provisional Application No. 61/137,214, filed Jul. 28, 2008. The ...

ANTIMETASTATIC COMPOUNDS

Screening methods for identifying compounds and compounds and pharmaceutical compositions for treating and preventing cancer are disclosed. The compounds affect signal transduction downstream of the MET receptor. 228-. (canceled)34. The method according to claim 29 , wherein A is S and B is CH.35. The method according to claim 29 , wherein A is NH and B is CH.36. The method according to claim 29 , wherein A is absent and B is CH—CH.37. The method according to claim 29 , wherein A is absent and B is CH═CH.38. The method according to claim 29 , wherein A is S and B is CHCH═CH.39. The method according to claim 29 , wherein A is absent and B is CH—CH—CH.40. The method according to claim 29 , wherein n is 0.41. The method according to claim 29 , wherein n is 1.42. The method according to claim 29 , wherein R is H.43. The method according to claim 29 , wherein R is phenyl.44. The method according to claim 29 , wherein R is benzyl.45. The method according to claim 29 , wherein Y is alkyl.46. The method according to claim 29 , wherein Y is alkenyl.47. The method according to claim 29 , wherein Y is alkoxy.48. The method according to claim 29 , wherein Y is hydroxy.49. The method according to claim 29 , wherein Y is unsubstituted aryl.50. The method according to claim 29 , wherein Y is substituted aryl.51. The method according to claim 29 , wherein Y is heterocycle.52. The method according to claim 29 , wherein Y is selected from 1H-benzo[de]isoquinoline-1 claim 29 ,3-(2H)-dione claim 29 , 3 claim 29 ,5-dimethylisoazole claim 29 , 2-methylthiazole claim 29 , pyrrolidine claim 29 , and 3 claim 29 ,5-dimethylisoxazole.53. The method according to claim 29 , wherein Rand Rwhen present claim 29 , form a carbocyclic ring.54. The method according to claim 29 , wherein Rand Rwhen present claim 29 , form a carbocyclic ring selected from fused cyclohexene claim 29 , fused cyclopentene claim 29 , and fused dihydronaphthalene.5577-. (canceled) The present invention relates to screening ...

ALDH-2 INHIBITORS IN THE TREATMENT OF ADDICTION

Disclosed are novel isoflavone derivatives having the structure of Formula I: 2. The compound of claim 1 , wherein Ris optionally substituted alkyl and Ris optionally substituted alkyl or optionally substituted cycloalkyl.3. The compound of claim 2 , wherein Ris alkyl of 1-6 carbon atoms optionally substituted by halo claim 2 , hydroxyl claim 2 , cyano claim 2 , optionally substituted alkoxy of 1-6 carbon atoms claim 2 , optionally substituted acyl claim 2 , optionally substituted amino claim 2 , optionally substituted carboxylalkyl claim 2 , optionally substituted carboxylcycloalkyl claim 2 , or optionally substituted alkoxycarbonylamino.4. The compound of claim 3 , wherein X claim 3 , Y and Z are —CR— and Ris hydrogen claim 3 ,{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, 'The compound of , selected from the group consisting ofN-(4-(7-(3-methoxyprop-1-ynyl)-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide;N-(4-(7-(3-hydroxy-3-methylbut-1-ynyl)-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide; andN-(4-(7-(3-methoxyprop-1-ynyl)-4-oxo-4H-chromen-3-yl)phenyl)cyclopropane-sulfonamide.5. The compound of claim 1 , wherein Ris optionally substituted cycloalkyl and Ris optionally substituted alkyl or optionally substituted cycloalkyl.6. The compound of claim 5 , wherein Ris cycloalkyl optionally substituted by halo claim 5 , hydroxyl claim 5 , cyano claim 5 , alkoxy claim 5 , optionally substituted acyl claim 5 , optionally substituted amino claim 5 , optionally substituted carboxylalkyl claim 5 , optionally substituted carboxylcycloalkyl claim 5 , or optionally substituted alkoxycarbonylamino.7. A compound of claim 6 , wherein X claim 6 , Y and Z are —CR— and Ris hydrogen claim 6 ,8. A compound of claim 1 , selected from the group consisting of:N-(4-(7-(cyclopropylethynyl)-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide;N-(4-(7-(((1S,2R)-2-hydroxycyclopentyl)ethynyl)-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide;N-(4-(7-((1-hydroxycyclopentyl)ethynyl)-4-oxo-4H-chromen ...

6-alkenyl and 6-phenylalkyl substituted 2-quinolinones and 2-quinoxalinones as poly(adp-ribose) polymerase inhibitors

The present invention provides compounds of formula (I) and compounds of formula (VII-a) as well as pharmaceutical compositions comprising said compounds and their use as PARP inhibitors wherein n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R e , R d and X have defined meanings.

HETEROCYCLIC MODULATORS OF CANNABINOID RECEPTORS

Heterocyclic compounds which modulate cannabinoid receptors are presented. Pharmaceutical compositions containing these compounds, methods of using these compounds as modulators of cannabinoid receptors and processes for synthesizing these compounds are also described herein. 138-. (canceled) This application claims priority to U.S. Pat. App. Ser. No. 60/949,536 filed Jul. 13, 2007 and to U.S. Pat. App. Ser. No. 61/036,321 filed Mar. 13, 2008. These applications are incorporated by reference herein it their entirety.The present invention is directed to new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of modulating cannabinoid receptor activity in human or animal subject are provided for the treatment of diseases.None.None.None.CB1 and CB2 are two cannabinoid receptors that belong to the GPCR family and have very different functions and distribution. While no x-ray structure is available for these receptors, various models have been described on the basis of the x-ray structure of rhodopsin, a GPCR belonging protein responsible of the light sensitivity in vision. Matsuda L A, Lolait S J, Brownstein M J, Young A C, Bonner T I, , Nature 1990, 346:561-4. CB1 is abundantly expressed in the central nervous system and is most dense in the basal ganglia, cerebellum, hippocampus, and cortex and in the peripheral nervous system, it is expressed in such sites as the testis, eye, urinary bladder, and adipocytes. CB2 is mainly expressed in the immune tissues, in cells such as those in the thymus, marrow, spleen, pancreas, and in glioma and skin tumor cells. It was recently demonstrated that CB2 receptors and their gene transcripts are widely distributed in the brain. A third cannabinoid receptor seems to be present as some chemical analogues exhibit cannabinoid biological activity without activating CB1 and CB2. Di Marzo V, Bifulco M, De Petrocellis L, , Nat Rev Drug Discov 2004, 3:771-84.Novel ...

BENZODIOXANE INHIBITORS OF LEUKOTRIENE PRODUCTION

The present invention relates to compounds of formula (I): 5. A pharmaceutical composition comprising one or more compounds of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier or excipient.6. A pharmaceutical composition comprising one or more compounds of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , and a pharmaceutically acceptable carrier or excipient.7. A pharmaceutical composition comprising one or more compounds of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , and a pharmaceutically acceptable carrier or excipient.8. A pharmaceutical composition comprising one or more compounds of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , and a pharmaceutically acceptable carrier or excipient.9. The pharmaceutical composition of claim 1 , further comprising at least one additional pharmacologically active substance.10. A method of treating leukotriene-mediated disorders comprising administering a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to a patient in need thereof.11. The method of claim 10 , wherein the leukotriene-mediated disorder is a cardiovascular disease.12. A method of treating leukotriene-mediated disorders comprising administering the pharmaceutically composition of claim 5 , to a patient in need thereof.13. The method of claim 12 , wherein the leukotriene-mediated disorder is a cardiovascular disease. This invention relates to benzodioxanes that are useful as inhibitors of leukotriene Ahydrolase (LTAH) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of leukotrienes including asthma, allergy and cardiovascular diseases including atherosclerosis, myocardial infarction and stroke. This invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds ...

