ИНГИБИТОРЫ КРУЗИПАИНА И ДРУГИХ ЦИСТЕИНПРОТЕАЗ

Изобретение относится к соединению в соответствии с общей формулой (I) или общей формулой (II) где R1=Н; Z=О или S; Р1=CR5R6, Р2=CR7R8, Q=CR9R10; каждый из R5, R6, R7, R8, R9 и R10 означает Н; Y=CR12R13-CO, где R12, R13 выбирают из С0-7-алкила, С3-6 -циклоалкила или фенил-С0-7-алкила; и где фенильное кольцо необязательно замещено R19, имеющим значения, указанные ниже; в группе (Х)о, Х=CR14R15, где R14 и R15 независимо выбирают из С0-7-алкила, и о представляет собой число от нуля до трех; (W)n, W=О, S, С(O), S(O) или S(O)2 или NR16, где R16 означает H, и n равен нулю или единице; (V)m, V-С(O), NHC(O), C(O)NH или CR17R18, где R17 и R18 означает Н, и m представляет собой число от нуля до трех, при условии, что когда m больше единицы, (V)m содержит максимум одну карбонильную группу; U = стабильное 5-7-членное моноциклическое или 8-11-членное бициклическое кольцо, которое является насыщенным или ненасыщенным и которое включает от нуля до четырех гетероатомов, выбранное из: где R19 представляет ...

СОЕДИНЕНИЯ ДЛЯ ОРГАНИЧЕСКИХ ЭЛЕКТРОННЫХ УСТРОЙСТВ

Изобретение относится к органическим электролюминесцентным устройствам на основе соединений формулы (1) ! ! где Y, Z выбраны из N, P, P=O, C=O, O, S, S=O и SO2; Ar1, Ar2, Ar3 выбраны из бензола, нафталина, антрацена, фенантрена, пиридина, пирена или тиофена, необязательно замещенных R1; Ar4, Ar5, Ar6, Ar7 выбраны из бензола, нафталина, антрацена, фенантрена, пиридина, пирена, тиофена, трифениламина, дифенил-1-нафтиламина, дифенил-2-нафтиламина, фенилди(1-нафтил)амина, фенилди(2-нафтил)амина или спиробифлуорена, необязательно замещенных R1; Е - одинарная связь, N(R1), О, S или C(R1)2; R1 представляет собой Н, F, CN, алкил, где СН2 группы могут быть заменены на -R2C=CR2-, -C≡C-, -О- или -S-, и Н может быть заменен на F, необязательно замещенные арил или гетероарил, где R1 могут образовывать кольцо друг с другом; R2 - Н, алифатический или ароматический углеводород; X1, X4, X2, X3 - выбраны из C(R1)2, C=O, C=NR1, О, S, S=O, SO2, N(R1), P(R1), P(=O)R1, C(R1)2-C(R1)2, C(R1)2-C(R1)2-C(R1)2, C( ...

АЗЕТИДИНИЛДИАМИДЫ В КАЧЕСТВЕ ИНГИБИТОРОВ МОНОАЦИЛГЛИЦЕРИН-ЛИПАЗЫ

Изобретение относится к соединениям формулы (I), где Y и Z независимо выбраны из группы а) или b) таким образом, что один из Y или Z выбран из группы а), а другой - из группы b); группа а) представляет собой i) замещенный Cарил; ii) Cциклоалкил, необязательно замещенный одним или двумя заместителями, представляющими собой фтор; iii) трифторметил; или iv) гетероарил, выбранный из группы, состоящей из тиенила, фуранила, тиазолила, изотиазолила, оксазолила, пирролила, пиримидинила, изоксазолила, бензотиенила, тиено[3,2-b]тиофен-2-ила, пиразолила, триазолила и [1,2,3]тиадиазолила; где Cарил замещен, а гетероарил необязательно замещен одним заместителем, выбранным из группы, состоящей из фтора, хлора, брома, Cалкила, Cалкокси и Cалкилкарбониламино; группа b) представляет собой i) Cарил; ii) гетероарил, выбранный из группы, состоящей из тиазолила, пиридинила, индолила, индазолила, бензоксазолила, бензотиазолила, бензофуранила, бензотиенила, 1Н-пирроло[3,2-b]пиридин-5-ила, 1Н-тиено[2,3-c]пиразол ...

ПРОИЗВОДНОЕ ПИПЕРИДИНА, СПОСОБ ЕГО ПОЛУЧЕНИЯ И ЕГО ФАРМАЦЕВТИЧЕСКОЕ ПРИМЕНЕНИЕ

Изобретение относится к области органической химии, а именно к гетероциклическому соединению формулы (I), к его энантиомеру или к его фармацевтически приемлемой соли, где кольцо А выбрано из группы, состоящей из структур, указанных в формуле изобретения; R представляет собой атом водорода; каждый Rидентичен другому или отличен от него и каждый выбран из атома водорода и атома галогена; Rвыбран из С-алкила и С-циклоалкила, где каждый указанный С-алкил необязательно замещен 1 группой, выбранной из атома галогена; Rвыбран из С-алкила; каждый Rидентичен другому или отличен от него и каждый независимо выбран из атома водорода, С-циклоалкила, атома галогена, циано, С-алкинила, гетероциклила, С-арила, гетероарила, -OR, -NHC(O)ORи -NHC(O)NRR, где каждый указанный С-алкинил, гетероциклил, С-арил и гетероарил необязательно замещен 1-2 группами, выбранными из R, С-алкила, галоген-С-алкила, гидрокси-С-алкила, амино, оксо, С-циклоалкила или гетероциклила; Rпредставляет собой гетероарил, где указанный ...

ДИФТОРМЕТИЛАМИНОПИРИДИНЫ И ДИФТОРМЕТИЛАМИНОПИРИМИДИНЫ

Изобретение относится к соединениям формулы (I), где X1, X2 и X3 представляют собой, независимо друг от друга, N или CH, при условии, что по меньшей мере два из X1, X2 и X3 представляют собой N; Y представляет собой N или CH; R1 и R2 независимо друг от друга представляют собой (i) морфолинил формулы (II) (II), где стрелка обозначает связь в формуле (I); и где R3 и R4 независимо друг от друга представляют собой H, C1-C3алкил, необязательно замещенный одной или двумя группами OH, C1-C2фторалкил, C1-C2алкокси, C1-C2алкокси-C1-C3алкил, CN или C(O)O-C1-C2алкил; или R3 и R4 вместе образуют двухвалентный остаток -R5R6-, выбранный из C1-C3алкилена, необязательно замещенного 1 - 4 атомами F, -CH2-O-CH2-, -CH2-NH-CH2- или любой из структур , где стрелки обозначают связи в формуле (II);(ii) насыщенное 5-6-членное гетероциклическое кольцо Z, содержащее от 1 до 2 гетероатомов, независимо выбранных из N, O и S, необязательно содержащее от 1 до 3 заместителей R9; причем R9 независимо в каждом случае представляет ...

АЗЕТИДИНИЛДИАМИДЫ В КАЧЕСТВЕ ИНГИБИТОРОВ МОНОАЦИЛГЛИЦЕРИН-ЛИПАЗЫ

Изобретение относится к соединению формулы (I)где Y и Z независимо выбраны из группы а) или b) таким образом, что один из Y или Z выбран из группы а), а другой - из группы b); группа а) представляет собой i) замещенный Сарил; ii) Сциклоалкил; iii) трифторметил или iv) гетероарил, выбранный из группы, состоящей из тиенила, фуранила, тиазолила, изотиазолила, оксазолила, пирролила, пиридинила, изоксазолила, имидазолила, фуразан-3-ила, бензотиенила, тиено[3,2-b]тиофен-2-ила, пиразолила, триазолила, тетразолила и [1,2,3]тиадиазолила; группа b) представляет собой i) Сарил; ii) гетероарил, выбранный из группы, состоящей из тиазолила, пиридинила, индолила, пирролила, бензоксазолила, бензотиазолила, бензотиенила, бензофуранила, имидазо[1,2-а]пиридин-2-ила, фуро[2,3-b]пиридинила, пирроло[2,3-b]пиридинила, пирроло [3,2-b]пиридинила, тиено[2,3-b]пиридинила, хинолинила, хиназолинила, тиенила и бензимидазолила; iii) бензоконденсированный гетероциклил, присоединенный через атом углерода, и когда гетероциклильный ...

КАРБОКСАМИДНЫЕ СОЕДИНЕНИЯ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНГИБИТОРОВ КАЛЬПАИНОВ

Настоящее изобретение относится к новым карбоксамидным соединениям формулы I-A' или I-A", а также к их таутомерам и к их фармацевтически приемлемым солям, где Rобозначает водород, C-С-алкил, С-С-циклоалкил-С-С-алкил, арил-С-С-алкил или гетарил-С-С-алкил, где арил и гетарил в 2 последних упомянутых радикалах могут быть незамещенными или иметь один радикал R; где Rпредставляет C-С-алкокси, Rвыбирают независимо друг от друга из галогена, CN, CF, О-CF, O-CHF, C-С-алкила, C-С-алкокси, гетарила, O-СН-арила, - (CH)-NRRс р=0 или 1; где Rпредставляет собой C-С-алкил или SO-С-С-алкил, Rпредставляет собой C-С-алкил или два радикала Rи Rвместе образуют с атомом N 5- или 6-членный необязательно замещенный С-С-алкилом азотсодержащий гетероцикл, который может необязательно иметь один гетероатом из группы О и N, в качестве членов кольца, Rобозначает C-С-алкил, С-С-циклоалкил, арил, гетарил, где арил и гетарил в последних двух упомянутых радикалах могут быть незамещенными или нести 1, 2 или 3 идентичных ...

СОЕДИНЕНИЯ, МОДУЛИРУЮЩИЕ ВНУТРИКЛЕТОЧНЫЙ КАЛЬЦИЙ

Изобретение относится к соединениям формулы (I):где: A, J, R1, R4, X, Z представлены в п.1 формулы изобретения, а также к фармацевтической композиции, содержащей такие соединения, модулирующие активность депо-управляемых кальциевых (SOC) каналов. Кроме того, в данном изобретении описаны способы применения таких модуляторов SOC-каналов для лечения заболеваний или состояний, при которых может быть полезно ингибирование активности SOC-каналов. 4 н. и 13 з.п. ф-лы, 5 табл., 2 ил., 8 пр.

Соединение, ингибирующее активности киназ ВТК и/или JAK3

Настоящее изобретение относится к новому соединению формулы I, или его стереоизомеру, или фармацевтически приемлемой соли, обладающим свойствами ингибитора активности тирозинкиназы Брутона (ВТК) и/или Янус-киназы 3 (JAK3). Соединение может найти применение при лечении таких заболеваний, как ревматоидный артрит, остеоартрит, юношеский артрит, системная красная волчанка, псориаз и псориатический артрит, рак, выбранный из группы, состоящей из В-клеточного хронического лимфоцитарного лейкоза, острого лимфоцитарного лейкоза, неходжкинской лимфомы, лимфомы Ходжкина, диффузной крупноклеточной В-клеточной лимфомы, лимфомы клеток мантии и мелкоклеточной лимфоцитарной лимфомы. В формуле IR представляет собой Сциклоалкил, замещенный группой -NRW; 4-10-членную насыщенную N-гетероциклическую группу, которая содержит только один атом азота в своем кольце и этот атом азота замещен W; или Салкил, замещенный 4-10-членной насыщенной N-гетероциклической группой, которая содержит только один атом азота в своем ...

НОВОЕ ПРОИЗВОДНОЕ НИКОТИНАМИДА ИЛИ ЕГО СОЛЬ

Изобретение относится к производным никотинамида формулы (I), обладающим свойством ингибитора Syk-киназы, и к фармацевтической композиции на их основе. В общей формуле (I) R1 обозначает атом галогена; R2 обозначает заместитель, представленный следующей формулой (II-1) , в R3 обозначает пиридильную группу, представленную следующими формулами (VIII-1) или (VIII-2), R4 и R5 обозначают атом водорода. Значения других радикалов раскрыты в формуле изобретения. 5 н. и 8 з.п. ф-лы, 2 ил., 25 табл., 47 пр.

АЗАСПИРОПРОИЗВОДНЫЕ В КАЧЕСТВЕ АНТАГОНИСТОВ TRPM8

Изобретение относится к соединению формулы (I) или его фармацевтически приемлемым солям. В формуле (I) A обозначает фенил, 5-6-членный гетероарил, содержащий от 1 до 3 гетероатомов, выбранных из группы, состоящей из азота, кислорода и серы, или 9-членный бициклический гетероарил, содержащий один гетероатом, выбранный из азота и кислорода; B обозначает фенил, инданил, 5-6-членный гетероарил, содержащий от 1 до 4 гетероатомов, выбранных из группы, состоящей из азота, кислорода и серы, или 9-11-членный бициклический гетероарил, содержащий от 1 до 4 гетероатомов, выбранных из группы, состоящей из азота и кислорода; L независимо выбран из группы, состоящей из химической связи, кислорода, серы, -NR-, -(CRR)-, -O(CRR)-, -(CRR)O-, -N(R)(CRR)O- и -O(CRR)N(R)-; X независимо выбран из группы, состоящей из -CH-, кислорода и NH; значения остальных радикалов указаны в формуле изобретения. Изобретение также относится к индивидуальным соединениям, к применению соединения, к способу лечения состояния или ...

НЕКОТОРЫЕ ИНГИБИТОРЫ ПРОТЕИНКИНАЗЫ

Изобретение относится к соединению формулы (I) и/или его фармацевтически приемлемой соли. В формуле (I) X представляет собой C; Y представляет собой O или S; 6-5-членная конденсированная кольцевая система A-B выбрана из:, Q выбран из гетероарила; Rвыбран из: водорода, Cалкила, гетероциклила, гетероциклил-Cалкила, где гетероциклил является незамещенным или замещен, по меньшей мере, одним заместителем, при этом один, два, три или четыре заместителя независимо выбраны из R; Rвыбран из: Cциклоалкила, где циклоалкил является незамещенным или замещен, по меньшей мере, одним заместителем, независимо выбранным из R; Rи Rнезависимо выбраны из: водорода, Cалкила и Cциклоалкила; или Rи Rвместе с атомами азота, к которым они присоединены, образуют 4-6-членное кольцо, содержащее 0 или 1 гетероатом, независимо выбранный из кислорода и азота, и необязательно замещенное 1 группой R; каждый Rнезависимо выбран из: Cалкила, -C(O)R; каждый Rнезависимо выбран из: -Cалкила, -OR, -NRR, -(CRR)OR, -(CRR)S(O)R, ...