COMPOUNDS THAT MODULATE INTRACELLULAR CALCIUM

Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity. 118.-. (canceled)22. The compound of wherein Lis —CHN(H)—.23. The compound of wherein Ris phenyl.24. The compound of wherein Ris phenyl substituted with at least one Rselected from F claim 23 , Cl claim 23 , Br claim 23 , I claim 23 , —CN claim 23 , —OH claim 23 , —CF claim 23 , —OCF claim 23 , —OR claim 23 , —N(R) claim 23 , and C-Calkyl.25. The compound of wherein Ris selected from —CF claim 24 , —OCF claim 24 , —OR claim 24 , C-Calkyl claim 24 , and C-Ccycloalkyl.26. The compound of wherein Ris C-Calkyl.27. The compound of wherein Ris —CFand Ris —CH.28. The compound of wherein Ris C-Chaloalkyl.29. The compound of wherein Ris —CFand Ris —CF.30. The compound of wherein Ris phenyl substituted with at least 2 substituents.31. The compound of wherein Ris phenyl substituted with at least 3 substituents.32. The compound of wherein Ris heteroaryl.33. The compound of wherein heteroaryl is selected from thienyl claim 32 , thianthrenyl claim 32 , furyl claim 32 , pyranyl claim 32 , thiadiazolyl claim 32 , benzothiadiazolyl claim 32 , isobenzofuranyl claim 32 , chromenyl claim 32 , xanthenyl claim 32 , phenoxathiinyl claim 32 , pyrrolyl claim 32 , imidazolyl claim 32 , pyrazolyl claim 32 , isothiazolyl claim 32 , isoxazolyl claim 32 , pyridyl claim 32 , pyrazinyl claim 32 , pyrimidinyl claim 32 , pyridazinyl claim 32 , pyrazolo-pyrimidinyl claim 32 , triazolo-pyrimidinyl claim 32 , imidazo-pyrimidinyl claim 32 , indolizinyl claim 32 , isoindolyl claim 32 , 3H-indolyl claim 32 , indolyl claim 32 , indazolyl claim 32 , purinyl claim 32 , 4H-quinolizinyl claim 32 , isoquinolyl claim 32 , quinolyl claim 32 , ...

(AZA)INDOLE DERIVATIVE AND USE THEREOF FOR MEDICAL PURPOSES

The present invention provides compounds useful as agents for the prevention or treatment of a disease associated with abnormal serum uric acid level which has a uricosuric activity or the like. The present invention relates to (aza)indole derivatives represented by the following general formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of serum uric acid level, prodrugs thereof, or salts thereof. In the formula (I), T represents nitro or cyano and the like; ring J represents aryl or heteroaryl and the like; Q represents carboxy or 5-tetazolyl and the like; Y represents H, OH, NH, halogen, nitro, alkyl, alkoxy and the like; X, Xand Xindependently represent CRor N; Rand Rindependently represent halogen, cyano, haloalkyl, A-D-E-G, —N(-D-E-G)and the like, in the formula, A represents a single bond, O, S and the like; D and G independently represent optionally substituted alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene and the like; E represents a single bond, O, S, COO, SOand the like. 2. An (aza)indole derivative as claimed in claim 1 , wherein X claim 1 , Xand Xindependently represent CRwith the proviso that when two or more Rexist claim 1 , these Rare optionally the same or different from each other claim 1 , or a prodrug thereof claim 1 , or a pharmaceutically acceptable salt thereof.3. An (aza)indole derivative as claimed in claim 1 , wherein T represents cyano claim 1 , or a prodrug thereof claim 1 , or a pharmaceutically acceptable salt thereof.4. An (aza)indole derivative as claimed in claim 1 , wherein Q represents carboxy claim 1 , or a prodrug thereof claim 1 , or a pharmaceutically acceptable salt thereof.5. An (aza)indole derivative as claimed in claim 1 , wherein Y represents a hydrogen atom claim 1 , hydroxy or a halogen atom claim 1 , or a prodrug thereof claim 1 , or a pharmaceutically acceptable salt thereof.6. An (aza)indole ...

HETEROCYCLIC COMPOUNDS FOR TREATING OR PREVENTING DISORDERS CAUSED BY REDUCED NEUROTRANSMISSION OF SEROTONIN, NOREPHNEPHRINE OR DOPAMINE

A heterocyclic compound represented by the general formula (1) or a salt thereof: 6. The heterocyclic compound represented by the general formula (1) or a salt thereof according to claim 5 , which is selected from(4aS,8aR)-1-(4-chlorophenyl)-3,3-dimethyldecahydroquinoxaline,2-chloro-4-((4aS,8aS)-3,3-dimethyloctahydroquinoxalin-1(2H)-yl)benzonitrile,(4aS,8aR)-1-(3-chloro-4-fluorophenyl)-3,3-dimethyldecahydroquinoxaline,(4aS,8aR)-1-(7-fluorobenzofuran-4-yl)-3,3-dimethyldecahydroquinoxaline,5-((4aR,8aS)-3,3-dimethyloctahydroquinoxalin-1(2H)-yl)-1-methyl-1H-indole-2-carbonitrile,(4a′R,8a′S)-4′-(7-methoxybenzofuran-4-yl)octahydro-1′H-spiro[cyclobutane-1,2′-quinoxaline],(4aS,8aR)-1-(6,7-difluorobenzofuran-4-yl)-3,3-dimethyldecahydroquinoxaline,5-((4aS,8aS)-3,3-dimethyloctahydroquinoxalin-1(2H)-yl)-1H-indole-2-carbonitrile,(4aS,8aR)-1-(7-chloro-2,3-dihydro-1H-inden-4-yl)-3,3-dimethyldecahydroquinoxaline,6-((4aS,8aS)-3,3-dimethyloctahydroquinoxalin-1(2H)-yl)-2-naphthonitrile,(4aS,8aS)-3,3-dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-4-yOdecahydroquinoxaline, and(4aS,8aS)-1-(4-(difluoromethoxy)-3-fluorophenyl)-3,3-dimethyldecahydroquinoxaline.7. A pharmaceutical composition comprising a heterocyclic compound represented by the general formula (1) or a salt thereof according to as an active ingredient and a pharmaceutically acceptable carrier.8. A prophylactic and/or therapeutic agent for disorders caused by reduced neurotransmission of serotonin claim 1 , norepinephrine or dopamine claim 1 , comprising as an active ingredient a heterocyclic compound of general formula (1) or a salt thereof according to .9. A prophylactic and/or therapeutic agent according to claim 8 , wherein the disorder is selected from the group consisting of depression claim 8 , depression status caused by adjustment disorder claim 8 , anxiety caused by adjustment disorder claim 8 , anxiety caused by various diseases claim 8 , generalized anxiety disorder claim 8 , phobia claim 8 , obsessive-compulsive disorder ...

PROCESS OF MAKING GYRASE AND TOPOISOMERASE INHIBITORS

The present application is directed to compounds, intermediates and methods for preparing compounds of formula (I) 2. The method of claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , benzyl claim 1 , orp-nitrobenzyl.3. The method of claim 1 , wherein said reaction is conducted in a mixture of dioxane and a buffer at 75° C. to 125° C.4. The method of claim 3 , wherein the buffer is a pH 3.5 buffer and the reaction is conducted at reflux.11. The method of claim 9 , wherein said nitrating the compound of formula (VI) comprises reacting the compound of formula (VI) with NHNOin the presence of a strong acid at about 20° C. to about 50° C. to provide a compound (IV).13. The method of claim 12 , wherein the compound of formula (VII) is enantiomerically enriched.21. The method of claim 20 , further comprising reacting the compound of formula (VII) with a brominating agent in a polar aprotic solvent to afford the compound of formula (VI).22. The method of claim 21 , further comprising nitrating the compound of formula (VI) with a suitable nitrating agent to afford the phenyltetrahydrofuran compound of formula (IV). This application claims the benefit under 35 U.S.C. §119 of U.S. Provisional Patent Application Ser. No. 61/432,990 filed Jan. 14, 2011, the contents of which are incorporated herein by reference.Bacterial resistance to antibiotics has long been recognized, and it is today considered to be a serious worldwide health problem. As a result of resistance, some bacterial infections are either difficult to treat with antibiotics or even untreatable. This problem has become especially serious with the recent development of multiple drug resistance in certain strains of bacteria, such as (SP), , and . The appearance of vancomycin resistant was particularly alarming because vancomycin was formerly the only effective antibiotic for treating this infection, and had been considered for many infections to be the drug of “last resort”. While many other drug-resistant ...

Indole and indazole compounds that activate ampk

The present invention relates to indole and indazole compounds of Formula (I) that activate 5′ adenosine monophosphate-activated protein kinase (AMPK). The invention also encompasses pharmaceutical compositions containing these compounds and methods for treating or preventing diseases, conditions, or disorders ameliorated by activation of AMPK.