Ингибитор вируса гепатита В (ВГВ)

Настоящее изобретение относится к области органической химии, а именно к применению эфира 4-аминофуро[2,3-d]пиримидин-5-карбоновой кислоты формул 1.1, 1.2 или 1.3для ингибирования вируса гепатита В. Технический результат: предложено новое применение эфиров 4-аминофуро[2,3-d]пиримидин-5-карбоновой кислоты в качестве ингибиторов вируса гепатита В. 1 табл., 35 пр.

1-ЦИАНОЦИКЛОПРОПИЛЬНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ КАТЕПСИНА К

Настоящее изобретение относится к соединениям формулы (I), где значения заместителей представлены в описании, обладающим ингибирующей активностью в отношении катепсина К. Также к фармацевтическим композициям для лечения заболеваний, ассоциированных с активностью цистеиновой протеазы, и к способам ингибирования катепсина К у млекопитающего, нуждающегося в таком лечении, путем введения млекопитающему эффективного количества соединения. В изобретении также заявлено применение соединения формулы (I) или его фармацевтически приемлемой соли в изготовлении лекарственного средства для применения в ингибировании катепсина К у теплокровного животного. 4 н. и 6 з.п. ф-лы, 45 пр., 5 сx.

СОЕДИНЕНИЯ ЗАМЕЩЕННЫХ ДИАЗЕПАНОВ В КАЧЕСТВЕ АНТАГОНИСТОВ ОРЕКСИНОВЫХ РЕЦЕПТОРОВ

Описываются новые соединения замещенного диазепана, представляющие собой различные гетероциклические системы, в том числе и конденсированные, фармацевтические композиции, содержащие данные соединения, и применение указанных соединений и композиций для профилактики или лечения неврологических и психиатрических расстройств и заболеваний, в которые вовлечены орексиновые рецепторы. 10 н. и 3 з.п., 1 табл.

ПРОИЗВОДНЫЕ ФУРО[3,2-c]ПИРИДИНА ИЛИ ТИЕНО[3,2-c]ПИРИДИНА, ПОЛЕЗНЫЕ ДЛЯ ЛЕЧЕНИЯ НИКТУРИИ

Изобретение относится к области органической химии, а именно к гетероциклическому соединению формулы (I), или к его фармацевтически приемлемой соли, где X представляет собой O или S; пунктирная линия обозначает двойную химическую связь; Rпредставляет собой низший алкил, который необязательно имеет один заместитель, выбранный из группы G, Cциклоалкил, или -низший алкилен-(Cциклоалкил); Rи Rявляются одинаковыми или отличаются друг от друга и представляют собой H или низший алкил; Rпредставляет собой -низший алкилен-X-низший алкил, -низший алкилен-X-низший алкилен-Cциклоалкил, -низший алкилен-Cциклоалкил, или -низший алкилен-X-Cциклоалкил; Xпредставляет собой O или S(O), где n представляет собой 0, 1 или 2; Rпредставляет собой OH, NHили -O-низший алкил, и Rпредставляет собой H; или Rи Rсвязаны друг с другом с образованием вместе с -C(=O)-C-O-, к которому они присоединены, 2,2-ди(низший алкил)-4-оксо-1,3-диоксолан-5,5-диила; группа Gсостоит из галогена и OH. Также изобретение относится к фармацевтической ...

СПОСОБ ПОЛУЧЕНИЯ ТЕТРАГИДРОФУРО[3,2-c]ПИРИДИНОВ

Изобретение относится к области органической химии, а именно к способу получения замещенных тетрагидрофуро[3,2-с]пиридинов общей формулы I, которые могут найти применение как вещества, обладающие потенциальной биологической активностью широкого спектра действия. Способ осуществляется взаимодействием легкодоступного 2-(5-метилфуран-2-ил)этиламина и замещенных бензальдегидов при кипячении в ацетонитриле с образованием соответствующих иминов и последующей циклизацией полученных иминов в уксусной кислоте при 70°С в присутствии концентрированной соляной кислоты с последующей обработкой реакционной смеси раствором NaOH при комнатной температуре с образованием целевых тетрагидрофуро[3,2-с]пиридинов Ia-и. Технический результат изобретения заключается в создании простого и эффективного метода синтеза замещенных тетрагидрофуро[3,2-c]пиридинов формулы Iа-и, позволяющего получать целевые продукты с хорошими выходами, а также варьировать заместители в 4-м положении гетероциклического ядра. 2 табл., ...

ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ 5, 6, 6А, 11B-ТЕТРАГИДРО-7-ОКСА-5-АЗАБЕНЗО[С]ФЛУОРЕН-6-КАРБОНОВОЙ КИСЛОТЫ В КАЧЕСТВЕ NMDA-АНТАГОНИСТОВ

... 1. Замещенные производные 5,6,6а,11b-тетрагидро-7-окса-5-азабензо[с]флуорен-6-карбоновой кислоты общей формулы I в представленном виде либо в виде их кислот или их оснований, либо в виде их солей, прежде всего физиологически совместимых солей, либо в виде их сольватов, прежде всего гидратов, прежде всего в виде их физиологически совместимых солей с катионами или основаниями либо с анионами или кислотами, необязательно в виде их рацематов, их чистых стереоизомеров, прежде всего энантиомеров или диастереомеров либо в виде смесей стереоизомеров, прежде всего энантиомеров или диастереомеров, в любом их соотношении в смеси, где R1, R2, R3 и R4 независимо друг от друга обозначают Н, F, Cl, Br, I, CN, NO2 или С1-С18алкил, С2-С18 алкенил либо С2-С18алкинил, каждый из которых является разветвленным либо неразветвленным, одно- или многозамещенным либо незамещенным, С3-С8циклоалкил, который является насыщенным либо ненасыщенным, одно- или многозамещенным либо незамещенным, соответственно соответствующий ...

АНАЛОГИ ЦИКЛОПАМИНА

... 1. Соединение, представленное формулой: ! ! или его фармацевтически приемлемая соль; ! где R1 является H, алкилом, -OR, амино, сульфонамидо, сульфамидо, -OC(O)R5, -N(R5)C(O)R5 или сахаром; ! R2 является H, алкилом, алкенилом, алкинилом, арилом, циклоалкилом, нитрилом или гетероциклоалкилом; ! или R1 и R2 вместе образуют =O, =S, =N(OR), =N(R), =N(NR2) или =C(R)2; !R3 является H, алкилом, алкенилом или алкинилом; ! R4 является H, алкилом, алкенилом, алкинилом, арилом, циклоалкилом, гетероциклоалкилом, аралкилом, гетероарилом, гетероаралкилом, галоалкилом, -OR5, -C(O)R5, -CO2R5, -SO2R5, -C(O)N(R5)(R5), -[C(R)2]q-R5, -[(W)-N(R)C(O)]qR5, -[(W)-C(O)]qR5, -[(W)-C(O)O]qR5, -[(W)-OC(O)]qR5, -[(W)-SO2]qR5, -[(W)-N(R5)SO2]qR5, -[(W)-C(O)N(R5)]qR5, -[(W)-O]qR5, -[(W)-N(R)]qR5, -W-NR5 3 +X- или -[(W)-S]qR5; ! где каждый W независимо является дирадикалом; ! каждый q независимо равен для каждого случая 1, 2, 3, 4, 5 или 6; ! X- является галогенидом; ! каждый R5 независимо является H, алкилом, алкенилом ...

БИЦИКЛИЧЕСКИЕ ПИРИДИНЫ И ПИРИМИДИНЫ В КАЧЕСТВЕ ИНГИБИТОРОВ КИНАЗЫ Р38

... 1. Соединение формулы I где А означает N или СН, R1 означает водород, алкил или аралкил, R2 означает алкил, гидроксиалкил, (R'')2 NCO-алкилен- (где каждый R'' независимо означает водород или алкил), циклоалкил, гетероциклил, арил, гетероарил или гетероалкил, X означает О, NR3 или S, где R3 означает водород, алкил или арил, и Y означает химическую связь, О, N(R'), C(=O), CH(OR'), CHR' или S(O)n, где n равно 0, 1 или 2, а R' означает водород или алкил, а R означает арил или гетероарил, и его изомер, фармацевтически приемлемая соль, сложный эфир или пролекарство. 2. Соединение по п.1, в котором все заместители имеют значения, указанные в п.1, за исключением того, что R2 не означает гетероалкил. 3. Соединение по п.1, где А означает N или СН, R1 означает водород, алкил или аралкил, R2 означает алкил, гидроксиалкил, циклоалкил, гетероциклил, арил, гетероарил, Х означает О, NR3 или S, где R3 означает водород или метил, Y означает О, NR', C(=O), CH(OR'), CHR' или S(O)n, где n равно 0, 1 или 2, ...

БЕНЗИЗОКСАЗОЛЫ И АЗАБЕНЗИЗОКСАЗОЛЫ КАК АЛЛОСТЕРИЧЕСКИЕ ПОТЕНЦИАТОРЫ MGLUR4, КОМПОЗИЦИИ И СПОСОБЫ ЛЕЧЕНИЯ НЕВРОЛОГИЧЕСКИХ ДИСФУНКЦИЙ

... 1. Соединение, имеющее структуру, представленную формулойгде каждый Х независимо выбран из группы, которую составляют CRи N;Y выбран из группы, которую составляют О и S;Z выбран из группы, которую составляют CRи N;W выбран из группы, которую составляют О и NH;А выбран из С-С-циклоалкила, или С-С-циклоалкенила, или арила, или гетероарила, или С-С-гетероциклоалкила, или С-С-гетероциклоалкенила, или 3-8-членного цикла, содержащего С, О, S и/или N; R выбран из группы, которую составляют водород, галоген, С-алкил, С-никлоалкил, ОС-алкил (который может содержать С-членный цикл, содержащий С, О, S или N, факультативно замещенный одним или несколькими R), NRR, CONRR, S(O)NRR, CN или CF;Rнезависимо выбран из группы, которую составляют водород, галоген, С-алкил, С-циклоалкил, ОС-алкил (который может содержать С-членный цикл, содержащий С, О, S или N, факультативно замещенный одним или несколькими R), NRR, CORR, CRR, CONRR, S(O)NRR, CN, CFили S(O)С-алкил (который может содержать С-членпый цикл, содержащий ...

КОНДЕНСИРОВАННЫЕ ГЕТЕРОЦИКЛИЧЕСКИЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ МОДУЛЯТОРОВ S1P

... 1. Конденсированное гетероциклическое производное формулы ():,гдеR1 выбран изциано,(2-4C)алкенила, (2-4C)алкинила, (1-4C)алкила, каждый из которых необязательно замещен CN или одним или несколькими атомами фтора,(3-6C)циклоалкила, (4-6C)циклоалкенила или (8-10C)бициклической группы, каждый из которых необязательно замещен галогеном или (1-4C)алкилом, необязательно замещенным одним или несколькими атомами фтора,фенила, бифенила, нафтила, каждый из которых необязательно замещен одним или несколькими заместителями, независимо выбранными из галогена, циано, (1-4C)алкила, необязательно замещенного одним или несколькими атомами фтора, (1-4C)алкокси, необязательно замещенного одним или несколькими атомами фтора, амино, диметиламино, и (3-6C)циклоалкила, необязательно замещенного фенилом, который может быть замещен (1-4C)алкилом или галогеном, ифенила, замещенного фенокси, бензила, бензилокси, фенилэтила или моноциклического гетероцикла, каждый из которых необязательно замещен (1-4C)алкилом,Z представляет ...

АМИДНОЕ СОЕДИНЕНИЕ

Изобретение относится к амидным соединениям, перечень которых представлен в пункте 1 формулы. Соединения проявляют антагонистическую активность в отношении ЕР4 рецептора, что позволяет использовать их в качестве активного ингредиента фармацевтической композиции для лечения хронической почечной недостаточности или диабетической нефропатии. 5 н. и 22 з.п. ф-лы, 1 список последовательностей, 228 табл., 86 пр.

Способ получения этил 3-(3-гидрокси-1,4-диоксо-1,4-дигидронафталин-2-ил)-2,5,10-триоксо-10b-фенил-1,2,3,5,10,10b-гексагидро-3аН-нафто[2',3':4,5]фуро[3,2-b]пиррол-3а-карбоксилатов

Изобретение относится к способу получения новых соединений- этил 3-(3-гидрокси-1,4-диоксо-1,4-дигидронафталин-2-ил)-2,5,10-триоксо-10b-фенил-1,2,3,5,10,10b-гексагидро-3aH-нафто[2',3':4,5]фуро[3,2-b]пиррол-3а-карбоксилатов общей формулы I, где R=CHPh(a), СН-с(b), Ph(c), CHOMe-4 (d), СНМе-4 (е), CHCl-4 (f), Me(g), путем взаимодействия 5-фенил-4-этоксикарбонил-1H-пиррол-2,3-дионов с 2-гидроксинафталин-1,4-дионом в соотношении 1:2 в присутствии уксусной кислоты в среде инертного апротонного растворителя. Технический результат - получение новых соединений, которые могут быть использованы в качестве исходных продуктов для синтеза новых гетероциклических систем и в фармакологии как обладающие противомикробной активностью. 2 з.п. ф-лы, 1 табл., 2 пр.(I) ...

Способ получения производных фуро[3,4-с]пиридин-1(3Н)-онов

Изобретение относится к способу получения производных фуро[3,4-с]пиридин-3(1H)-онов общей формулы (1), где X=Cl, R1=R2=СН3; X=Cl, R1=R2=С6Н5; X=Cl, R1+R2=(СН2)4; X=Br, R1=R2=СН3, который включает взаимодействие соответствующих 5,6-дизамещенных 2-галогенпиридин-3,4-дикарбоновых кислот с пропионовым ангидридом при нагревании в течение 10-12 часов и восстановление промежуточно получаемого 4-галогенфуро[3,4-с]пиридин-1,3-диона борогидридом натрия в течение 3-4 часов при комнатной температуре с последующим упариванием реакционной массы на роторном испарителе под вакуумом, разбавлением остатка водой, нейтрализацией 10%-ным водным раствором HCl, экстракцией этилацетатом, очисткой этилацетатных вытяжек колоночной хроматографией и перекристаллизацией продукта после хроматографии из пропан-2-ола. Технический результат – разработан способ получения новых производных соединений формулы (I), которые могут найти свое применение в медицине для лечения или профилактики аутоиммунных и воспалительных заболеваний ...