IMIDAZOLE COMPOUND PRODUCTION METHOD, IMIDAZOLE COMPOUND, IMIDAZOLE-BASED COMPOUND, ORGANIC METAL COMPLEX, MATERIAL FOR ORGANIC ELECTROLUMINESCENT ELEMENT, ORGANIC ELECTROLUMINESCENT ELEMENT, DISPLAY DEVICE, AND LIGHTING DEVICE

A manufacturing method of an imidazole compound represented by a formula (1) below includes reacting 1-arylimidazole with a halogen-atom substituted compound. For performing this reaction, in a reaction system, a mole number N[mol] of the halogen-atom substituted compound and a total volume V[liter] of an ether solvent having at most 5 carbon atoms satisfy a relationship of V/N≦3. 2. The manufacturing method of the imidazole compound according to claim 1 , wherein{'sub': f2', 'A, 'claim-text': {'br': None, 'i': V', '/N, 'sub': A', 'f2, '≦2\u2003\u2003(2).'}, 'the mole number Nof the compound represented by the formula (2) and the total volume Vsatisfy a relationship of a numerical formula (2) below,'}3. The manufacturing method of the imidazole compound according to claim 1 , wherein{'sub': f2', 'A, 'claim-text': {'br': None, 'i': V', '/N, 'sub': A', 'f2, '≦1\u2003\u2003(3).'}, 'the mole number Nof the compound represented by the formula (2) and the total volume Vsatisfy a relationship of a numerical formula (3) below,'}4. The manufacturing method of the imidazole compound according to claim 1 , whereinthe ether solvent comprising at most 5 carbon atoms is at least one ether solvent selected from tetrahydrofuran, tetrahydropyran, 1,4-dioxane, 1,3-dioxane, diethylether and 1,2-dimethoxyethane.5. The manufacturing method of the imidazole compound according to claim 1 , further comprising:{'sub': f2', 'A, 'implementing a solvent removal treatment of removing the solvent in the reaction system to adjust the relationship between the mole number Nand the total volume V.'}6. The manufacturing method of the imidazole compound according to claim 1 , whereinas a second solvent, at least one solvent selected from an aliphatic hydrocarbon solvent comprising at least 7 carbon atoms, an aromatic hydrocarbon solvent and an ether solvent comprising at least 6 carbon atoms is contained in the reaction system, and{'sub': f2', 'B, 'claim-text': {'br': None, 'b': 0', '1, 'i': V', '/N, ...

ASYMMETRIC SYNTHESES FOR SPIRO-OXINDOLE COMPOUNDS USEFUL AS THERAPEUTIC AGENTS

This invention is directed to asymmetric syntheses of certain spiro-oxindole derivatives, which are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain. 15. The method of wherein the phase transfer catalyst is a quaternary ammonium salt of quinidine or a quaternary ammonium salt of cinchonine.64. The method of wherein the phase transfer catalyst is a quaternary ammonium salt of quinidine or a quaternary ammonium salt of cinchonine. This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 61/623,336, filed Apr. 12, 2012. This application is incorporated herein by reference in its entirety.The present invention is directed to improved methods of preparing certain spiro-oxindole compounds as well as various intermediates involved therein. In particular, this invention is directed to asymmetric syntheses of certain spiro-oxindole compounds, and their pharmaceutically acceptable salts, which are useful in treating sodium channel-mediated diseases or conditions, such as pain, as well as other diseases and conditions associated with the mediation of sodium channels.Sodium channels play a diverse set of roles in maintaining normal and pathological states, including the long recognized role that voltage gated sodium channels play in the generation of abnormal neuronal activity and neuropathic or pathological pain. Damage to peripheral nerves following trauma or disease can result in changes to sodium channel activity and the development of abnormal afferent activity including ectopic discharges from axotomised afferents and spontaneous activity of sensitized intact nociceptors. These changes can produce long-lasting abnormal hypersensitivity to normally innocuous stimuli, or allodynia. Examples of neuropathic pain include, but are not limited to, post-herpetic neuralgia, trigeminal neuralgia, diabetic neuropathy, chronic lower back pain, phantom limb pain, and pain resulting ...

PARASITICIDAL COMPOSITIONS COMPRISING BENZIMIDAZOLE DERIVATIVES, METHODS AND USES THEREOF

The invention relates to oral, topical or injectable compositions for combating liver fluke parasites in mammals, comprising at least one benzimidazole derivative active agent. The invention also provides for an improved method for eradicating and controlling liver fluke parasite infections and infestations in a mammal comprising administering the compositions of the invention to the mammal in need thereof. 2. A compound according to wherein Ris (C-C)-alkyl substituted with fluorine.3. A compound according to wherein Ris Cl.4. A compound according to wherein Ris a mono- or bi-halogen substituted phenyl ether.5. A compound according to wherein Ris a bi- or tri-halogen substituted phenyl.6. A compound according to or wherein the halogen is chlorine claim 1 , bromine or fluorine.7. A compound according to wherein Ris chlorine.8. A compound according to wherein Ris hydrogen.9. A compound according to that is 6-chloro-5-(4-chlorophenyl)-2-trifluoromethylbenzimidazole. (#130)10. A compound according to that is 6-chloro-5-(2 claim 1 ,3-dichlorophenoxy)-2-heptafluoropropylbenzimidazole. (#140)11. A compound according to that is 6-chloro-5-(3 claim 1 ,5-dichlorophenyl)-2-trifluoromethylbenzimidazole. (#247)12. A compound according to that is 6-chloro-5-(3 claim 1 ,4-dichlorophenyl)-2-trifluoromethylbenzimidazole. (#258)13. A compound according to that is 6-chloro-5-(2 claim 1 ,4-dichlorophenyl)-2-trifluoromethylbenzimidazole. (#260)14. A compound according to that is 6-chloro-5-(2 claim 1 ,3 claim 1 ,5-trichlorophenyl)-2-trifluoromethylbenzimidazole. (#261)15. A compound according to that is 5-chloro-6-(2 claim 1 ,4-dichlorophenoxy)-2-(heptafluoropropyl)-1H-1 claim 1 ,3-benzodiazole. (#273)16. A composition for treating helminth infestation comprising an anthelmintically effective amount of the compound of claim 1 , claim 1 , claim 1 , claim 1 , claim 1 , claim 1 , or and a pharmaceutically acceptable carrier.17. A composition for treating helminth infestation according to ...

ISOINDOLONE DERIVATIVES

The present invention provides for compounds of formula (I) 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare hydrogen; and Rand Rare each hydrogen.3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris hydrogen.4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Ris C-Calkyl.5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein Ris methyl.6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris NRR claim 5 , —NR—SO—NR—C-Calkyl claim 5 , —NR—SO—NR—C-Chaloalkyl claim 5 , —NR—SO—C-Calkyl claim 5 , —NR—SO—C-Chaloalkyl claim 5 , SO—NRR claim 5 , SO—C-Calkyl claim 5 , —C(O)—NRR claim 5 , —C(O)—NH(C-Chaloalkyl) claim 5 , —C(O)—NH(C-Calkylene-heterocycloalkyl) claim 5 , —C(O)—NH(heteroaryl) claim 5 , NH—C(O)—C-Calkyl claim 5 , or NH—C(O)-heteroaryl.7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Ris NRR claim 6 , —NRSO—C-Calkyl claim 6 , or —NH—SO—C-Chaloalkyl.8. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris heteroaryl claim 5 , 9 to 12 membered bicyclic aryl claim 5 , or napthalen-1-yl.9. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris indolyl claim 5 , 1 claim 5 ,3-benzodioxolyl claim 5 , or benzimidazolyl.10. The compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein Ris X.13. The compound of claim 12 , or a pharmaceutically acceptable salt thereof claim 12 , wherein n is 3.14. The compound of claim 12 , or a pharmaceutically acceptable salt thereof claim 12 , wherein n is 2.15. The compound of claim 14 , or a pharmaceutically acceptable salt thereof claim 14 , wherein Ris NRR claim 14 , —NR—SO—NR—C-Calkyl claim 14 , —NR—SO—NR—C-Chaloalkyl claim 14 , —NR—SO—C-Calkyl claim 14 , —NR—SO—C- ...

Asymmetric Hosts With Triaryl Silane Side Chains

Novel asymmetric host compounds containing an electron-transport moiety, a hole-transport moiety, an aromatic spacer, and a triaryl silane group are provided. These compounds are useful materials that can be incorporated into OLED devices.

2-Thiopyrimidinones

Myeloperoxidase inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, cardiovascular conditions.

MATRIX METALLOPROTEINASE INHIBITORS

The present invention relates to β-hydroxy and amino-substituted carboxylic acids, which act as matrix metalloproteinase inhibitors, particularly diastereomerically pure β-hydroxy carboxylic acids, corresponding processes for their synthesis, and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune, and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase. 2. A compound which is selected from:(2S,3R)-5-(3,3′-difluoro-4′-methoxybiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 47);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 50);(2S,3R)-5-(4′-chloro-3-fluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 56);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-β-fluoro-4′-methoxybiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 58);(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 153);(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 154);(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3- ...