ИЗОХИНОЛИН-3-ИЛОВЫЕ КАРБОКСАМИДЫ И ИХ ПОЛУЧЕНИЕ И ПРИМЕНЕНИЕ

НОВЫЕ АНАЛОГИ СС-1065 И ИХ КОНЪЮГАТЫ

... 1. Соединение формулы () или ():или его фармацевтически приемлемая соль, гидрат или сольват, гдепредставляет собой ДНК-связывающую группу и выбран из группы, состоящей изRпредставляет собой удаляемую группу;R, R, R, R, R, R, Rи Rнезависимо выбраны из H, OH, SH, NH, N, NO, NO, CF, CN, C(O)NH, C(O)H, C(O)OH, галогена, R, SR, S(O)R, S(O)R, S(O)OR, S(O)OR, OS(O)R, OS(O)R, OS(O)OR, OS(O)OR, OR, NHR, N(R)R,N(R)(R)R, P(O)(OR)(OR), OP(O)(OR)(OR), SiRRR, C(O)R, C(O)OR, C(O)N(R)R, OC(O)R, OC(O)OR, OC(O)N(R)R, N(R)C(O)R, N(R)C(O)ORи N(R)C(O)N(R)R, гдеR, Rи Rнезависимо выбраны из H и необязательно замещенного Cалкила или Cгетероалкила,или R+R, и/или R+Rнезависимо выбраны из =O, =S, =NOR, =C(R)Rи =NR, где Rи Rнезависимо выбраны из H и необязательно замещенного Cалкила, два или более R, R, R, R, R, Rи Rнеобязательно соединены одной или несколькими связями с образованием одного или нескольких необязательно замещенных карбоциклов и/или гетероциклов;выбран из O, C(R)(R) и NR, где Rи Rимеют те же значения ...

СОЕДИНЕНИЯ ЗАМЕЩЕННЫХ ДИАЗЕПАНОВ В КАЧЕСТВЕ АНТАГОНИСТОВ ОРЕКСИНОВЫХ РЕЦЕПТОРОВ

... 1. Соединение формулы I: ! ! где: ! R1 является фенилом, замещенным R1a, R1b и R1c; ! R2 является гетероарилом, замещенным R2a, R2b и R2c; ! R1a, R1b, R1c, R2a, R2b и R2c независимо выбирают из группы, состоящей из ! (1) водорода, ! (2) галогена, ! (3) гидроксила, ! (4) -(С=О)m-On-C1-6алкила, где m равно 0 или 1, n равно 0 или 1 (где, если m равно 0 или n равно 0, то присутствует связь), где соседние R2a и R2b или R2b и R2c могут быть соединены вместе, с образованием циклоалкильного или циклоалкокси кольца, и где алкил является незамещенным или замещен одним или несколькими заместителями, выбранными из R13, ! (5) -(С=О)m-On-C3-6циклоалкила, где циклоалкил является незамещенным или замещен одним или несколькими заместителями, выбранными из R13, !(6) -(С=О)m-C2-4алкенила, где алкенил является незамещенным или замещен одним или несколькими заместителями, выбранными из R13, ! (7) -(С=О)m-C2-4алкинила, где алкинил является незамещенным или замещен одним или несколькими заместителями, выбранными ...

ГАЛОГЕНИРОВАННЫЕ ХИНАЗОЛИН-THF-АМИНЫ В КАЧЕСТВЕ ИНГИБИТОРОВ PDE1

АМИДЫ КОНДЕНСИРОВАННОГО ПИПЕРИДИНА В КАЧЕСТВЕ МОДУЛЯТОРОВ ИОННЫХ КАНАЛОВ

АНТИБАКТЕРИАЛЬНЫЕ СОЕДИНЕНИЯ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

... 1. Соединение формулы (I), формулы (II) или формулы (III):или его форма, гдеX представляет собой связь, N(R), S, O, -CH(R)-, -CH(R)-CH(R)-, -CH(R)-CH(R)-CH(R)-, -C(R)=C(R)-, -C(R)=C(R)-CH(R)-, -CH(R)-C(R)=C(R)-, -O-CH(R)-, -CH(R)-O-, -N(R)-CH(R)-, -CH(R)-N(R)-, -S-CH(R)-, -CH(R)-S-, -O-CH(R)-CH(R)-, -CH(R)-O-CH(R)-, -CH(R)-CH(R)-O-, -N(R)-CH(R)-CH(R)-, -CH(R)-N(R)-CH(R)-, -CH(R)-CH(R)-N(R)-, -S-CH(R)-CH(R)-, -CH(R)-S-CH(R)-, -CH(R)-CH(R)-S-; -O-C(O)-CH(R)-, -C(O)-O-CH(R)-, -CH(R)-O-C(O)-, -CH(R)-C(O)-O-, -N(R)-C(O)-CH(R)-, -C(O)-N(R)-CH(R)-, -CH(R)-N(R)-C(O)-, -CH(R)-C(O)-N(R)-, -S-C(O)-CH(R)-, -C(O)-S-CH(R)-, -CH(R)-S-C(O)- или -CH(R)-C(O)-S-;Yпредставляет собой -N(R)- или -O-;Yпредставляет собой -C(R)-, -N(R)- или -O-; где пунктирная линия представляет собой двойную связь, которая присутствует, если Yпредставляет собой -C(R)- и отсутствует, если Yпредставляет собой -N(R)- или -O-;Z представляет собой N(R), S, O, C(O) или -CH(R)-;Rпредставляет собой водород, галоген, гидроксил, оксо, циано ...

ИНГИБИТОРЫ NAMPT И ROCK

... 1. Соединение (Ic) и его фармацевтически приемлемые солиформула (Ic);гдеX, Xи Xпредставляют собой CH; илиXи Xпредставляют собой CH; и Xпредставляет собой N; илиXи Xпредставляют собой CH; и Xпредставляет собой CR; илиXи Xпредставляют собой CH; и Xпредставляет собой CR; илиXпредставляет собой CH; и Xи Xпредставляют собой CR; илиXпредставляет собой CH; и Xи Xпредставляют собой N; илиXи Xпредставляют собой CH; и Xпредставляет собой N; илиXпредставляет собой CH; Xпредставляет собой N; и Xпредставляет собой CR; илиXпредставляет собой CR; Xпредставляет собой N; и Xпредставляет собой CH; илиXпредставляет собой N; Xпредставляет собой CR; и Xпредставляет собой CH; илиXпредставляет собой N; Xпредставляет собой CR; и Xпредставляет собой N;Rпредставляет собой R, OR, SR, S(О)R, SOR, C(О)R, C(О)OR, OC(О)R, NHR, N(R), C(О)NH, C(О)NHR, C(О)N(R), NHC(О)R, NRC(О)R, NHC(О)OR, NRC(О)OR, SONH, SONHR, SON(R), NHSOR, NRSOR, NHSONHR, NHSON(R), NRSONHR, NRSON(R), C(О)NHSOR, NHSONHR, F, Cl, Br, I, CN, NH, NO, N, ...

КАРБОКСАМИДНЫЕ СОЕДИНЕНИЯ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНГИБИТОРОВ КАЛЬПАИНОВ

... 1. Карбоксамидное соединение формулы IгдеRобозначает водород, C-C-алкил, C-C-алкенил, C-C-алкинил, где 3 последних упомянутых радикала могут быть частично или полностью галогенированными и/или иметь 1, 2 или 3 заместителя R,C-C-циклоалкил, C-C-циклоалкил-C-C-алкил, где CHгруппа в циклоалкильном фрагменте двух последних упомянутых радикалов может быть замещена O, NH, или S, или два соседних атома C могут образовывать двойную связь, где циклоалкильный фрагмент может дополнительно иметь 1, 2, 3 или 4 радикала R,арил, гетарил, арил-C-C-алкил, арил-C-C-алкенил, гетарил-C-C-алкил или гетарил-C-C-алкенил, где арил и гетарил в 6 последних упомянутых радикалах могут быть незамещенными или иметь 1, 2, 3 или 4 идентичных или разных радикалов R; гдеRвыбирают независимо друг от друга из OH, SH, COOH, CN, OCHCOOH, C-C-алкокси, C-C-галогеналкокси, C-C-циклоалкилокси, C-C-алкилтио, C-C-галогеналкилтио, COOR, CONRR, SONRR, -NR-SO-R, NR-CO-R, SO-R, NRR,Rвыбирают независимо друг от друга из OH, SH, COOH, ...

Ингибитор вируса гепатита В (ВГВ)

ПРОИЗВОДНЫЕ БЕНЗОДИАЗЕПИНА КАК ИНГИБИТОРЫ RSV

АЗЕТИДИНИЛДИАМИДЫ В КАЧЕСТВЕ ИНГИБИТОРОВ МОНОАЦИГЛИЦЕРИН-ЛИПАЗЫ

... 1. Соединение формулы (I)Формула (I)где Y и Z независимо выбраны из группы a) или b) таким образом, что один из Y или Z выбран из группы a), а другой - из группы b);Группа a) представляет собойi) замещенный Cарил;ii) трифторметил;iii) Cциклоалкил илиiv) гетероарил, выбранный из группы, состоящей из тиенила, фуранила, тиазолила, изотиазолила, оксазолила, пирролила, пиридинила, изоксазолила, имидазолила, фуразан-3-ила, бензотиенила, тиено[3,2-b]тиофен-2-ила, пиразолила, триазолила, тетразолила и [1,2,3]тиадиазолила;где Cарил замещен, а гетероарил необязательно замещен одним заместителем, выбранным из группы, состоящей из фтора, хлора, брома, Cалкила, циана, Cалкилкарбониламина и трифторметила;Группа b) представляет собойi) аннелированный с бензольным кольцом Cциклоалкил(C)алкил, где Cциклоалкил необязательно замещен 1-4 метиловыми заместителями;ii) Cарил(C)алкил;iii) Cарил(C)алкенил;iv) фенил(C)алкинил;v) Cциклоалкил, необязательно замещенный одним или двумя заместителями, независимо выбранными ...

ФАРМАЦЕВТИЧЕСКИЕ СОЕДИНЕНИЯ

... 1. Соединение, которое представляет собой конденсированный пиримидин формулы (Ia) или (Ib) ! ! где Х представляет собой О или S; ! R1 представляет собой группу формулы ! ! R2 представляет собой Н, галогено или C1-C6алкил; ! R4 и R5 образуют вместе с атомом N, к которому они присоединены, группу, выбранную из пиперазина, пиперидина, пирролидина, оксазолидинона, диазепана и 2,5-диазабицикло[2,2,1]-гептана, где эта группа является незамещенной или замещена группой -[(alk)q-NR]r-S(O)2-(alk)q-Z либо -C(O)-(alk)q-S(O)2Z, где Z представляет собой R10 либо -NR11R12, либо незамещенным C1-C6алкилом, гидрокси-С1-С6алкилом, оксо (=O), -(alk)q-OR, -C(O)-C(R')2-N(R)2, -C(R)2-C(O)-N(R)2, -C(O)-(NR)q-(alk)q-OR, -С(O)-циклил, -C(O)R, -C(O)OR, -C(O)-Tet или -NR13R14; ! либо один из R4 и R5 представляет собой C1-C6алкил, -(alk)q-гетероциклил или -(alk)q-OR, а другой представляет собой группу пиперазин, пиперидин, пирролидин, сульфонилпиран или -(alk)q-гетероциклил, где указанная группа пиперазин, пиперидин ...

ЗАМЕЩЕННЫЕ ТЕТРАГИДРОХИНОЛИНЫ

... 1. Соединения формулы I ! ! в которой ! W представляет собой СИ или N, ! R1, R2, R3, независимо друг от друга, представляют собой Н, А, арил, гетероарил, Hal, -(CY2)n-SA, -(CY2)n-SCF3, -(CY2)n-SCN, -(CY2)n-CF3, -(CY2)n-OCF3, R, NR-NR2, X(CY2)nXR, X(CY2)nY, (СY2)n-циклоалкил, ! (CY2)nCH=CH2, циклоалкил, -SСН3, -SCN, -СF3, -ОСF3, -ОА, -(CY2)n-OH, -(CY2)n-CO2R, -(CY2)n-CN, -(CY2)n-Hal, -(CY2)n-Y, -(CY2)nRa, ! -(CY2)n-NR2, (CY2)n-OA, (CY2)n-OCOA, -SCF3, (CY2)n-CONR2, -(CY2)n-NHCOA, -(CY2)n-NHSO2A, SF3, 5;(СН3)3, СО-(СY2)n-СН3, -(СY2)n-пирролидон. (CH2)nNRCOOR, NRCOOR, NCO, ! (CH2)nCOOR, NCOOR, (CH2)nOH, NR(CH2)nNR2, C(OH)R2, ! NR(CH2)nOR, NCOR, (СН2)n-арил, (СН2)n-гетероарил, (CH2)nR1, ! (СН2)nХ(СН2)n-арил, (СН2)nХ(СН2)n-гетероарил, (CH2)nCONR2, ! XCONR(CH2)nNR2, N[(CH2)nXCOOR]CO(CH2)n-арил, ! N[(CH2)nXR]CO(CH2)n-apил, ! N[(CH2)nXR]CO(CH2)nX-apил, ! N[(CH2)nXR]SO2(CH2)n-арил, N[(CH2)nNRCOOR]CO(CH2)n-aрил, ! N[(CH2)nNR2]CO(CH2)n-арил, ! N[(CH2)nNR2]CO(CH2)nNR-арил, ! N[(CH2)nNR2]SO2(CH2)n-арил ...

ПРОИЗВОДНЫЕ ПИПЕРИДИНДИОНА

АЗАГЕТЕРОЦИКЛЫ, КОМБИНАТОРНАЯ БИБЛИОТЕКА, ФОКУСИРОВАННАЯ БИБЛИОТЕКА, ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

... 1. Азагетероциклы общей формулы 1 где R1a представляет собой заместитель аминогруппы; Rb и Rc вместе с атомом углерода, с которым они связаны, образуют карбонильную группу, атом углерода которой находится в цикле; R1d и R2d вместе с атомом углерода, с которым они связаны, образуют карбонильную группу, атом углерода которой находится в цикле; Х представляет собой группу NR2a, атом азота которой находится в цикле, a R2aпредставляет собой заместитель аминогруппы; W, Y и Z вместе образуют метиленовую группу CR3dR4d, в которой R3d и R4d, независимо друг от друга, представляют собой заместитель циклической системы или R3d и R4d вместе с атомом углерода, с которым они связаны, образуют через R3d и R4d циклоалкил или гетероциклил; или R2a, вместе с атомом азота с которым он связан, и R3d, вместе с атомом углерода, с которым он связан, замыкают через R2aи R3d азагетероцикл; или где R1a представляет собой заместитель аминогруппы; Rb представляют собой карбамоильную группу; Rc представляют собой заместитель ...

СОЕДИНЕНИЯ, КОМПОЗИЦИИ И СПОСОБЫ, ПОДХОДЯЩИЕ ДЛЯ МОБИЛИЗАЦИИ ХОЛЕСТЕРИНА

... 1. Соединение Формулы (II):или его фармацевтически приемлемая соль, гдекаждый Rнезависимо представляет собой -Н, -гидрокарбил, арил, -аралкил, -гетероарил, -гетероциклил, -С(О)О(алкил), -ОС(O)(алкил), -C(O)NH, -С(О)NH(алкил), -С(О)N(алкил)(алкил), -NHC(O)(алкил), N(алкил)С(O)(алкил) или -SONH;каждый Rнезависимо представляет собой -Н, -ОН, -NH, -NH(алкил), -N(алкил)(алкил), гидрокарбил, -O-алкил, -O-алкенил, арил, -O-арил, аралкил, -O-аралкил, гетероарил, -O-гетероарил, гетероциклил, -O-гетероциклил, галоген, -OCF, -С(О)О(алкил), -ОС(О)(алкил), -C(O)NH, -С(О)NH(алкил), -С(О)N(алкил)(алкил), NHC(O)(С-С-алкил), N(алкил)С(О)(алкил), -ОС(О)О(алкил), -OC(O)NH, -ОС(О)NH(алкил), -ОС(О)N(алкил)(алкил), -CHNH, -CHN(алкил) или -SONH;каждый из Q, Qи Qнезависимо представляет собой CRили N;Х представляет собой CHR, S, О или NR; икаждый m независимо представляет собой целое число от 0 до 3.2. Соединение или фармацевтически приемлемая соль по п.1, отличающиеся тем, что Rпредставляет собой Н, а Rпредставляет ...

БИЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ АЛЛОСТЕРИЧЕСКИХ ИНГИБИТОРОВ SHP2

ИНГИБИТОРЫ ДНК-ПК

СОЕДИНЕНИЯ ПИРРОЛИДИНИЛМОЧЕВИНЫ И ПИРРОЛИДИНИЛТИОМОЧЕВИНЫ КАК ИНГИБИТОРЫ КИНАЗЫ TRKA

... 1. Соединение Формулы I:или его стереоизомеры, таутомеры или фармацевтически приемлемые соли, сольваты или пролекарства, где:фрагмент Y-B и фрагмент NH-C(=X)-NH находятся в транс-конфигурации;R, R, Rи Rнезависимо выбраны из Н и (1-3С)алкила;X представляет собой О, S или NH;Rпредставляет собой (1-3С алкокси)(1-6С)алкил, (трифторметокси)(1-6С)алкил, (1-3С сульфанил)(1-6С)алкил, монофтор(1-6С)алкил, дифтор(1-6С)алкил, трифтор(1-6С)алкил, тетрафтор(2-6С)алкил, пентафтор(2-6С)алкил, циано(1-6С)алкил, аминокарбонил(1-6С)алкил, гидрокси(1-6С)алкил, дигидрокси(2-6С)алкил, (1-6С)алкил, (1-3С алкиламино)(1-3С)алкил, (1-4С алкоксикарбонил)(1-6С)алкил, амино(1-6С)алкил, гидрокси(1-3С алкокси)(1-6С)алкил, ди(1-3С алкокси)(1-6С)алкил, (1-3С алкокси)трифтор(1-6С)алкил, гидрокситрифтор(1-6С)алкил, (1-4С алкоксикарбонил)(1-3С алкокси)(1-6С)алкил, гидроксикарбонил(1-3С алкокси)(1-6С)алкил, гетAr(СН)или Ar(СН);Rпредставляет собой Н, F или ОН;Y представляет собой связь, -O- или -ОСН-;В представляет собой Ar ...

ИНГИБИТОРЫ ФОСФОДИЭСТЕРАЗЫ ТИПА 10А

... 1. Соединение формулы I,где Q представляет собой O или S;Хпредставляет собой N или CH;Xпредставляет собой N или C-R;Xпредставляет собой О, S, -X=C(R)-, где С(R) соединен с атомом углерода, который несет R, или-Х=С(R)-, где Хсвязан с атомом углерода, который несет R;Хпредставляет собой N или C-R;Xпредставляет собой N;Het выбирают изi. моноциклического C-связанного 6-членного гетарила, имеющего 1 или 2 атом(а) азота качестве кольцевых членов, который является незамещенным или может нести 1, 2, 3 или 4 идентичных или различных заместителя R,ii. конденсированного бициклического гетарила, имеющего 1 или 2 атом(а) азота и необязательно дополнительный гетероатом, выбранный из O, S и N в качестве кольцевых членов, бензотиенила или бензофурила, где бициклический гетарил, бензотиенил и бензофурил являются, независимо друг от друга, незамещенными илимогут нести 1, 2, 3 или 4 идентичных или различных заместителя R, иiii. фенила, который несет моноциклическую гетарильную группу, имеющую 1 или 2 атом ...

ПИРИМИДИНОВОЕ ПРОИЗВОДНОЕ, СКОНДЕНСИРОВАННОЕ С НЕАРОМАТИЧЕСКИМ КОЛЬЦОМ

... 1. Конденсированное пиримидиновое производное, представленное формулой (I), или его фармацевтически приемлемая соль [Формула 10] где A представляет собой кольцо, выбранное из группы, включающей группу X1, группу X2, группу X3 и группу X4, причем атом (атомы) углерода, составляющие указанное кольцо, являются необязательно замещенными одной или несколькими группами, выбранными из группы, включающей низший алкил, -O-(низший алкил), атом галогена, карбоксил, -CO2-(низший алкил) и карбамоил, и атом серы, составляющий указанное кольцо, является необязательно окисленным, группу X1 выбирают из [Формула 11] , группу X2 выбирают из [Формула 12] , группу X3 выбирают из [Формула 13] , группу X4 выбирают из [Формула 14] ; R1 представляет собой группу, выбранную из групп (1)-(3), (1) фенил, замещенный, по меньшей мере, одним атомом галогена, который может иметь дополнительный заместитель (заместители), (2) циклопропил, циклобутил, циклопентил, циклогексил или циклогептил, каждый из которых является необязательно ...

СОЕДИНЕНИЯ И КОМПОЗИЦИИ В КАЧЕСТВЕ МОДУЛЯТОРОВ АКТИВНОСТИ GPR119

... 1. Соединение формулы I ! ! в котором ! Q представляет собой двухвалентный или трехвалентный радикал, выбранный из С6-10арила, С1-10гетероарила, С3-8циклоалкила и С3-8гетероциклоалкила; где указанный арил, гетероарил, циклоалкил или гетероциклоалкил в Q необязательно замещен вплоть до 3 раз радикалами, независимо выбранными из галогена, С1-6алкила, галогензамещенного-С1-6алкила, С1-6алкоксигруппы, галогензамещенной-С1-6алкоксигруппы, -C(O)R20 и -C(O)OR20; где R20 выбран из водорода и С1-6алкила; и необязательно связывая атом углерода, соседний с W2, через CR31, О, S или NR31 с атомом углерода Q с образованием 5-членного кольца, конденсированного с кольцами А и Q; где R31 выбран из водорода и С1-6алкила; ! W1 и W2 независимо выбраны из CR21 и N; где R21 выбран из водорода, цианогруппы, C1-6алкила и -C(O)OR25; где R25 выбран из водорода и С1-6алкила; кольцо А может содержать вплоть до 2 кольцевых атомов углерода, замещенных группой, выбранной из -С(О)-, -C(S)- и -С(=NОR30)-, и может быть ...

1-ЦИАНОЦИКЛОПРОПИЛЬНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ КАТЕПСИНА К

... 1. Соединение формулы (I) !! где ! А представляет собой циклогексановое кольцо; !R представляет собой водород; ! R1 и R2 вместе с атомом азота, к которому они присоединены, образуют 5-7-членное моноциклическое насыщенное или частично ненасыщенное гетероциклическое кольцо, которое имеет по меньшей мере один общий атом со вторым моноциклическим насыщенным, частично ненасыщенным или ненасыщенным кольцом так, что образуется бициклическая кольцевая система; ! где бициклическая кольцевая система имеет по меньшей мере один общий атом с третьим насыщенным, частично ненасыщенным или ненасыщенным кольцом так, что образуется трициклическая кольцевая система, содержащая вплоть до 19 кольцевых атомов, ! и где трициклическая кольцевая система возможно содержит вплоть до пяти гетероатомов, каждый из которых независимо выбран из атомов О, S или N и возможно замещен заместителями в количестве вплоть до трех, каждый из которых независимо выбран из фенила, бензила, нафтила, C1-6алкила, С2-6алкенила, С2-6алкинила ...

BENZYLAMINOARYL-DIHYDROPYRIDINELACTONE, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG IN ARZNEIMITTELN.

POLYMORPHE FORMEN VON N-(2,3-DIMETHYL-5,6,7,8-TETRAHYDROFURO(2,3-B)QUINOLIN-4-YL)-2-(2-OXOPYRROLIDIN-1 -YL)ACETAMID

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.

IMIDAZO-ECKIGE KLAMMER AUF 1,2 C ECKIGE KLAMMER ZU -PYRIMIDINDERIVATE, VERFAHREN ZU DEREN HERSTELLUNG UND DEREN VERWENDUNG

Heterocyclische Verbindungen und organische lichtemittierende Vorrichtungen, die diese aufweisen

Es werden heterocyclische Verbindungen, Syntheseverfahren zu ihrer Herstellung und organische lichtemittierende Anzeigevorrichtungen, die sie aufweisen, beschrieben. Die gegenständlichen heterocyclischen Verbindungen können einen aromatischen Ring oder einen heteroaromatischen Ring aufweisen, der mit einem Carbazol-, Dibenzothiophen- oder Dibenzofuranderivat kondensiert ist, wobei die Verbindungen steife Hauptkettengerüste mit hohen Glasübergangstemperaturen und hohen Schmelzpunkten aufweisen. Die gegenständlichen heterocyclischen Verbindungen können hohe elektrische Stabilität, verbesserte Ladungstransportfähigkeiten, einen hohen Wärmewiderstand und verbesserte Lichtemissionseigenschaften aufweisen, wenn sie in organischen lichtemittierenden Vorrichtungen verwendet werden. Organische lichtemittierende Anzeigevorrichtungen, die gemäß der vorliegenden Erfindung hergestellt werden, weisen eine niedrigere Ansteuerspannung, eine höhere Lichtausbeute und eine längere Lebensdauer auf.

Verfahren zur Herstellung von Phenylpiperidinocumaranen

Polynuclear heterocyclic compounds

The invention comprises compounds of the general formula or (wherein X represents oxygen or sulphur, and R1 and R2 represent alkyl or aryl groups or members of a further aromatic or cycloaliphatic ring), and the preparation thereof by the following processes: (a) reacting 5- or 6-hydrazine derivatives of the dihydrofurano- or dihydrothiophene-quinaldine series with carbonyl compounds; (b) treating 4-hydroxy-5:6-pyrrole- or indolequinaldines according to process (a) of Specification 703,277; (c) treating primary 5- or 6-aminoindoles or 2- or 3-aminocarbazoles according to process (b) of Specification 703,277. The products possess amoebicidal activity and form water-soluble salts with mineral acids, e.g. halogen hydracids, sulphuric, phosphoric and nitric acids. In examples: (1) the 6-hydrazine compound obtained from the amino compound of example (2) of Specification 703,277 by diazotization and reduction of the diazo compound with stannous chloride ...

FUSED BICYCLIC IMIDES WITH PSYCHOTROPIC ACTIVITY

Biologically active compounds

Indoleamine 2,3-Dioxygenase inhibitors and use of same in medicine

2-amino-4-arylthiazole compounds as TRPA1 antagonists

PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE

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

Novel heterocyclic compounds useful for the treatment of inflamatory and allergic disorders

PROCESSES OF MAKING AND CRYSTALLINE FORMS OF A MDM2 INHIBITOR

HEXAHYDROFUROPYRROLES AS PDE1 INHIBITORS

Antiviral drugs for treatment or prevention of dengue infection

PROCESSES OF MAKING AND CRYSTALLINE FORMS OF A MDM2 INHIBITOR

Substituted phthalazin-1(2H)-one derivatives as selective inhibitors of poly (adp-ribose) polymerase-1

HALOGENATED QUINAZOLIN-THF-AMINES AS PDE1 INHIBITORS

1,2,3,4-tetrahydro-benzofuro {3,2-c} pyridine derivatives.

The present invention concerns the compounds of formula (i), the n-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein each r1 is independently hydrogen, halogen, c1-6alkyl, nitro, hydroxy or c1-4alkyloxy; alk is c1-6alkanediyl; n is 1 or 2; d is an optionally substituted mono-, bi- or tricyclic nitrogen containing heterocycle having central b2-adrenoceptor antagonist activity. It further relates to their preparation, compositions comprising them and their use as a medicine.

NOVEL HETEROCYCLIC COMPOUNDS

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

HEXAHYDROFUROPYRROLES AS PDE1 INHIBITORS

Novel heterocyclic compounds useful for the treatment of inflamatory and allergic disorders.

2-Amino-4-arylthiazole compounds as TROA1 antagonists

AMIDE COMPOUNDS FOR THE TREATMENT OF HIV

Nitrogen-containing heterocyclic compound and agricultural fungicide

1,2, ,4-tetrahydro-benzofuro (3,2-c)pyridine derivatives

Antiviral drugs for treatment or prevention of dengue infection

Novel heterocyclic compounds useful for the treatment of inflamatory and allergic disorders

PROCESSES OF MAKING AND CRYSTALLINE FORMS OF A MDM2 INHIBITOR

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

2-Phenyl-5-heterocyclyl-tetrahydro-2H-pyran-3-amine compounds for use in the treatment of diabetes and its associated disorders

PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE

Substituted phthalazin-1(2H)-one derivatives as selective inhibitors of poly (adp-ribose) polymerase-1

Biaryl amide compounds as kinase inhibitors

Nitrogen-containing heterocyclic compound and agricultural fungicide.