Triazole Compounds that Modulate HSP90 Activity

The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a pharmaceutical composition comprising such a compound. 177-. (canceled)79. The compound of claim 78 , wherein the compound is selected from the group consisting of:5-(4-ethoxy-2-hydroxyphenyl)-4-(4-(morpholinomethyl)phenyl)-4H-1,2,4-triazole-3-carboxamide;5-(2-hydroxy-4-methoxyphenyl)-4-(4-(morpholinomethyl)phenyl)-4H-1,2,4-triazole-3-carboxamide;5-(2-hydroxy-4-prop oxyphenyl)-4-(4-(morpholinomethyl)phenyl)-4H-1,2,4-triazole-3-carboxamide;5-(2-hydroxy-4-isopropoxyphenyl)-4-(4-(morpholinomethyl)phenyl)-4H-1,2,4-triazole-3-carboxamide;5-(2,4-dimethoxyphenyl)-4-(4-(morpholinomethyl)phenyl)-4H-1,2,4-triazole-3-carboxamide;5-(2-hydroxy-4-isopropylphenyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-carboxamide;5-(2-hydroxy-4-methylphenyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-carboxamide;5-(4-hydroxy-3-isopropylphenyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-carboxamide;5-(3-tert-butyl-4-hydroxyphenyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-carboxamide;5-(4-hydroxy-3-propylphenyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-carboxamide;5-(3-cyclopentyl-4-hydroxyphenyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-carboxamide;5-(3-ethyl-4-hydroxyphenyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-carboxamide;5-(3-sec-butyl-4-hydroxyphenyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-carboxamide; and5-(3-cyclohexyl-4-hydroxyphenyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-carboxamide;or pharmaceutically acceptable salts thereof.80. The compound of claim 78 , wherein the compound is selected from the group consisting of:5-(2-hydroxy-5-isopropyl-4-methoxyphenyl)-N-isopropyl-4-( ...

Nitrogenated heterocyclic derivative, electron-transporting material for organic electroluminescent elements, and organic electroluminescent element using same

A specific nitrogen-containing heterocyclic compound having a urea structure, an electron transporting material containing the nitrogen-containing heterocyclic compound, and an organic electroluminescence device including a light emitting layer and an electron transporting layer between a cathode and an anode in which the electron transporting layer includes the electron transporting material or the nitrogen-containing heterocyclic derivative. An organic EL device exhibiting high emission efficiency even at low voltage and a material for organic EL devices are described.

C5aR ANTAGONISTS

Compounds are provided that are modulators of the C5a receptor. The compounds are substituted piperidines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activation of C5a receptors.

3-ARYLETHYNYL SUBSTITUTED QUINAZOLINONE COMPOUNDS

The present invention provides 3-arylethynyl substituted quinazolinone compounds of formula (A) as potential anticancer agents against sixty human cancer cell lines. R=H, OH, OCH; R=H, OH, CH,OCH, NO; R=H, OH, OCH, F, Cl; R+R=—OCHO—; R=H, OH, CH, OCH; R=H, OH, CH, OCH; R=H, OCH. 4. 3-Arylethynyl substituted quinazolinone compounds of general formula A as claimed in claim 1 , wherein said compounds are useful as anticancer agent.5. 3-Arylethynyl substituted quinazolinone compounds of formula 4b claim 2 , 4c claim 2 , 5d and 6l as claimed in claim 2 , wherein said compounds exhibiting an in vitro anticancer activity against sixty human cancer cell lines derived from nine cancer types leukemia cell line claim 2 , non small cell lung cell line claim 2 , colon cell line claim 2 , CNS cell line claim 2 , renal cell line claim 2 , prostate cell line claim 2 , ovarian cell line claim 2 , breast and melanoma cell line.6. 3-Arylethynyl substituted quinazolinone compounds of formula 4b claim 2 , 4c claim 2 , 5d and 6l as claimed in claim 2 , wherein said compounds exhibiting an in vitro anticancer activity against six leukemia cancer cell lines (CCRF-CEM claim 2 , HL-60 claim 2 , K-562 claim 2 , MOLT-4 claim 2 , SR and RPMI-8226) for GIare in the range of 1.66 to 3.26 claim 2 , 0.634 to 1.54 claim 2 , 2.45 to 3.85 and 0.395 to 4.66 μM claim 2 , respectively at an exposure period of at least 48 h.7. 3-Arylethynyl substituted quinazolinone compounds of formula 4b claim 2 , 4c claim 2 , 5d and 6l as claimed in claim 2 , wherein said compounds exhibiting an in vitro anticancer activity against nine non-small cell lung cancer cell lines (A549/ATCC claim 2 , EKVX claim 2 , HOP-62 claim 2 , HOP-92 claim 2 , NCI-H226 claim 2 , NCI-H23 claim 2 , NCI-H322M claim 2 , NCI-H460 and NCI-H522) for GIare in the range of 2.22 to 13.1 claim 2 , 1.24 to 1.71 claim 2 , 1.82 to 6.09 and 2.48 to 40.5 μM claim 2 , respectively claim 2 , at an exposure period of at least 48 h.8. 3-Arylethynyl ...

BENZODIOXANE INHIBITORS OF LEUKOTRIENE PRODUCTION

The present invention relates to compounds of formula (I): 120-. (canceled)21. A compound selected from the group consisting of:1-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]pyrrolidine;4-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]morpholine;1-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-4,4-dimethylpiperidine;8-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-2,8-diazaspiro[4.5]decan-1-one;1-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-4-fluoropiperidine;(1s,4s)-7-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-7-azabicyclo[2.2.1]heptane;4-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]thiomorpholine 1,1-dioxide;1-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}-N,N-dimethylpiperidine-4-carboxamide;(3S)-1-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]pyrrolidin-3-ol;1-({1-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]piperidin-3-yl}methyl)pyrrolidin-2-one;1-{4-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]piperazin-1-yl}ethanone;2-{[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]amino}-1-(pyrrolidin-1-yl)ethanone;N-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}-N-methyl-1-(methylsulfonyl)piperidin-4-amine;1-{4-[{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}(methyl)amino]piperidin-1-yl}ethanone;3-[4-(pyrrolidin-1-ylmethyl)phenyl]-2,3-dihydro[1,4]dioxino[2,3-b]pyridine;7-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine;3-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}-2,3-dihydro[1,4]dioxino[2,3-b]pyridine;3-[4-(morpholin-4-ylmethyl)phenyl]-2,3-dihydro[1,4]dioxino[2,3-b]pyridine;(3R)-1-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}piperidine-3-carboxylic acid;(3S)-1-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}piperidine-3-carboxylic acid;1-(1-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}piperidin-4-yl)-2,2,2-trifluoroethanol;2-(1-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}piperidin-4-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol;N-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-2-methylpropan-2-amine;(2R)—N-[4-(2,3-dihydro-1, ...

Aromatic heterocyclic derivative, material for organic eletroluminescent element, and organic electroluminescent element

An organic EL device includes an anode, an emitting layer, an electron transporting zone and a cathode in this sequence, in which the electron transporting zone contains an aromatic heterocyclic derivative represented by a formula (1) below. In the formula (1), X 1 to X 3 are a nitrogen atom or CR 1 , and A is represented by a formula (2) below. In the formula (2), L 1 is s single bond or a linking group, and HAr is represented by a formula (3) below. In the formula (3), Y 1 is an oxygen atom, a sulfur atom or the like, and one of X 11 to X 18 is a carbon atom bonded to L 1 by a single bond and the rest of X 11 to X 18 are a nitrogen atom or CR 13 .

B- and y -diketones and y -hydroxyketones as wnt/ b -catenin signaling pathway activators

The present invention discloses β-diketones, γ-diketones or γ-hydroxyketones or analogs thereof, that activate Wnt/β-catenin signaling and thus treat or prevent diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries related to the differentiation and development of the central nervous system, comprising Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, comprising hair loss, hematopoiesis related diseases and tissue regeneration related diseases.