HALOGENATED QUINAZOLIN-THF-AMINES AS PDE1 INHIBITORS

Novel purine derivatives and their use in the treatment of disease

Fused dihydrofurans as GPR119 modulators for the treatment of diabetes, obesity and related disorders

PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE

2-amino-4-arylthiazole compounds as TRPA1 antagonists

Transfer Hydrogenation of Cyclopamine Analogs

Provided herein is a process for the transfer-hydrogenation of ketone analogs of members of the jervine type of Veratrum alkaloids, such as cyclopamine. Also provided herein are novel ruthenium transfer-hydrogenation catalysts.

Sulfonamide, sulfamate, and sulfamothioate derivatives

The disclosure provides biologically active compounds of formula (I): and pharmaceutically acceptable salts thereof, compositions containing these compounds, and methods of using these compounds in a variety applications, such as treatment of diseases or disorders associated with E1 type activating enzymes, and with Nedd8 activating enzyme (NAE) in particular.

Novel fused pyridine compounds as casein kinase inhibitors

Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, A, R 4 , n, and R 7 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

Polymerizable composition, color filter, and method of producing the same, solid-state imaging device, and planographic printing plate precursor, and novel compound

Disclosed is a photopolymerizable composition which contains a photopolymerization initiator (A) that has a partial structure represented by the following Formula (1) and a polymerizable compound (B). In General formula (1), R 3 and R 4 each independently represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group or an alkoxy group; R 3 and R 4 may form a ring with each other; and X represents OR 5 , SR 6 , or NR 17 R 18 . The photopolymerizable composition is capable of forming a cured film that has high sensitivity, excellent intra-membrane curability and excellent adhesion to a support. The cured film is able to maintain a patterned shape even during post-heating after development and has good pattern formability, while coloring due to heating with passage of time being suppressed.

Diuretics

A compound having the structure (I) wherein R is selected from the group consisting of 1) and 2), or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating hypertension.

Heteroaryl Derivatives as CFTR Modulators

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

VLA-4 inhibitory drug

This invention relates to a VLA-4 inhibitory drug, having good oral absorbability and exhibiting sufficient anti-inflammatory effects when administered orally, wherein an active ingredient is represented by formula (I), or a salt thereof: Q represents an optionally-substituted monocyclic or bicyclic nitrogen-containing heterocyclic group having a nitrogen atom as the bonding site; Y represents an oxygen atom or CH 2 ; W represents an optionally-substituted bicyclic aromatic hydrocarbon ring group or an optionally-substituted bicyclic aromatic heterocyclic group; A 1 represents a nitrogen atom or C—R 3d wherein R 3d represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group; R 1 represents H or a C1-8 alkyl group; R 2 represents H, a halogen, a C1-8 alkoxy

LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS

Compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or diagnose diseases, disorders, or conditions associated with one or more of the lysophosphatidic acid receptors are provided. 5. The compound or pharmaceutically acceptable salt of claim 2 , wherein m=1 claim 2 , and wherein Ris hydrogen and Ris selected from the group consisting of optionally substituted phenyl claim 2 , imidazole claim 2 , pyridine claim 2 , thiazole claim 2 , and oxazole.6. The compound or pharmaceutically acceptable salt thereof of claim 2 , wherein m=1 claim 2 , and wherein Rand Rare joined together with the atom to which they are attached to form an optionally substituted azetidine claim 2 , an optionally substituted oxetane claim 2 , an optionally substituted beta-lactam claim 2 , an optionally substituted tetrahydropyran claim 2 , an optionally substituted cyclopropyl claim 2 , an optionally substituted cyclobutyl claim 2 , an optionally substituted cyclopentyl claim 2 , or an optionally substituted cyclohexyl.711.-. (canceled)13. (canceled)15. (canceled)18. (canceled)20. (canceled)21. (canceled)22. (canceled)24. The compound or salt thereof of claim 1 , selected from compounds of Table 1 claim 1 , and pharmaceutically acceptable salts thereof.25. The compound or salt thereof of claim 1 , selected from compounds of Table 2 claim 1 , and pharmaceutically acceptable salts thereof.26. The compound or salt thereof of claim 1 , selected from compounds of Table 3 claim 1 , and pharmaceutically acceptable salts thereof.28. The compound or pharmaceutically acceptable salt thereof of claim 27 , wherein Rand Rare joined together with the atom to which they are attached to form an optionally substituted azetidine claim 27 , an optionally substituted oxetane claim 27 , an optionally substituted beta-lactam claim 27 , an optionally substituted tetrahydropyran claim 27 , an optionally ...

GYRASE INHIBITORS

Novel gyrase inhibitors and related compositions and methods are useful for impeding bacterial growth. Compounds of Formula (I), are disclosed: Formula (I), wherein Y is N or CH; Z is N or CR; Ris H, a substituted or unsubstituted hydrocarbyl residue (1-3C) containing 0-2 heteroatoms selected from O, S and N, or is an inorganic residue; L is O, S, NR, or CRR; Ris H or Calkyl; Rand Rare each independently H or Calkyl; Ris H, a hydrocarbyl residue (1-40C) containing 0-10 heteroatoms selected from O, S and N optionally substituted with an inorganic residue; Ris H, an inorganic residue, or a hydrocarbyl residue (1-30C) containing 0-12 heteroatoms selected from O, S and N and containing 0-10 inorganic residues, wherein Rand Rtogether may join to form a fused ring; and Ris selected from the group consisting of H, Calkyl, Calkenyl, Calkynyl, halo Calkyl, halo Calkenyl, halo Calkynyl, Chydroxyalkyl, Calkyl chloride, Calkenyl chloride, and Calkynyl chloride; or a pharmaceutically-acceptable salt, ester, or prodrug thereof. 2. The compound of claim 1 , whereinY is N; and{'sub': '2', 'L is O, S, NH, or CH.'}3. The compound of claim 1 , wherein Z is CR claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , halo claim 1 , unsubstituted Calkyl claim 1 , and Calkyl substituted with one or more substituents selected from the group consisting of ═O claim 1 , halo claim 1 , NH claim 1 , NHCH claim 1 , ≡N claim 1 , and Calkenyl claim 1 , wherein Rand Rtogether may join to form a fused ring.4. The compound of claim 1 , wherein Ris methyl claim 1 , C(O)CH claim 1 , C(O)NH claim 1 , CHOH claim 1 , CF claim 1 , CN claim 1 , CHF claim 1 , CHO claim 1 , acetyl claim 1 , Cl or Br.5. The compound of claim 1 , wherein Rcomprises at least one aryl or heteroaryl moiety.6. The compound of claim 1 , wherein the at least one aryl or a heteraryl moiety of Ris directly linked to L.7. The compound of claim 1 , wherein the at least one aryl or heteraryl moiety of Ris substituted ...

Benzisoxazoles and Azabenzisoxazoles as MGLUR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction

Benzisoxazole and azabenzisoxazole compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease state associated with glutamate dysfunction. 2. The method of claim 1 , wherein the mammal is a human.3. The method of claim 1 , wherein the dysfunction is Parkinson's disease.4. The method of claim 1 , wherein the dysfunction is schizophrenia claim 1 , psychosis claim 1 , “schizophrenia-spectrum” disorder claim 1 , depression claim 1 , bipolar disorder claim 1 , cognitive disorder claim 1 , delirium claim 1 , amnestic disorder claim 1 , anxiety disorder claim 1 , attention disorder claim 1 , obesity claim 1 , eating disorder claim 1 , or NMDA receptor-related disorder.5. The method of claim 1 , wherein the dysfunction is Parkinson's disease; anxiety; motor effects after alcohol consumption; neurogenic fate commitment and neuronal survival; epilepsy; or certain cancers claim 1 , for example claim 1 , medulloblastoma claim 1 , inflammation (for example claim 1 , multiple sclerosis) and metabolic disorders (for example claim 1 , diabetes) and taste enhancing associated with glutamatergic dysfunction and diseases in which mGluR4 receptor is involved.6. The method of claim 1 , wherein the mammal has been diagnosed with the dysfunction prior to the administering step.7. The method of claim 1 , further comprising the step of identifying a mammal having a need for treatment of the dysfunction.8. The method of claim 1 , wherein the endogenous ligand for mGluR4 potentiation is glutamate claim 1 , L-SOP claim 1 , or a neurotransmitter.925-. (canceled)28. The compound of claim 26 , wherein one X is CRwith Rbeing H claim 26 , and the other X is N.29. The compound of claim 26 , wherein Y is O ...

NOXIOUS ARTHROPOD CONTROL COMPOSITION AND HETEROCYCLIC COMPOUND

A noxious arthropod controlling composition comprising a heterocyclic compound represented by the formula (1) [wherein, Aand Arepresent ═C(R)—, nitrogen and so on, Rrepresents a halogen and so on, Rand Rrepresent optionally substituted C1 to C4 chain hydrocarbon group and so on, Rrepresents a hydrogen and so on, n represents 0 or 1] as an active ingredient has an excellent effect for controlling noxious arthropods. 2. The noxious arthropod controlling composition according to claim 1 , wherein the heterocyclic compound represented by the formula (1) is a heterocyclic compound wherein Ris hydrogen.3. The noxious arthropod controlling composition according to claim 1 , wherein the heterocyclic compound represented by the formula (1) is a heterocyclic compound wherein Ris hydrogen.4. The noxious arthropod controlling composition according to claim 1 , wherein the heterocyclic compound represented by the formula (1) is a heterocyclic compound wherein Ris hydrogen.5. The noxious arthropod controlling composition according to claim 1 , wherein the heterocyclic compound represented by the formula (1) is a heterocyclic compound wherein Ris a C1 to C6 chain hydrocarbon group optionally substituted with at least one selected from group X claim 1 , —OR claim 1 , —S(O)R claim 1 , —NRR claim 1 , —NRC(O)R claim 1 , —NRCOR claim 1 , —C(O)R claim 1 , —C(NOR)R claim 1 , —COR claim 1 , —CONRR claim 1 , —CONRNRR claim 1 , a cyano group claim 1 , a nitro group claim 1 , a halogen claim 1 , or hydrogen claim 1 ,{'sup': 7', '8', '7', '7', '9, 'sub': 'm', 'Rand Rare the same or different, and each are a C1 to C6 chain hydrocarbon group optionally substituted with at least one selected from group X or hydrogen (wherein when m in —S(O)Ris 1 or 2, Rrepresents a C1 to C6 chain hydrocarbon group optionally substituted with at least one selected from group X), and Ris a C1 to C6 chain hydrocarbon group optionally substituted with at least one selected from group X.'}6. The noxious arthropod ...

2,4-DIARYL - SUBSTITUTED [1,8] NAPHTHYRIDINES AS KINASE INHIBITORS FOR USE AGAINST CANCER

The present invention relates to novel [1,8]naphthyridine derivatives of formula (I) and to the use of such compounds in which the inhibition, regulation and/or modulation of signal transduction by ATP consuming proteins like kinases plays a role, particularly to inhibitors of TGF-beta receptor kinases, and to the use of such compounds for the treatment of kinase-induced diseases, in particular for the treatment of tumors. 2. Compound according to claim 1 , with the further proviso that Wdenotes N and/or Z excludes N═C claim 1 , i.e. Z denotes C═C claim 1 , N(R)CO claim 1 , NR claim 1 , C═N claim 1 , O claim 1 , CON(R) claim 1 , S claim 1 , CH or N═N claim 1 ,and the physiologically acceptable salts, solvates, stereoisomers and tautomers thereof, including mixtures thereof in all ratios.3. Compound according to claim 1 , wherein Z is selected from the group consisting of:(a) C═C, or{'sup': '4', '(b) N(R)CO, or'}{'sup': '4', '(c) NR, or'}(d) C═N, or(e) O, or{'sup': '4', '(f) CON(R),'}and preferably is C═C,and the physiologically acceptable salts, solvates, stereoisomers and tautomers thereof, including mixtures thereof in all ratios.6. Compound according to claim 1 , wherein{'sup': '2', 'sub': n', '2', 'n', 'n', 'n', 'n', 'n', 'n', '3, 'Ris absent or denotes H, A, Hal, —(CYY)—OY, NO, —(CYY)—NYY, —(CYY)-Het, —O—(CYY)-Het, —O—(CYY)—OY, —O—(CYY)—NYY, NY—(CYY)—NYY, NY—COY or a monocyclic heteroaryl having 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 C atoms and 1, 2, 3, 4 or 5 N, O and/or S atoms, where the monocyclic heteroaryl can be independently substituted by at least one substituent selected from the group consisting of Y, Hal, CN, CFor OY, and the physiologically acceptable salts, solvates, stereoisomers and tautomers thereof, including mixtures thereof in all ratios.'}10. A method for inhibiting ATP consuming proteins claim 1 , preferably TGF-beta receptor kinase claim 1 , RON claim 1 , TAK1 claim 1 , PKD1 claim 1 , MINK1 claim 1 , SAPK2-alpha claim 1 , SAPK2-beta and/or ...

NOVEL CONDENSED PYRIDINE OR CONDENSED PYRIMIDINE DERIVATIVE, AND MEDICINAL AGENT COMPRISING SAME

The present invention relates to provision of a novel compound that has an activity of promoting insulin secretion from pancreatic β cells and thus is useful as a prophylaxis and/or therapeutic agent for diseases caused by hyperglycemia such as diabetes mellitus, and 3. The compound of claim 1 ,which is selected from the following compound group, or a salt thereof, or a solvate of the compound or the salt:tert-butyl 4-(4-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}furo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate;7-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-d]pyrimidine-4-amine;7-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-d]pyrimidine-4-amine;N-[2-fluoro-4-(methylsulfonyl)phenyl]-7-[1-(5-fluoropyrimidin-2-yl)piperidin-4-yl]furo[3,2-d]pyrimidine-4-amine7-[1-(5-bromopyrimidin-2-yl)piperidin-4-yl]-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-d]pyrimidine-4-amine;N-[2-fluoro-4-(methyl sulfonyl)phenyl]-7-{1-[5-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}furo[3,2-d]pyrimidine-4-amine;benzyl 4-(4-[2-fluoro-4-(methylsulfonyl)phenyl]amino}furo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate;isopropyl 4-(4-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}furo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate;ethyl 4-(4-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}furo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate;7-(1-{[3,5-bis(trifluoromethyl)phenyl]sulfonyl}piperidin-4-yl)-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-d]pyrimidine-4-amine;7-[1-(cyclopropylsulfonyl)piperidin-4-yl]-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-c]pyrimidine-4-amine;7-[1-(cyclohexylsulfonyl)piperidin-4-yl]-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-d]pyrimidine-4-amine;N-[2-fluoro-4-(methylsulfonyl)phenyl]-7-[1-(thiophen-2-ylsulfonyl)piperidin-4-yl]furo[3,2-d]pyrimidine-4-amine;N-[2-fluoro-4-(methylsulfonyl)phenyl]-7-{1-[(4-methoxyphenyl)sulfonyl]piperidin-4-yl}furo[3,2-d]pyrimidine-4-amine;7-[1-(butylsulfonyl) ...

NOVEL FUSED PYRIMIDINE DERIVATIVES FOR INHIBITION OF TYROSINE KINASE ACTIVITY

The present invention relates to a novel fused pyrimidine derivative having an inhibitory activity for tyrosine kinases, and a pharmaceutical composition for preventing or treating cancers, tumors, inflammatory diseases, autoimmune diseases, or immunologically mediated diseases comprising same as an active ingredient. 3. The compound of claim 1 , wherein the compound of formula (I) is selected from the group consisting of:N-(3-(2-(2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino)thieno[3,2-d]pyrimidin-4-yloxy)phenyl)acrylamide;N-(3-(2-(4-(4-methylpiperazin-1-yl)phenylamino)thieno[3,2-d]pyrimidin-4-yloxy)phenyl)acrylamide;N-(3-(2-(4-(4-tert-butyl-piperazin-1-yl)-phenylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(4-(4-(2-fluoro-ethyl)-piperazin-1-yl)-phenylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(4-(4-(2,2,2-trifluoro-ethyl)-piperazin-1-yl)-phenylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(4-(4-(2-methoxy-ethyl)-piperazin-1-yl)-phenylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(4-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-phenylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(4-(4-hydroxy-4-methyl-piperazin-1-yl)-phenylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(4-(3,4,5-trimethyl-piperazin-1-yl)-phenylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(4-(5-methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-phenylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(2-methoxy-4-(1-methyl-piperidin-4-yl)-phenylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(2-methoxy-4-(1-methyl-piperidin-3-yl)-phenylamino)-thieno[3,2-d]pyrimidin-4-yloxy)-phenyl)-acrylamide;N-(3-(2-(3-fluoro-4-(4-methylpiperazin-1-yl)phenylamino)thieno[3,2-d]pyrimidin-4-yloxy)phenyl)acrylamide;Diethyl(4-((4-(3- ...

NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A

The present invention relates to novel compounds of the formula I which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders. 3. The compound of claim 1 , where Xis selected from O claim 1 , S claim 1 , —X═C(R)— claim 1 , where C(R) is bound to the carbon atom which carries R.4. The compound of claim 1 , where A is selected from A claim 1 , A claim 1 , Aand A.5. The compound of claim 1 , where Xis C—R.6. The compound of claim 5 , where Ris hydrogen or Y-Cyc.7. The compound of claim 1 , where Xis N.8. The compound of claim 1 , where Xis CH.9. The compound of claim 1 , where Xis S.10. The compound of claim 1 , where Xis O.11. The compound of claim 1 , where Xis C(R)═C(R).12. The compound of claim 1 , where Xis N═(CR).13. The compound of claim 11 , where Ris hydrogen or Y-Cyc3.14. The compound of claim 1 , where Xis N═C(R).15. The compound of claim 11 , where Ris hydrogen.16. The compound of claim 1 , where Ris a radical Y-Cyc.17. The compound of claim 1 , where Ris selected from the group consisting of hydrogen claim 1 , fluorine claim 1 , C-C-alkyl claim 1 , C-C-fluoroalkyl claim 1 , C-C-alkoxy claim 1 , C-C-fluoroalkoxy claim 1 , cyclopropyl claim 1 , optionally substituted by 1 claim 1 , 2 or 3 methyl groups claim 1 , and fluorinated cyclopropyl.18. The compound of claim 17 , where Ris hydrogen.19. The compound of claim 1 , where A is A.20. The compound of claim 19 , where R claim 19 , Rare selected from hydrogen and fluorine.21. The compound of claim 19 , where Rand Rare claim 19 , independently of each other claim 19 , selected from the group consisting of hydrogen claim 19 , fluorine and methyl.22. The compound of claim 1 , where A is A.23. The compound of claim 1 , where A is ...

NOVEL FUSARISETIN COMPOUNDS, AND USE THEREOF

The present invention relates to novel fusarisetin compounds separated from sp. FN080326 and having an anticancer activity, and to the use thereof. In detail, novel fusarisetin compounds separated and purified from sp. FN080326, which is in turn separated from a soil sample, have an inhibitory activity on the proliferation and transfer of cancer cells such as breast cancer cells, liver cancer cells or myeloid leukemic cells. Therefore, the compounds can be effectively used for anticancer compositions containing the compounds as active ingredients. 4Fusarium. The compound or the pharmaceutically acceptable salts thereof according to claim 1 , wherein the fusarisetin compound is separated from the fungus sp. FN080326.5. A composition for treatment of cancer comprising the compound or the pharmaceutically acceptable salts thereof of .6. The composition according to claim 5 , wherein the cancer is breast cancer claim 5 , liver cancer claim 5 , or myeloid leukemia.78-. (canceled)9. A method for producing the compound of comprising the following steps:{'i': 'Fusarium', '1) culturing sp. FN080326 strain; and'}2) separating fusarisetin compounds from the culture product of the strain obtained in step 1).10Fusarium. A fungus strain sp. FN080326 producing the compound of which has been deposited under the Accession No. of KCTC11985BP.11. A method for treating or preventing cancer comprising: administering a pharmaceutically effective dose of the compound or the pharmaceutically acceptable salts thereof of to a subject having cancer.1214-. (canceled) 1. Field of the InventionThe present invention relates to a fungus having an anticancer activity which is separated from a soil sample, to compounds having an inhibitory activity on the proliferation and metastasis of cancer cells which are produced from the said fungus, to anticancer compositions comprising the said compounds as active ingredients, and methods for the separation of the said compounds.2. Description of the Related ...

Tricyclic Compounds and Methods of Making and Using Same

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.

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.

FUROPYRIDINYL-SUBSTITUTED 1,4-DIHYDROPYRIDINE DERIVATIVES AND METHODS OF USE THEREOF

This invention relates to novel 4-(furo[3,2-c]pyridin-2-yl)-1,4-dihydropyridine derivatives having protein tyrosine kinase inhibitory activity, to a process for the manufacture thereof and to the use thereof for the treatment of c-Met-mediated diseases or c-Met-mediated conditions, particularly cancer and other proliferative disorders. 5. (canceled)6. (canceled)7. (canceled)8. A pharmaceutical composition comprising a compound as defined in claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate and/or solvate thereof claim 1 , and a pharmaceutically acceptable excipient.9. The pharmaceutical composition of further comprising one or more additional therapeutic agents.10. The pharmaceutical composition of claim 9 , wherein the additional therapeutic agent is an anti-tumor agent.11. (canceled)12. A method of treating or preventing a cell proliferative disorder in a mammal claim 1 , comprising administering to a mammal in need thereof a therapeutically effective amount of a compound as defined in .13. The method of claim 12 , wherein the cell proliferative disorder is cancer.14. The method of claim 13 , wherein the cancer is a cancer of the breast claim 13 , respiratory tract claim 13 , brain claim 13 , reproductive organs claim 13 , digestive tract claim 13 , urinary tract claim 13 , eye claim 13 , liver claim 13 , skin claim 13 , head or neck claim 13 , thyroid claim 13 , parathyroid claim 13 , or a distant metastasis of a solid tumor.15. The method of claim 13 , wherein the compound is administered in conjunction with surgery or radiation therapy.16. A method of treating or preventing a cell proliferative disorder in a mammal claim 8 , comprising administering to a mammal in need thereof a therapeutically effective amount of a pharmaceutical composition as defined in .17. The method of claim 16 , wherein the cell proliferative disorder is cancer.18. The method of claim 17 , wherein the cancer is a cancer of the breast claim 17 , respiratory tract claim 17 ...

1-Aryl or 1- Heteroaryl-Pyrido(B)indoles and Uses Thereof

Provided are 1-aryl or 1-heteroaryl substituted beta-carboline compounds or indole analogs thereof having the structure: 2. The substituted β-carboline compound of claim 1 ,wherein X is NH;{'sup': '1', 'Ris 1-naphthyl optionally substituted with Br or F; and'}{'sup': 2', '3', '4', '5', '6', '7, 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '2', '1', '4, 'R, R, R, R, R, and Rare independently H, OH, halogen, CN, C-Calkyl, C-Calkoxy, C-Chaloalkoxy, —C(O)OC-Cester, —(C-C)—SO—NH—(C-C) sulfonamide, or phenyl;'}{'sup': 5', '6', '7', '2', '3', '4', '5', '6', '7', '2', '3', '4', '5', '6', '7, 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '2', '1', '4, 'wherein, when one of R, R, or Ris C-Calkoxy, then R, R, R, R, R, and Rare independently H, OH, halogen, CN, C-Chaloalkoxy, —C(O)OC-Cester, —C-C—SO—NH—C-Csulfonamide, or phenyl such that at least two of R, R, R, R, R, and Rare other than H.'}3. The substituted β-carboline compound of claim 1 ,wherein X is NH;{'sup': '1', 'Ris 1-dihydroacenaphthenyl optionally substituted with Br or F; and'}{'sup': 2', '3', '4', '5', '6', '7, 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '2', '1', '4, 'R, R, R, R, R, and Rare independently H, OH, halogen, CN, C-Calkyl, C-Calkoxy, phenyl, C-Chaloalkoxy, —C(O)OC-Cester, —(C-C)—SO—NH—(C-C) sulfonamide, or phenyl.'}4. The substituted β-carboline compound of claim 1 ,{'sub': '3', 'wherein X is N—CH, S, or O;'}{'sup': '1', 'Ris 1-naphthyl or 1-dihydroacenaphthenyl each optionally substituted with Br or F; and'}{'sup': 2', '3', '4', '5', '6', '7, 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '2', '1', '4, 'R, R, R, R, R, and Rare independently H, OH, halogen, CN, C-Calkyl, C-Calkoxy, phenyl, C-Chaloalkoxy, —C(O)OC-Cester, —C-C—SO—NH—C-Csulfonamide or phenyl.'}5. A pharmaceutical composition comprising the substituted β-carboline compound of and a pharmaceutically effective carrier.6. A method for inhibiting proliferation of cells associated with a cell proliferative ...

Gonadotropin Releasing Hormone Receptor Antagonist, Preparation Method Thereof And Pharmaceutical Composition Comprising The Same

Disclosed are compounds useful as gonadotrophin-releasing hormone (“GnRH”) receptor antagonist. 4. The compound according to claim 1 , selected from the group consisting of:3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-5-[4-(2-methoxy-phenyl)-piperazin-1-yl]-6-methyl-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-5-[4-(3-methoxy-phenyl)-piperazin-1-yl]-6-methyl-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-5-(4-benzyl-piperazin-1-yl)-1-(2,6-difluoro-benzyl)-6-methyl-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-5-[4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,6-difluoro-benzyl)-6-methyl-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-5-[4-(2-fluoro-benzyl)-piperazin-1-yl]-6-methyl-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-6-methyl-5-(4-pyridin-2-yl-piperazin-1-yl)-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-5-[4-(3-fluoro-benzyl)-piperazin-1-yl]-6-methyl-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-6-methyl-5-[4-(4-trifluoromethyl-benzyl)-piperazin-1-yl]-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-5-(4-benzoyl-piperazin-1-yl)-1-(2,6-difluoro-benzyl)-6-methyl-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-6-methyl-5-(4-methyl-piperidin-1-yl)-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-6-methyl-5-(3-trifluoromethyl-piperidin-1-yl)-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-6-methyl-5-(3-methyl-piperidin-1-yl)-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-6-methyl-5-(4-phenyl-piperazin-1-yl)-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-5-(4-cyclohexylmethyl-piperazin-1-yl)-1-(2,6-difluoro-benzyl)-6-methyl-1H-pyrimidine-2,4-dione;3-((R)-2-amino-2-phenyl-ethyl)-1-(2,6-difluoro-benzyl)-5-[4-(2-fluoro-phenyl)-piperazin-1-yl]-6- ...

Heterocyclic compound and use thereof

The present invention aims to provide a compound having a PDE inhibitory action and useful as a medicament for the prophylaxis or treatment of schizophrenia and the like. A compound represented by the formula (1 x ): wherein each symbol is as described in the DESCRIPTION, or the formula (1): W 1 —W 2   (1) wherein each symbol is as described in the DESCRIPTION, or a salt thereof.

FURO[3, 2-B] PYRR0L-3-ONES AS CATHESPIN S INHIBITORS

A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, 141-. (canceled)43. A method of inhibiting a cysteine proteinase in a cell claim 42 , said method comprising contacting said cell with the composition of .44. A method of inhibiting a cysteine proteinase in a subject claim 42 , said method comprising administering to the subject a pharmacologically effective amount of the composition of .45. A method according to wherein the cysteine proteinase is a CAC1 cysteine proteinase.46. A method according to wherein the CAC1 cysteine proteinase is cathepsin S.47. A method of treating a disease selected from rheumatoid arthritis claim 42 , multiple sclerosis claim 42 , myasthenia gravis claim 42 , transplant rejection claim 42 , diabetes claim 42 , Sjogrens syndrome claim 42 , Grave's disease claim 42 , systemic lupus erythematosis claim 42 , osteoarthritis claim 42 , psoriasis claim 42 , idiopathic thrombocytopenic purpura claim 42 , allergic rhinitis claim 42 , asthma claim 42 , atherosclerosis claim 42 , obesity claim 42 , chronic obstructive pulmonary disease and chronic pain in a subject claim 42 , said method comprising administering to the subject a pharmacologically effective amount of the composition of .48. A method of validating a known or putative cysteine proteinase as a therapeutic target claim 42 , the method comprising:{'claim-ref': {'@idref': 'CLM-00042', 'claim 42'}, '(a) assessing the in vitro binding of the composition of to an isolated or known putative cysteine proteinase, providing a measure of potency; and optionally, one or more of the steps of{'claim-ref': {'@idref': 'CLM-00042', 'claim 42'}, '(b) assessing the binding of the composition of to closely related homologous proteinases of the target and general housekeeping proteinases (e.g. trypsin) to provide a measure of selectivity;'}{'claim-ref': {'@idref': 'CLM-00042', 'claim 42'}, '(c) monitoring a cell ...