NOVEL HERBICIDES

Pyrandione, thiopyrandione and cyclohexanetrione compounds, which are suitable for use as herbicides. 2. A compound according to claim 1 , wherein Ris halogen claim 1 , C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-Calkenyl or C-Calkynyl.3. A compound according to claim 1 , wherein Ris hydrogen claim 1 , which means that r is 0 claim 1 , or Ris halogen or C-Calkyl.4. A compound according to claim 1 , wherein R claim 1 , R claim 1 , Rand R claim 1 , independently of each other claim 1 , are hydrogen claim 1 , C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-CalkoxyC-Calkyl claim 1 , C-CalkylthioC-Calkyl claim 1 , C-CalkylsulfinylC-Calkyl claim 1 , C-CalkylsulfonylC-Calkyl; C-Ccycloalkyl or C-Ccycloalkyl substituted by C- or Calkyl or C- or Chaloalkyl and in which a methylene group is optionally replaced by an oxygen or sulfur atom or a sulfinyl or sulfonyl group; C-CcycloalkylC-Calkyl or C-CcycloalkylC-Calkyl substituted by C-Calkyl or C- or Chaloalkyl and in which a methylene group is optionally replaced by an oxygen or sulfur atom or a sulfinyl or sulfonyl group.5. A compound according to claim 1 , wherein R claim 1 , R claim 1 , Rand R claim 1 , independently of each other claim 1 , are hydrogen claim 1 , C-Calkyl claim 1 , C-Chaloalkyl or C-Calkoxy-C-Calkyl.6. A compound according to claim 1 , wherein Y is O claim 1 , S or C═O.7. A compound according to claim 1 , wherein{'sup': 1', '3', '4', '5', '6', '7, 'sub': 1', '4', '1', '2, 'Ris C-Calkyl; Ris hydrogen, which means that r is 0; R, R, Rand R, independently of each other, are C-Calkyl; and Y is O.'} This application is a divisional of application Ser. No. 12/519,015, which is a 371 of International Application No. PCT/EP2007/010848 filed Dec. 12, 2007, which claims priority to GB 0624961.9 filed Dec. 14, 2006, and GB 0705044.6 filed on Mar. 15, 2007, the contents of which are incorporated herein by reference.The present invention relates to novel, herbicidally active cyclic diones, and derivatives thereof, to ...

AKT INACTIVATION BY TOCOPHERYL DERIVATIVES

Anticancer compounds according to formula I are described herein. 2. The compound according to claim 1 , wherein Ris an alkyl group having from 4 to 6 carbons.3. The compound according to claim 1 , wherein Ris an alkyl claim 1 , alkenyl claim 1 , or alkaryl group having from 7 to 11 carbons.4. The compound according to claim 1 , wherein Y is an O.5. The compound according to claim 1 , wherein Rand Rare H.6. The compound according to claim 1 , wherein Ris OH.7. The compound according to claim 1 , wherein X is selected from C═O claim 1 , S═O claim 1 , and O═S═O8. The compound according to claim 7 , wherein X is C═O.9. The compound according to claim 1 , wherein Ris OH claim 1 , X is C═O claim 1 , and Y is O.12. The method of claim 11 , wherein the cancer is a cancer involving Akt signaling dysregulation.13. The method of claim 11 , wherein the cancer is prostate cancer.14. The method of claim 11 , wherein the compound is administered in a pharmaceutically acceptable carrier.15. The method according to claim 11 , wherein Rof the compound of formula I is OH.16. The method according to claim 11 , wherein X of the compound of formula I is selected from C═O claim 11 , S═O claim 11 , and O═S═O.17. The method according to claim 11 , wherein the compound of formula I is further defined such that Ris OH claim 11 , X is C═O claim 11 , and Y is O.19. The method of claim 18 , wherein Akt is inactivated while present in the membrane of the tumor cell.20. The method of claim 18 , wherein the tumor cell is in vitro. This application claims priority to U.S. Provisional Patent Application Ser. No. 61/675,964, filed Jul. 26, 2012, which is incorporated herein by reference.This invention was funded, at least in part, by National Institutes of Health Grant NIH-R01CA11250 and GRT00019777. The federal government has certain rights in this invention.Although the Selenium and Vitamin E Cancer Prevention Trial (SELECT) failed to demonstrate the chemopreventive effect of α-tocopherol in ...

IMIDAZOLE BASED LXR MODULATORS

Methods of using compounds of the invention, such as compounds of Formulae IIa, IIb, IIc, or IId 1151-. (canceled)153. The method according to claim 152 , wherein Lis a bond.155. The method according to claim 154 , wherein{'sup': '15', 'sub': 1', '2, 'each Ris independently —H or —(C-C)alkyl;'}m′ is 1 or 2; and{'sup': 5', '5a, 'Ris phenyl optionally substituted with one or more R.'}156. The method according to claim 155 , wherein{'sup': 4', '1', '1, 'claim-text': [{'sup': 15', '15, 'sub': 2', 'm, 'E is —[C(R)]—, wherein each Ris independently hydrogen or halogen; and'}, {'sup': 1', '11', '11, 'sub': 1', '6', '1', '6', '2, 'Gis —C-Calkyl, —C-Chaloalkyl, —OR, or —SOR.'}], 'each Ris independently halogen, aryl, heteroaryl, heterocyclyl, -G, or -E-G, wherein'}157. The method according to claim 155 , wherein{'sup': 41', '1', '1, 'claim-text': {'sup': 15', '15, 'sub': 2', 'm, 'E is —[C(R)]—, wherein each Ris independently hydrogen or halogen; and'}, 'each Ris independently halogen, -G, or -E-G, wherein'}{'sup': '1', 'sub': 1', '6', '1', '6, 'Gis —C-Calkyl or —C-Chaloalkyl.'}158. The method according to claim 154 , wherein{'sup': '15', 'Ris H;'}m is 1, 2, or 3; and{'sup': 5', '5a, 'Ris heterocyclyl optionally substituted with one or more R.'}159. The method according to claim 158 , wherein{'sup': 4', '1', '1, 'claim-text': [{'sup': 15', '15, 'sub': 2', 'm, 'E is —[C(R)]—, wherein each Ris independently hydrogen or halogen; and'}, {'sup': 1', '11', '11, 'sub': 1', '6', '1', '6', '2, 'Gis —C-Calkyl, —C-Chaloalkyl, —OR, or —SOR.'}], 'each Ris independently halogen, aryl, heteroaryl, heterocyclyl, -G, or -E-G, wherein'}160. The method according to claim 158 , wherein{'sup': 41', '1', '1, 'claim-text': [{'sup': 15', '15, 'sub': 2', 'm, 'E is —[C(R)], wherein each Ris independently hydrogen or halogen; and'}, {'sup': '1', 'sub': 1', '6', '1', '6, 'Gis —C-Calkyl or —C-Chaloalkyl.'}], 'each Ris independently halogen, -G, or -E-G, wherein'}161. The method according to claim 154 , ...

Prolyl hydroxylase inhibitors and methods of use

The present disclosure relates to HIF-1α prolyl hydroxylase inhibitors, compositions which comprise the HIF-1α prolyl hydroxylase inhibitors described herein and to methods for controlling, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, and anemia.

NOVEL DIPHENYLMETHANE DERIVATIVES AS SGLT2 INHIBITORS

The present invention relates to a compound with a diphenylmethane moiety having an inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) being present in the intestine and kidney, and a pharmaceutical composition comprising the same as an active ingredient, which is useful for preventing or treating metabolic disorders, particularly diabetes. The present invention also provides a method for preparing the compound, and a method for preventing or treating metabolic disorders, particularly diabetes, by using the compound. 5. The compound of , wherein said ring A is a benzene , indane , indene , dihydrobenzofuran , dihydroisobenzofuran , benzofuran , dihydrobenzothiophene , benzothiophene , tetrahydronaphthalene , dihydronaphthalene , chroman , chromene , isochroman , isochromene , benzodioxole , benzodioxane , benzooxazine , tetrahydroquinoline , tetrahydroquinoxaline , tetrahydroisoquinoline , indazole , indole , indoline , benzoimidazole , benzooxazole , benzothiazole , benzotriazole , quinazoline , quinoxaline , cinnoline , phthalazine , or benzotriazine ring , which is optionally substituted with a substituent as defined in .6. The compound of , wherein said ring B is a quinoline , quinoxaline , 3 ,4-dihydro-2H-benzo[b][1 ,4]dioxepine , 2 ,3-dihydrobenzo[b]thiophene , indazole , indole , 2 ,3-dihydrobenzo[b][1 ,4]dioxine , benzodioxole , indane , tetrahydronaphthalene , 3 ,4-dihydro-2H-thiochromene , dihydrobenzofuran , benzo[d][1 ,3]oxathiole , tetrahydroquinoline , or 3 ,4-dihydro-2H-benzo[b][1 ,4]oxazine ring , which is optionally substituted with a substituent as defined in .7. The compound of claim 1 , which is selected from the group consisting of:(1) (2S,3R,4R,5S,6R)-2-(7-bromo-6-(4-methoxybenzyl)-2,3-dihydro-1H-inden-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;(2) (2S,3R,4R,5S,6R)-2-(7-bromo-6-(4-ethoxybenzyl)-2,3-dihydro-1H-inden-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;(3) (2S,3R,4R,5S,6R)-2-(7-bromo-6-(4- ...