NEW SELECTIVE CCR2 ANTAGONISTS

The present invention relates to novel and selective antagonists for CCR2 (CC chemokine receptor 2) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD as well as pain. 2. The compound of claim 1 ,{'sub': 4', '5', '4', '5', '4', '5, 'wherein Z denotes a five-, or six-membered ring formed by a —C-C-alkylene, wherein the —C-C-alkylene is bi-valently linked to the N atom, and in which one carbon center of the —C-C-alkylene may optionally be replaced by 1 hetero atom selected from N, and O,'}{'sub': 3', '4', '1', '3', '2', '1', '3', '2', '1', '3', '2', '1', '3, 'and wherein the ring Z is further bi-valently substituted on two neighbouring ring atoms, such that an annellated ring is formed by a group selected from among —C-C-alkylene, in which one carbon center may optionally be replaced by 1 hetero atom selected from O, and N, and wherein the bivalent group is optionally substituted by one or more groups selected from —N(C-C-alkyl)-SO—C-C-alkyl, —NH—SO—C-C-alkyl, and —SO—C-C-alkyl.'}7. The compound of claim 1 , wherein Ris a group selected from among —CH claim 1 , —OCH claim 1 , and -cyclopropyl.8. The compound of claim 1 , wherein Ris selected from among —H claim 1 , —CH claim 1 , —OCH claim 1 , —CF claim 1 , and -cyclopropyl.9. The compound of claim 1 , wherein Ris selected from among —H claim 1 , —CH claim 1 , —CH claim 1 , —O—CH claim 1 , —O—CH claim 1 , —F claim 1 , —CF claim 1 , and —OCF.10. The compound of claim 1 , wherein A denotes —NH-L-Rand Lis a bond.11. The compound of claim 1 , wherein G and E are N.12. The compound of claim 1 , wherein n is 2.13. A method for the treatment of an inflammatory disease of the respiratory tract selected from chronic obstructive pulmonary disease claim 1 , asthma claim 1 , and cystic fibrosis claim 1 , comprising administering to a patient in need thereof a therapeutic amount of a compound according to or a pharmacologically acceptable salt thereof.14 ...

NEW COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF

The present invention relates to compounds of formula I, 2. The compound according to claim 1 , wherein Ris 2-fluoro-2-methylpropyl or (1-trifluoromethylcyclopropyl)methyl.8. A pharmaceutical composition comprising a compound according to and an inert carrier or diluent.9. A method for treating diseases or conditions which are mediated by activating the G-protein-coupled receptor GPR119 in a patient in need thereof claim 1 , the method comprising administering to the patient a pharmaceutically effective amount of a compound according to .10. The method according to claim 1 , wherein the disease or condition which are mediated by activating the G-protein-coupled receptor GPR119 is diabetes claim 1 , obesity claim 1 , or dyslipidemia. The present invention relates to new compounds of formula Iwherein R, L, L, X, A and n are defined as hereinafter, to processes for preparing these compounds, to their use as modulators of the G-protein-coupled receptor GPR119, to methods for their therapeutic use, in particular in diseases and conditions mediated by the modulation of the G-protein-coupled receptor GPR119, and to pharmaceutical compositions comprising them.Diabetes mellitus is a serious metabolic disease which affects more than 100 million people worldwide. In the USA there are more than 12 million diabetics with 600,000 new cases diagnosed every year. The prevalence of diabetes mellitus is increasing, resulting in a high frequency of complications and a substantial impairment of quality of life and life expectancy. Because of diabetes-associated microvascular complications, in the industrialised countries type 2 diabetes is currently the most common cause of adult-onset loss of vision, renal insufficiency and amputations. In addition, type 2 diabetes is associated with a two- to five-fold increase in the risk of cardiovascular disease.The UKPDS study (United Kingdom Prospective Diabetes Study) showed that intensive treatment with common therapeutic agents, e.g. ...

Cannabinoid Agonists

The present disclosure relates to compounds useful as agonists of the cannabinoid receptors. The disclosure also provides pharmaceutically acceptable compositions comprising the compounds of the disclosure and methods of using the compositions in the treatment of various disorders, either alone or in combination therapy. The compounds of the invention have Formula (I).

APOPTOSIS PROMOTERS

Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member. 19-. (canceled)10. A compound , or a therapeutically acceptable salt thereof , wherein the compound is selected from the group consisting of:N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(5,6-dihydro-1(4H)-pyrimidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(2,4-dimenthyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-methyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)oxy)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;4-(((1R)-3-(bis(2-methoxyethyl)amino)-1 ...

N-heteroaryl compounds

This invention relates to certain N-heteroaryl compounds that are generally useful as medicaments, more specifically as medicaments for animals. The medicament can preferably be used for the treatment of helminth infections and the treatment of parasitosis, such as caused by helminth infections. This invention also relates to uses of the compounds to make medicaments and treatments comprising the administration of the compounds to animals in need of the treatments. This invention also relates to novel N-heteroaryl compounds and the preparation of said compounds. Moreover this invention relates to pharmaceutical compositions and kits comprising the compounds.

FUSED HETEROCYCLIC DERIVATIVES AS S1P MODULATORS

The present invention relates to a fused heterocyclic derivative of the formula (I) 2. The compound of claim 1 , wherein 'a group selected from a (3-6C)cycloalkyl group and a (8-10C)bicyclic group wherein the group is optionally substituted with a halogen atom, (1-4C)alkyl, and a phenyl group wherein the phenyl group is optionally substituted with at least one substituent independently selected from a halogen atom, cyano, (1-4C)alkyl, (1-4C)alkoxy, a trifluoromethyl, and a trifluoromethoxy;', 'R1 is selected from'}{'sub': '2', 'W is selected from a bond, —O—, —CO—, —S—, —SO—, —SO—, —NH—, —CH═CH—, —C≡C—, and a trans-cyclopropylene;'}n is an integer from 0 to 4; andR2 is selected from H and at least one substituent independently selected from a halogen atom, (1-4C)alkyl optionally substituted with at least one fluoro and (1-4C)alkoxy optionally substituted with at least one fluoro atom.5. The compound of claim 1 , wherein Y is O.6. The compound of claim 1 , wherein R4 is selected from —(CH)—COOH claim 1 , —(CH)—COOH claim 1 , —CH—CHCH—COOH claim 1 , —CH—C(CH)—COOH claim 1 , —CHCH—CH—COOH claim 1 , —CH—CF—COOH claim 1 , and 1 claim 1 ,3-cyclobutylene-COOH.7. The compound of claim 1 , wherein R1 is a phenyl group optionally substituted with at least one substituent independently selected from halogen claim 1 , cyano claim 1 , (1-4C)alkyl optionally substituted with at least one halogen atom claim 1 , (1-4C)alkoxy optionally substituted with at least one halogen atom claim 1 , amino claim 1 , dimethylamino claim 1 , and (3-6C)cycloalkyl optionally substituted with a phenyl group wherein the phenyl group is optionally substituted with a substituent selected from (1-4C)alkyl and a halogen atom.8. The compound of claim 7 , wherein R1 is a phenyl group optionally substituted with at least one substituent independently selected from a halogen atom claim 7 , cyano claim 7 , (1-4C)alkyl claim 7 , (1-4C)alkoxy claim 7 , a trifluoromethyl claim 7 , and a trifluoromethoxy.9. The ...

FUROPYRIDINE DERIVATIVES

Compounds of the formula I 2. Compounds according to in which{'sup': 1', '4, 'sub': 2', 'n', '2', 'n, 'Hetdenotes furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, pyridazinyl, pyrazinyl, quinolyl, isoquinolyl, benzimidazolyl, benzotriazolyl, indolyl, benzo-1,3-dioxolyl, 2,3-dihydro-benzo[1,4]dioxinyl, indazolyl or benzothiadiazolyl, each of which is unsubstituted or mono-, di- or trisubstituted by Het, A, benzyl, (CH)OH and/or (CH)OA,'}and pharmaceutically acceptable solvates, salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.3. Compounds according to in which{'sup': 2', '4', '4', '4, 'sub': 2', 'n', '2', 'n', '2', 'n', '2', 'n', '2', 'p', '2', 'p', '2', 'p', '2', 'p', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'p', '2', '2', '2', '2, 'Hetdenotes piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, pyridazinyl, pyrazinyl, quinolyl, isoquinolyl, benzimidazolyl, benzothiophenyl, benzotriazolyl, indolyl, indolinyl, benzo-1,3-dioxolyl, 2,3-dihydro-benzo[1,4]dioxinyl, 1,3-dihydro-indolyl, 1,3-dihydrobenzimidazolyl, dihydropyranyl, 3,4-dihydro-2H-pyrano[2,3-b]pyridinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, furopyridinyl, indazolyl, benzo[1,4]oxazinyl, pyrido[3,2-b][1,4]oxazinyl or benzothiadiazolyl, each of which is unsubstituted or mono-, di- or trisubstituted by Hal, (CH)Het, NH(CH)Het, OHet, A, (CH)OH, (CH)OA, (CH)CH(OH)(CH)OH, (CH)CH(OH)(CH)OA, (CH)COOA, phenyl, benzyl, CHO, COA, (CH)NH, (CH)NHA, (CH)NA, NH(CH)NH, CN, NHSOA, NASOA, SOA and/or ═O,'}and pharmaceutically acceptable solvates, salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.4. Compounds according to in which{'sup': 3', '3, 'sub': 2', 'n', ...

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.

Protease inhibitors

Compounds of the formula II: wherein R 1 and R 2 are independently H, F or CH 3 ; or R 1 forms an ethynyl bond and R 2 is H or C 3 -C 6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF 3 , OMe or halo; R 3 is C 1 -C 3 alkyl or C 3 -C 6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R 3 is C 3 -C 6 cycloalkyl it may alternatively be gem substituted with fluoro; R 4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A 1 is CH or N, A 2 is CR 6 R7 or NR 6 , provided at least one of A 1 and A 2 comprises N; R 6 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkyl-O—C 1 -C 3 alkyl, or when A 2 is C, R 6 can also be C 1 -C 4 alkoxy or F; R 7 is H, C 1 -C 4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

PYRROLIDINONE CARBOXAMIDE DERIVATIVES

Pyrrolidinone carboxamide compounds are provided that are useful for inhibiting the binding of ligands to the ChemR23 receptor. 3. A compound of claim 1 , wherein Ris methyl.4. A compound of claim 1 , wherein Ris methyl claim 1 , and Ris H or Calkyl.5. A compound of claim 1 , wherein Ris H or Calkyl claim 1 , Ris methyl claim 1 , and Ris H or Calkyl.6. A compound of claim 1 , wherein Ris CF.7. A compound of claim 1 , wherein Ris methyl and Ris CF.9. A compound of claim 8 , wherein Ris selected from the group consisting of —NRRand RRN—Calkyl.10. A compound of claim 9 , wherein Ris RRN—Calkyl.11. A compound of claim 9 , wherein Ris —NRR.12. A compound of claim 8 , wherein Rand Rare each methyl.13. A compound of claim 12 , wherein Ris selected from the group consisting of CF claim 12 , CN and cyclopropyl.14. A compound of claim 8 , wherein Ris mono- or di-(Calkyl)amino-Calkyl claim 8 , and Ris methyl.15. A compound of claim 14 , wherein Ris di(Calkyl)aminomethyl.16. A compound of claim 8 , wherein Rand Rare each methyl.18. A compound of claim 17 , wherein Ris H claim 17 , and Rand Rare each methyl.19. A compound of claim 18 , wherein Ris CF.21. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.221111111111111111111111111111111. The pharmaceutical composition of claim 21 , wherein the compound is a compound provided in claim 21 , B claim 21 , C claim 21 , D claim 21 , E claim 21 , F claim 21 , G claim 21 , H claim 21 , I claim 21 , J claim 21 , K claim 21 , L claim 21 , M claim 21 , N claim 21 , O claim 21 , P claim 21 , Q claim 21 , R claim 21 , S claim 21 , T claim 21 , U claim 21 , V claim 21 , W claim 21 , X claim 21 , Y claim 21 , Z claim 21 , AA claim 21 , BB claim 21 , CC claim 21 , DD claim 21 , EE and FF.23. A method of treating a disease or disorder in a mammal claim 1 , said method comprising administering to said subject a therapeutically effective amount of a compound of claim 1 , for a period of time ...

CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. 140-. (canceled)42. The carboxamide compound as claimed in claim 41 , in which m is 0 or 1 and claim 41 , when m=1 claim 41 , R* is selected from OH claim 41 , F claim 41 , Cl claim 41 , CN claim 41 , CF claim 41 , C-C-alkyl which is unsubstituted or may have 1 claim 41 , 2 or 3 substituents R claim 41 , or C-C-haloalkyl claim 41 , C-C-alkoxy claim 41 , C-C-haloalkoxy and C-C-cycloalkyl.43. The carboxamide compound as claimed in claim 41 , in which X is a C(═O)—NRRradical.45. The carboxamide compound as claimed in claim 44 , in which X is C(O)—NH.46. The carboxamide compound as claimed in claim 41 , in which Ris selected from C-C-alkyl which may be partly or completely halogenated and/or have 1 claim 41 , 2 or 3 substituents R claim 41 , C-C-cycloalkyl-C-C-alkyl claim 41 , where the cycloalkyl moiety may have 1 claim 41 , 2 claim 41 , 3 or 4 radicals R claim 41 , phenyl-C-C-alkyl and hetaryl-C-C-alkyl claim 41 , where phenyl and hetaryl in the last 2 radicals mentioned may be unsubstituted or carry 1 claim 41 , 2 claim 41 , 3 or 4 identical or different radicals R.47. The carboxamide compound as claimed in claim 41 , in which Ris selected from OH claim 41 , F claim 41 , Cl claim 41 , NH claim 41 , CN claim 41 , CF claim 41 , —CHF claim 41 , O—CF claim 41 , O—CHF claim 41 , O—CHF claim 41 , C-C-alkyl claim 41 , C-C-cycloalkyl claim 41 , C-C-alkylamino claim 41 , C-C-dialkylamino claim 41 , pyrrolidinyl claim 41 , piperidinyl claim 41 , morpholinyl claim 41 , imidazolyl claim 41 , C-C-alkoxy claim 41 , C-C-alkoxy-C-C-alkyl claim 41 , CONRR claim 41 , SONRR claim 41 , —NH—SO—R claim 41 , —(CH)—NRR claim 41 , NH—CO—R claim ...