Monomer for hardmask composition and hardmask composition including the monomer and method of forming patterns using the hardmask composition

A monomer for a hardmask composition is represented by the following Chemical Formula 1,

PIPERIDINE AND PIPERAZINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS AND CANCER

Disclosed are compounds of formula (I) (formula I), as antiviral agents, antineoplastic agents, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X and Y are independently CH or N, o is 0, 1 or 2, and E is absent or is (CRR)m, NH, or S, F is absent or is (CRR)n, C=O, or —SO—, G is absent or is (CRCR)r, H is absent or is C═O, or —SO2- and R, Ar, Arare as defined in the specification. These compounds are antiviral agents and are contemplated in the treatment of viral infections, for example, hepatitis C, or are antineoplastic agents. 2. The compound claim 1 , salt claim 1 , stereoisomers claim 1 , and mixtures comprising stereoisomers of claim 1 , wherein X is CH and Y is N and 0 is 1.3. (canceled)4. The compound claim 1 , salt claim 1 , stereoisomers claim 1 , and mixtures comprising stereoisomers of claim 1 , wherein E is (CRR) claim 1 , F is absent claim 1 , and m is 2 claim 1 , and H is absent and r is 1.5. (canceled)6. (canceled)7. The compound claim 1 , salt claim 1 , stereoisomers claim 1 , and mixtures comprising stereoisomers of claim 1 , wherein Ris selected from C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , and C-Ccycloalkyl C-Calkyl.8. The compound claim 1 , salt claim 1 , stereoisomers claim 1 , and mixtures comprising stereoisomers of claim 1 , wherein Ris selected from hydrogen claim 1 , cyclopentyl claim 1 , sec-butyl claim 1 , isopropyl claim 1 , cyclohexyl claim 1 , n-propyl claim 1 , n-butyl claim 1 , benzoyl claim 1 , methyl claim 1 , ethyl claim 1 , trideuteromethyl claim 1 , 2 claim 1 ,2 claim 1 ,2-trideuteroethyl claim 1 , 2 claim 1 ,2 claim 1 ,2-trifluoroethyl claim 1 , phenylsulfonyl claim 1 , and benzyl.9. The compound claim 1 , salt claim 1 , stereoisomers claim 1 , and mixtures comprising stereoisomers of claim 1 , wherein Ris selected from Caryl and C-Caryl C-Calkyl claim 1 , wherein the aryl is optionally substituted with one or more substituents selected from halo claim 1 , cyano claim 1 ...

ANTIDIABETIC BICYCLIC COMPOUNDS

Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia. 2. The compound according to wherein “a” is a single bond; or a pharmaceutically acceptable salt thereof.3. The compound according to wherein T is CH; U is CR; V is CR; and W is CH claim 1 , N or N-oxide; or a pharmaceutically acceptable salt thereof.4. The compound according to wherein T is CH; U is CR; V is CR; and W is CH; or a pharmaceutically acceptable salt thereof.5. The compound according to wherein T is CH; U is CR; V is CR; and W is N; or a pharmaceutically acceptable salt thereof.6. The compound according to wherein Y is selected from the group consisting of:{'sup': g', 'g, '(1) —CRR,'}(2) C═O,{'sup': 'g', 'sub': '1-6', '(3) —C(R)OCalkyl,'}{'sub': '2', '(4) —CF, and'}{'sup': 'c', '(5) —NR;'}or a pharmaceutically acceptable salt thereof.7. The compound according to wherein Y is selected from the group consisting of: —CRR; or a pharmaceutically acceptable salt thereof.8. The compound according to wherein A is selected from the group consisting of:(1) aryl, and(2) heteroaryl,{'sup': 'a', 'wherein each aryl and heteroaryl is unsubstituted or substituted with one to five substituents selected from R; or a pharmaceutically acceptable salt thereof.'}9. The compound according to wherein B is selected from the group consisting of:(1) hydrogen,(2) aryl,(3) aryl-O—,{'sub': '1-10', '(4) aryl-Calkyl-O—'}{'sub': '3-6', '(5) Ccycloalkenyl, and'}(6) heteroaryl,{'sup': 'b', 'wherein B is unsubstituted or ...

Derivatives of Xanthone Compounds

The present invention relates to xanthone analogs. Such compounds may be used in the treatment of bacterial infections. 136.-. (canceled)40. The compound of claim 39 , wherein each occurrence of Rin Formula (IIa-2) is independently optionally substituted alkyl.41. The compound of claim 40 , wherein Rindependently for each occurrence is —N(H)(C═NH)NH.42. The compound of claim 37 , wherein Ris hydrogen claim 37 , and Ris alkyl.46. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 37 , or a pharmaceutically acceptable salt thereof claim 37 , and a pharmaceutically acceptable excipient.47. The pharmaceutical composition of claim 46 , further comprising one or more additional therapeutic agents.48. A method for treating a microbial infection in a patient in need thereof claim 37 , the method comprising administering to the patient a therapeutically effective amount of a compound according to claim 37 , or a pharmaceutically acceptable salt thereof.49. The method of claim 48 , wherein the microbial infection is a Gram negative bacterial infection or a Gram positive bacterial infection.50StreptococcusStaphylococcusBacillusCarynebacteriumClostridiumListeriaEnterococcus. The method of claim 49 , wherein the Gram positive bacteria is selected from the group consisting of spp. claim 49 , spp. claim 49 , spp. claim 49 , spp. claim 49 , spp. claim 49 , spp. claim 49 , and spp.51Staphylococcus aureus.. The method of claim 50 , wherein the Gram positive bacteria is52Staphylococcus aureusStaphylococcus aureus.. The method of claim 51 , wherein the is Methicillin resistant53. The method of claim 48 , the method further comprising administering one or more additional therapeutic agents.55. The compound of claim 54 , wherein Ris hydrogen claim 54 , and Ris alkyl.60. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 54 , or a pharmaceutically acceptable salt thereof claim ...

GRISEOFULVIN COMPOUND

An object of the present invention is to provide a compound having an anti-inflammatory activity or a pharmacologically acceptable salt thereof. 116-. (canceled)17. A pharmaceutical composition comprising a compound or a pharmacologically acceptable salt thereof selected from the following group as an active ingredient:(2S,5′R)-7-chloro-6-(2-hydroxyethoxy)-3′,4-dimethoxy-5′-methyl-spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-3′,4-dimethoxy-6-(2-methoxyethoxy)-5′-methyl-spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-3′,4-dimethoxy-5′-methyl-6-(1-methylpyrazol-3-yl)spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-6-(1-ethylpyrazol-3-yl)-3′,4-dimethoxy-5′-methyl-spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-3′,4-dimethoxy-5′-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-3′,4-dimethoxy-5′-methyl-6-(3-methyl-1,2,4-oxadiazol-5-yl)spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-3′,4-dimethoxy-5′-methyl-6-(5-methyl-1,2,4-oxadiazol-3-yl)spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-6-[5-(1-hydroxy-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-3′,4-dimethoxy-5′-methyl-spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-6-[5-[(1S)-1-hydroxyethyl]-1,3,4-oxadiazol-2-yl]-3′,4-dimethoxy-5′-methyl-spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-6-[5-[(1R)-1-hydroxyethyl]-1,3,4-oxadiazol-2-yl]-3′,4-dimethoxy-5′-methyl-spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-4-ethoxy-6-[5-(1-hydroxy-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-3′-methoxy-5′-methyl-spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-4-ethoxy-6-[5-[(1S)-1-hydroxyethyl]-1,3,4-oxadiazol-2-yl]-3′-methoxy-5′-methyl-spiro[benzofuran-2,4′-cyclohex-2-ene]-1′,3-dione,(2S,5′R)-7-chloro-6-[3-(1-hydroxyethyl)-1,2,4-oxadiazol-5-yl]-3′,4-dimethoxy-5′-methyl-spiro[benzofuran-2,4′-cyclohex-2-ene ...

PYRAZOLE DERIVATIVES AS INHIBITORS OF THE WNT SIGNALLING PATHWAY

The present invention relates to a novel class of compounds as inhibitors of the Wnt signalling pathway. The best compounds showed potencies in the low micromolar range and high efficacies (>80%) together with good microsomal stability. Furthermore, in vitro characterization of the compounds show promising effects in various anti-cancer assays. Finally, in vivo characterization showed high accumulation in breast tissue. 216-. (canceled)17. The method according to claim 1 , wherein said optionally substituted aryl is selected from a 6- claim 1 , or 10-membered aryl.18. The method according to claim 1 , wherein said optionally substituted heteroaryl is selected from a 5- claim 1 , 6- claim 1 , 9- or 10-membered heteroaryl claim 1 , wherein the number of heteroatoms is 1-3 claim 1 , and wherein said heteroatoms are independently selected from the group consisting of N claim 1 , S claim 1 , and O.19. The method according to claim 1 , wherein said aryl and heteroaryl are be substituted with one or more substituents claim 1 , which may be the same or different claim 1 , and are independently selected from the group consisting of C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , phenyl claim 1 , amino (—NH) claim 1 , azido (—N) claim 1 , azo C-Calkyl (—N-alkyl) claim 1 , cyanato (—OCN) claim 1 , isocyanato (—NCO) claim 1 , nitroxy (—ONO) claim 1 , —CHNH(C-Calkyl) claim 1 , —CHN(C-Calkyl) claim 1 , aminoalkyl (—NH(C-Calkyl) claim 1 , —N(C-Calkyl) claim 1 , (—N(C-Calkyl)) claim 1 , 1 claim 1 ,3- or 1 claim 1 ,4-dioxyl claim 1 , morpholyl claim 1 , cyano (—CN) claim 1 , isocyano (—NC) claim 1 , nitroso (—NO) claim 1 , CONH claim 1 , CONH(C-Calkyl) claim 1 , CON(C-Calkyl) claim 1 , hydroxyl (—OH) claim 1 , hydroperoxy (—OOH) claim 1 , C-Cperoxy alkyl (—OO-alkyl) claim 1 , C-Calkyl hydroxyl (-alkyl-OH) claim 1 , C-Calkoxy (—O-alkyl) claim 1 , carboxylic acid (—COOH) claim 1 , C-Calkyl esters (—COO-alkyl) claim 1 , oxetanyl claim 1 , C-Calkyl acyl (—CO-alkyl) claim 1 ...

Novel Polycyclic Compound

Novel polycyclic compounds, synthesis methods and applications thereof are provided. The compound comprise a plurality of carbocyclic and/or heterocyclic structures having at least one group that emits visible light or fluorescence and at least one ultraviolet and/or visible (blue) light absorbing group covalently bonded to provide stability. The compounds can be used as a light conversion agent, dye, pigment, fluorescence agent, ultraviolet light or blue light absorber, and is applied to optical film, agricultural film, optical disk (disc), optical lens, goggles, skin care, makeup, lighting, coatings, adhesives, light stabilizers, or panels. 1. A novel type of polycyclic compound , a structure of the compound is represented by formula (1) or formula (2) ,{'br': None, 'sub': 1', '2', '3, 'A-R—B—R—C—R-D\u2003\u2003 (1),'}{'br': None, 'sub': 1', '2', '3, 'A-R—B—R-D-R—C\u2003\u2003 (2),'}{'sub': 2', '2', '3', '1, 'sup': '3', 'including at least one visible light or fluorescence emitting group, and at least an additional ultraviolet light absorbing group, wherein the visible light or fluorescence emitting group is R—C—R-D or R-D-R—C; the ultraviolet light absorbing group is A-R—B;'}{'sub': 1', '3, 'Rto Rare each independently a bond or/and any divalent linking group;'}{'sub': '4', 'A, B, and C are each independently a benzene ring, a benzo-carbocyclic ring, a nitrogen-containing 5˜7 membered heterocyclic ring, or a nitrogen-containing 5˜7 membered benzo-heterocyclic ring, which substituted by R;'}{'sub': 1', '8', '4', '1', '8, 'D is a substituted 5˜7 membered heterocyclic ring or a 5˜7 membered benzo-heterocyclic ring composed of carbon, nitrogen, oxygen, and sulfur atoms, wherein, each substituent of the ring on carbon atom is selected from the group consisting of hydrogen, hydroxyl, oxo, thio, thiol, amine, imino, C˜Clinear or branched alkyl or alkenyl, and R, and the substituent of the ring on nitrogen atom is selected from the group consisting of hydrogen, hydroxyl, ...

Novel compound, material for organic electroluminescence device, and organic electroluminescence device

A compound represented by the following formula (1):

TETRAHYDROISOQUINOLINES AS SELECTIVE NADPH OXIDASE 2 INHIBITORS

Embodiments of bridged tetrahydroisoquinolines and methods for their use in selectively inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 are disclosed. The disclosed compounds have a structure according to general formula I or a pharmaceutically acceptable salt thereof: 2. The method of claim 1 , wherein Ris Calkyl claim 1 , substituted or unsubstituted aryl claim 1 , or substituted or unsubstituted heteroaryl.3. The method of claim 2 , wherein:{'sup': '1', 'Ris hydrogen, halogen, or substituted or unsubstituted aryl;'}{'sup': '4', 'Ris lower alkyl, or substituted or unsubstituted aryl; and'}{'sup': '5', 'Ris hydrogen or halogen.'}4. The method of claim 3 , wherein Ris halogen.5. The method of claim 3 , wherein Ris bromo.6. The method of claim 1 , wherein Ris —CHRand Ris Calkyl claim 1 , substituted or unsubstituted Caryl claim 1 , or substituted or unsubstituted C-Cheteroaryl.9. The method of claim 1 , wherein the condition is a cardiovascular disease claim 1 , a neurodegenerative disease claim 1 , or cancer.10. The method of claim 9 , wherein the cardiovascular disease is atherosclerosis claim 9 , hypertension claim 9 , ischemia reperfusion claim 9 , cardiac hypertrophy claim 9 , cardiomyopathy claim 9 , stroke claim 9 , restenosis claim 9 , or any combination thereof.11. The method of claim 9 , wherein the cardiovascular disease is atherosclerosis.12. The method of claim 9 , wherein the neurodegenerative disease is Huntington's disease claim 9 , Alzheimer's disease claim 9 , Parkinson's disease claim 9 , or any combination thereof.13. The method of claim 1 , further comprising identifying the subject as having claim 1 , suspected of having claim 1 , or at risk of developing a condition mediated by Nox2 and/or reactive oxygen species produced by Nox2 activity by diagnosing the subject with a cardiovascular disease claim 1 , a neurodegenerative disease claim 1 , or cancer claim 1 , or determining that the subject has one or more risk factors ...

Pharmaceutically Active Compounds

The invention is directed to compounds of general formula (I) 2464.-. (canceled)466. The method according to claim 465 , wherein one or both of Rand Rrepresents a protecting group.467. The method according to claim 465 , which is carried out in the presence of a coupling agent.469481.-. (canceled)483. A method according claim 482 , wherein Rrepresents a six-membered aliphatic carbocyclic ring claim 482 , optionally substituted by —(C═O)NRR claim 482 , —OR claim 482 , —SOR or Calkyl.484. A method according to claim 483 , wherein Rrepresents a six-membered aliphatic carbocyclic ring claim 483 , optionally substituted by —(C═O)NRRor —OR.485. A method according to claim 483 , wherein Rrepresents a six-membered aliphatic carbocyclic ring claim 483 , optionally substituted by —(C═O)NRR.486. A method according to claim 482 , wherein Rand/or Rrepresent:{'sub': 1-6', '3, '(a) Calkyl optionally substituted by —OCH; or'}{'sub': '1-6', '(b) cyclopropyl or cyclobutyl, any of which is optionally substituted by Calkyl; or'}{'sub': '1-6', '(c) a 4-membered heterocycloalkyl ring, optionally substituted by Calkyl; or'}{'sup': 'd', '(d) —(C═O)R; or'}{'sub': '2', 'sup': 'e', '(e) —SOR.'}487. A method according to claim 482 , wherein Rand/or Rrepresent:{'sub': 3', '2', '3', '2', '3', '3', '3', '2', '3', '3', '3', '2', '2', '3', '2', '2', '3', '1-6, '(a) —CH, —CHF, —C(CH)CF, —C(CH), —CHC(CH), —CH(CH), —CHCHor —CHCHCH; or Calkyl optionally substituted by cycloalkyl, halo or alkoxy; or'}{'sub': '1-6', '(b) Calkyl optionally substituted by cyclopropyl or cyclobutyl; or'}{'sub': 3', '2', '3, '(c) —OCHor —OCHCH; or'}{'sub': 3-6', '1-6, '(d) Ccycloalkyl optionally substituted by Calkyl.'} This application is a divisional of U.S. patent application Ser. No. 15/533,048, filed Jun. 5, 2017, which is a national phase entry pursuant to 35 U.S.C. § 371 of International Application No. PCT/EP2015/081168, filed Dec. 23, 2015, which claims the benefit of priority of Application No. GB 1423087.4, filed ...

ORGANIC ELECTROLUMINESCENT MATERIALS AND DEVICES

The present application includes novel compounds containing xanthene and spiro dixanthene ring structures. These compounds are useful as host materials with high triplet energies for phosphorescent electroluminescent devices. 2. The compound of claim 1 , wherein at least one of Land Lis a direct bond.3. The compound of claim 1 , wherein Land Lare each a direct bond.4. The compound of claim 1 , wherein Lis a silyl group.9. The OLED of claim 8 , wherein the organic layer is an emissive layer and the compound of Formula I is a host.11. The OLED of claim 8 , wherein the organic layer is a blocking layer and the compound of Formula I is a blocking material in the organic layer.12. The OLED of claim 8 , wherein the organic layer is a transporting layer and the compound of Formula I is a transporting material in the organic layer.13. The OLED of claim 8 , wherein the organic layer is an emissive layer and the compound of Formula I is an emitter.14. The OLED of claim 13 , wherein the OLED emits a luminescent radiation at room temperature when a voltage is applied across the organic light emitting device claim 13 , and wherein the luminescent radiation comprises a delayed fluorescence process.15. The OLED of claim 13 , wherein the emissive layer further comprises a host material.16. The OLED of claim 13 , wherein the emissive layer further comprises a first phosphorescent emitting material.17. The OLED of claim 16 , wherein the emissive layer further comprises a second phosphorescent emitting material.18. The OLED of claim 16 , wherein the OLED emits a white light at room temperature when a voltage is applied across the organic light emitting device.20. The consumer product of claim 19 , wherein the consumer product is selected from the group consisting of a flat panel display claim 19 , a computer monitor claim 19 , a medical monitor claim 19 , a television claim 19 , a billboard claim 19 , a light for interior or exterior illumination and/or signaling claim 19 , a heads-up ...

CONDENSED CYCLIC COMPOUND AND ORGANIC LIGHT-EMITTING DEVICE INCLUDING THE SAME

Provided are a condensed cyclic compound having the following structure: 2. The condensed cyclic compound of claim 1 , wherein ring Dand ring Dare each independently selected from a benzene claim 1 , a naphthalene claim 1 , an anthracene claim 1 , a phenanthrene claim 1 , a chrysene claim 1 , and a pyrene.3. The condensed cyclic compound of claim 1 , wherein Lis selected from:a phenylene group, a pentalenylene group, an indenylene group, a naphthylene group, an azulenylene group, a heptalenylene group, an indacenylene group, an acenaphthylene group, a fluorenylene group, a spiro-bifluorenylene group, a benzofluorenylene group, a dibenzofluorenylene group, a phenalenylene group, a phenanthrenylene group, an anthracenylene group, a fluoranthenylene group, a triphenylenylene group, a pyrenylene group, a chrysenylene group, a naphthacenylene group, a picenylene group, a perylenylene group, a pentaphenylene group, a hexacenylene group, a pentacenylene group, a rubicenylene group, a coronenylene group, a ovalenylene group, a pyrrolylene group, a thiophenylene group, a furanylene group, an imidazolylene group, a pyrazolylene group, a thiazolylene group, an isothiazolylene group, an oxazolylene group, an isoxazolylene group, a pyridinylene group, a pyrazinylene group, a pyrimidinylene group, a pyridazinylene group, an isoindolylene group, an indolylene group, an indazolylene group, a purinylene group, a quinolinylene group, an isoquinolinylene group, a benzoquinolinylene group, a phthalazinylene group, a naphthyridinylene group, a quinoxalinylene group, a quinazolinylene group, a cinnolinylene group, a phenanthridinylene group, an acridinylene group, a phenanthrolinylene group, a phenazinylene group, a benzimidazolylene group, a benzofuranylene group, a benzothiophenylene group, an isobenzothiazolylene group, a benzoxazolylene group, an isobenzoxazolylene group, a triazolylene group, a tetrazolylene group, an oxadiazolylene group, a triazinylene group, a dibenzofuranylene ...

NITROGENATED AROMATIC HETEROCYCLIC DERIVATIVE AND ORGANIC ELECTROLUMINESCENT ELEMENT USING SAME

A nitrogen-containing aromatic heterocyclic derivative in which a nitrogen atom of an indenocarbazole skeleton optionally having a hetero atom or an indenoindole skeleton optionally having a hetero atom is bonded to a dibenzofuran or a dibenzothiophene directly or indirectly. The derivative realizes an organic EL device with a high emission efficiency and a long lifetime. 2: The aromatic heterocyclic derivative according to claim 1 , whereinW of formulae (1-1) and (1-2) represents a single bond, andZ of formulae (1a) and (1b) represents a single bond.7: The aromatic heterocyclic derivative according to claim 1 , wherein Lrepresents a single bond.9. (canceled)10: The aromatic heterocyclic derivative according to claim 1 , wherein X represents an oxygen atom.11: The aromatic heterocyclic derivative according to claim 1 , wherein X represents a sulfur atom.12: The aromatic heterocyclic derivative according to claim 1 , wherein X represents CRR.13: The aromatic heterocyclic derivative according to claim 1 , wherein X represents SiRR.14: The aromatic heterocyclic derivative according to claim 1 , wherein Y represents an oxygen atom.15: The aromatic heterocyclic derivative according to claim 1 , wherein Y represents a sulfur atom.16: The aromatic heterocyclic derivative according to claim 1 , wherein Lis bonded to a carbon atom at 4-position of the structure represented by formula (1c).17. A material for organic electroluminescence device claim 1 , comprising the aromatic heterocyclic derivative according to .18: A hole transporting material for organic electroluminescence device claim 1 , comprising the aromatic heterocyclic derivative according to .19: An organic electroluminescence device claim 1 , comprising:a light emitting layer, andorganic thin film layers between an anode and a cathode,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein at least one of the organic thin film layers comprises the aromatic heterocyclic derivative according to .'}20: The ...

COMPOUND FOR ORGANIC-ELECTRIC ELEMENT, ORGANIC-ELECTRIC ELEMENT USING SAME, AND ELECTRONIC DEVICE FOR SAME

The present invention provides the compound represented by Formula 1, an organic electric element comprising a first electrode, a second electrode, and an organic material layer formed between the first electrode and the second electrode, and electronic device thereof, and by comprising the compound represented by Formula 1 in the organic material layer, the driving voltage of the organic electronic device can be lowered, and the luminous efficiency and life time of the organic electronic device can be improved. 5. An organic electric element comprising a first electrode claim 1 , a second electrode claim 1 , and an organic material layer formed between the first electrode and the second electrode claim 1 , wherein the organic material layer comprises the compound of .6. The organic electric element of claim 5 , wherein the compound is comprised in at least one layer of a hole injection layer claim 5 , a hole transport layer claim 5 , an emission-auxiliary layer claim 5 , a light emitting layer claim 5 , an electron transport-auxiliary layer and an electron transport layer claim 5 , and the compound is comprised as a single compound or a mixture of two or more different kinds.7. The organic electric element of claim 5 , further comprising a layer for improving luminous efficiency formed on one side of the first electrode and/or one side of the second electrode claim 5 , the side not facing the organic material layer.8. The organic electric element of claim 5 , wherein the organic material layer is formed by any one of the processes of spin coating claim 5 , nozzle printing claim 5 , inkjet printing claim 5 , slot coating claim 5 , dip coating and roll-to-roll.9. An electronic device comprising a display device and a control unit for driving the display device claim 5 , wherein the display device comprises the organic electric element of .10. The electronic device of claim 9 , wherein the organic electric element is an organic light emitting diode claim 9 , an ...

Poly-adp ribose polymerase (parp) inhibitors

The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula:The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.

METABOTROPIC GLUTAMATE RECEPTOR NEGATIVE ALLOSTERIC MODULATORS (NAMS) AND USES THEREOF

Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor negative allosteric modulators (NAMs), compositions comprising the compounds, and methods of using the compounds and compositions. 162.-. (canceled)65. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein X is —O—.66. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein Ris substituted or unsubstituted heteroaryl.67. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein n is 1 and Ris halogen or —CH.68. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein Ris —CF.69. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein m is 0.71. A pharmaceutical composition comprising a compound of claim 63 , or a pharmaceutically acceptable salt claim 63 , and at least one pharmaceutically acceptable excipient.72. A method of treating a central nervous disorder (CNS) claim 63 , the method comprising the step of administering to a subject in need thereof claim 63 , an effective amount of a compound of claim 63 , thereby treating the disorder.75. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein X is —O—.76. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein Ris substituted or unsubstituted heteroaryl.77. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein n is 1 and Ris halogen or —CH.78. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein Ris —CF.79. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein m is 0.81. A pharmaceutical composition comprising a compound of claim 73 , or a pharmaceutically acceptable salt claim 73 , and at least one pharmaceutically acceptable excipient.82. A method of treating ...