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. 2. The compound of wherein Ris COH claim 1 , Ris hydrogen claim 1 , and Z is O.3. The compound of wherein J is a bond.4. The compound of wherein A is phenyl.5. The compound of wherein phenyl is substituted with one R.6. The compound of wherein phenyl is substituted with two R.7. The compound of wherein phenyl is substituted with three R.8. The compound of wherein R is selected from F claim 4 , Cl claim 4 , Br claim 4 , I claim 4 , or C-Calkyl.9. The compound of wherein A is benzofuran.10. The compound of wherein benzofuran is substituted with one R.11. The compound of wherein X is B selected from benzoxazole claim 4 , benzothiazole claim 4 , benzimidazole claim 4 , pyrazolopyridine claim 4 , imidazopyridine claim 4 , benzoxadiazole claim 4 , benzothiadiazole claim 4 , and benzotriazole wherein B is optionally substituted with at least one R.12. The compound of wherein B is benzoxazole.13. The compound of wherein B is benzothiazole.14. The compound of wherein B is pyrazolopyridine.15. The compound of wherein B is benzothiadiazole.16. The compound of wherein R is selected from F claim 11 , Cl claim 11 , Br claim 11 , I claim 11 , —CN claim 11 , —NO claim 11 , —CF claim 11 , —OH claim 11 , —OR claim 11 , —OCF claim 11 , C-Calkylenealkyne claim 11 , C-Calkyl claim 11 , C-Ccycloalkyl claim 11 , C-Cheteroalkyl claim 11 , C-Chaloalkyl claim 11 , tetrazolyl claim 11 , C-Cheterocycloalkyl claim 11 , and phenyl.17. The compound of wherein R is selected from F claim 16 , Cl claim 16 , Br claim 16 , and I.19. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable diluent claim ...

Compounds

A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, 3. A compound according to wherein one of Rand Ris H claim 1 , and the other is selected from methyl claim 1 , ethyl claim 1 , propyl claim 1 , iso-propyl claim 1 , tert-butyl claim 1 , cyclopropyl claim 1 , cyclopropylmethyl claim 1 , iso-propylmethyl claim 1 , tert-butylmethyl claim 1 , CHOH claim 1 , CHOMe claim 1 , CHOCHPh claim 1 , CHPh claim 1 , CHF and CHF.4. A compound according to wherein one of Rand Ris H claim 1 , and the other is C-alkyl.5. A compound according to wherein one of Rand Ris H claim 1 , and the other is selected from methyl claim 1 , ethyl claim 1 , iso-propyl and CHF.6. A compound according to wherein Ris selected from tert-butylmethyl claim 1 , iso-propyl methyl claim 1 , sec-butyl claim 1 , tert-butyl claim 1 , cyclopentyl and cyclohexyl.7. A compound according to wherein Ris cyclopentyl or tert-butyl.8. A compound according to wherein with respect to the definition of R:G is N;E is selected from O, S and NH;J and R are each independently selected from CH and N.9. A compound according to wherein with respect to the definition of R:G is N;J and R are both CH;E is S.10. A compound according to wherein Ris selected from 4-methylpiperazin-1-yl and 4-(2-methoxyethyl)piperazin-1-yl.12. A compound according to wherein Ris selected from methyl claim 1 , ethyl and propyl.13. A compound according to which is selected from the following:N—((S)-4-methyl-1-((3aS,6R,6aR)-6-methyl-3-oxodihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6aH)-yl)-1-oxopentan-2-yl)-4-(2-(4-methylpiperazin-1-yl)thiazol-4-yl)benzamideN—((S)-1-((3aS,6R,6aR)-6-ethyl-3-oxodihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6a H)-yl)-4-methyl-1-oxopentan-2-yl)-4-(2-(4-methylpiperazin-1-yl)thiazol-4-yl)benzamideN—((S)-4-methyl-1-oxo-1-((3aS,6R,6aR)-3-oxo-6-propyldihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6aH)-yl)pentan-2-yl)-4-(2-(4-methylpiperazin-1-yl)thiazol-4-yl)benzamideN—((S)-1-((3aS,6R,6aR)-6-isopropyl-3- ...

SUBSTITUTED 4-(SELENOPHEN-2(OR-3)-YLAMINO)PYRIMIDINE COMPOUNDS AND METHODS OF USE THEREOF

Selenophene compounds of formula (I) are described herein. In the compounds of Formula (I), ring A is a 6-membered aromatic fused ring, optionally containing one, two or three nitrogen atoms; a 5-membered heteroaromatic fused ring; or a mono- or bicyclic saturated heterocyclic fused ring having at least one ring member selected from the group consisting of N, O, S, SO and SO; Y in ring B is nitrogen or substituted carbon; X is NR, O, S, S(O), or S(O). R, R, R, R, and Rare defined in the specification. Selenophene compounds of formula (I) may be used in methods of treating cell proliferative disorders, particularly cancer. Pharmaceutical compositions containing selenophene compounds of formula (I) may be used for treatment, inhibition, or control of cancer. 2. A selenophene compound of formula (I) as claimed in claim 1 , wherein X is attached to the C2 carbon of the seleneophene ring.3. A selenophene compound of formula (I) as claimed in claim 1 , wherein X is attached to the C3 carbon of the seleneophene ring.4. A selenophene compound of formula (I) as claimed in claim 1 , wherein X is NRor O claim 1 , and wherein Ris selected from the group consisting of hydrogen claim 1 , amino claim 1 , C-alkyl claim 1 , and haloCalkyl.8. A selenophene compound of formula (VI) as claimed in claim 7 , wherein Z claim 7 , Z claim 7 , Z claim 7 , and Zare each C—R.9. A selenophene compound of formula (VI) as claimed in claim 7 , wherein Z claim 7 , Z claim 7 , Z claim 7 , and Zare independently selected from the group consisting of N and C—R claim 7 ,{'sup': 1', '2', '3', '4, 'with the proviso that at least one of Z, Z, Z, and Zis N.'}10. A selenophene compound of formula (VI) as claimed in claim 7 , wherein Z claim 7 , Z claim 7 , Z claim 7 , and Zare independently selected from the group consisting of N and C—R claim 7 ,{'sup': 1', '2', '3', '4, 'with the proviso that two of Z, Z, Z, and Zare N.'}11. A selenophene compound of formula (VI) as claimed in claim 7 , wherein Z claim 7 ...

Complement pathway modulators and uses thereof

The present invention provides a compound of formula I: 4. The compound of claim 1 , or salt or tautomer thereof claim 1 , wherein Ris absent.5. The compound of claim 1 , or salt or tautomer thereof claim 1 , wherein Ris hydrogen claim 1 , chloro or phenyl.6. The compound of claim 1 , or salt or tautomer thereof claim 1 , wherein Ris hydrogen.7. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris methyl.8. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris halogen claim 1 , C-Calkyl claim 1 , vinyl claim 1 , cyclopropyl claim 1 , C-Calkoxy claim 1 , hydroxyC-Calkyl claim 1 , C-CalkoxyC-Calkyl claim 1 , C-CalkoxyC-Calkoxy claim 1 , cyclopropylC-Calkoxy claim 1 , haloC-Calkoxy or S(O)C-Calkyl.9. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris C-Calkyl claim 1 , C-Calkoxy claim 1 , cyclopropyl claim 1 , bromo or difluoromethoxy.10. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris hydrogen claim 1 , methyl claim 1 , ethyl cyclopropyl or trifluoromethyl.11. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris hydrogen claim 1 , hydroxy claim 1 , methoxy claim 1 , amino claim 1 , mono- and di-methylamino or CHR; and{'sup': '7', 'sub': 3', '3', '2, 'Ris hydroxy, amino, N(H)CHor N(CH).'}12. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris methyl or trifluoromethyl;{'sup': 6', '7, 'sub': '2', 'Ris hydroxy, methoxy, amino, methylamino or CHR; and'}{'sup': '7', 'sub': 3', '3', '2, 'Ris hydroxy, amino, N(H)CHor N(CH).'}13. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein X is N; and Y is N(H).14. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein X is N; and Y is O.15. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein X is N; and Y is S.16. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein X is CH; and Y is N(H) claim 1 ...

Inhibitors of Hepatitis C Virus

A class of compounds that inhibit Hepatitis C Virus (HCV) is disclosed, along with compositions containing the compound, and methods of using the composition for treating individuals infected with HCV. 2. The compound of claim 1 , having an inhibitory activity with respect to HCV claim 1 , as measured by the concentration of the compound effective to produce a half-maximal inhibition of HCV1b replication (EC) in a 1b_Huh-Luc/Neo-ET cell line in culture claim 1 , of 1 mM or less.7. The compound of claim 6 , selected from the group consisting of compounds identified by ID NOS: B89 claim 6 , B96 claim 6 , B97 claim 6 , B125 claim 6 , B126 claim 6 , and B129.9. The compound of claim 5 , wherein Ris phenyl substituted with one or more Rsubstituents.10. The compound of claim 5 , where Ris 4-phenoxyphenyl and the phenoxy group is substituted with one or more Rsubstituents.15. The compound of claim 14 , having an inhibitory activity with respect to HCV claim 14 , as measured by the concentration of the compound effective to produce a half-maximal inhibition of HCV1b replication (EC) in a 1b_Huh-Luc/Neo-ET cell line in culture claim 14 , of 100 nM or less.17. The compound of claim 16 , selected from the group consisting of compounds identified by ID NOS: B5 claim 16 , B15 claim 16 , B20 claim 16 , B33 claim 16 , B35 claim 16 , B45 claim 16 , B67 claim 16 , B85 claim 16 , B92 claim 16 , B94 claim 16 , B107 claim 16 , B118 claim 16 , B120 claim 16 , B121 claim 16 , B127 claim 16 , B128 claim 16 , B130 claim 16 , B131 claim 16 , B132 claim 16 , B138 claim 16 , B139 claim 16 , B145 claim 16 , B148 claim 16 , B158 claim 16 , B163 claim 16 , B168 claim 16 , B169 claim 16 , B171 claim 16 , B187 claim 16 , B190 claim 16 , B191 claim 16 , B192 claim 16 , B196 claim 16 , B197 claim 16 , B198 claim 16 , B201 claim 16 , B207 claim 16 , B208 claim 16 , B212 claim 16 , B214 claim 16 , B218 claim 16 , B221 claim 16 , B226 claim 16 , B232 claim 16 , B233 claim 16 , B236 claim 16 , B237 ...

PROTEIN KINASE INHIBITORS

Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure: 2. A composition comprising the compound of in combination with a pharmaceutically acceptable excipient or carrier.3. A method for treating a protein kinase-mediated disease claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of the composition of .4. The method of claim 3 , wherein the protein kinase-mediated disease is an aurora-2 kinase-mediated disease claim 3 , a c-kit-mediated disease claim 3 , a PDGFR-a-mediated disease claim 3 , a c-ret-mediated disease or a c-met-mediated disease.5. The method of wherein the protein-kinase mediated disease is cancer.6. The method of wherein the cancer is a cancer of the pancreas claim 5 , breast claim 5 , ovary or colon.7. The method of claim 3 , further comprising administering to the subject one or more additional chemotherapeutic agents.8. The method of claim 7 , wherein the chemotherapeutic agent is selected from the group consisting of mitotic inhibitors claim 7 , alkylating agents claim 7 , anti-metabolites claim 7 , cell cycle inhibitors claim 7 , enzymes claim 7 , topoisomerase inhibitors claim 7 , biological response modifiers claim 7 , anti-hormones claim 7 , antiangiogenic agents claim 7 , anti-androgens claim 7 , platinum coordination complexes claim 7 , substituted ureas claim 7 , methylhydrazine derivatives claim 7 , adrenocortical suppressants claim 7 , hormone and hormone antagonists claim 7 , progestins claim 7 , estrogens claim 7 , antiestrogens claim 7 , androgens claim 7 , and aromatase inhibitors.9. The method of claim 7 , wherein the chemotherapeutic agent is a DNA-damaging agent.10. The method of claim 3 , further comprising administering radiation to the subject.11. A method for treating a cancer claim 2 , the method comprising administering to ...

Antiviral Drugs for Treatement or Prevention of Dengue Infection

Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by flavivirus is disclosed, i.e., including but not limited to, Dengue virus, West Nile virus, yellow fever virus, Japanese encephalitis virus, and tick-borne encephalitis virus. 2. The composition of claim 1 , wherein Ris ethyl.3. The composition of claim 1 , wherein Ris ethyl.4. The composition of claim 1 , wherein Ar is mono-substituted phenyl.5. The composition of claim 4 , wherein said mono-substituted phenyl is amido-phenyl.6. The composition of claim 5 , wherein said amido-phenyl is selected from the group consisting of isobutyramidophenyl claim 5 , p-[2-(4-oxo-4H-quinazolin-3-yl)-acetamido]-phenyl and p-[2-(4-oxo-4H-benzo[d][1 claim 5 ,2 claim 5 ,3]triazin-3-yl)-acetamido]-phenyl.7. The composition of claim 1 , wherein Ar is a di-substituted phenyl.8. The composition of claim 7 , wherein said di-substituted phenyl has one substituent as amido and the other one as methoxy.9. The composition of claim 8 , wherein said di-substituted phenyl is m-phenyl-acetamido-p-methoxy-phenyl.10. The composition of claim 8 , wherein di-substituted phenyl is m-(3-methyl-butyramido)-p-methoxy-phenyl.11. The compound of claim 1 , wherein the compound of Formula I is selected from the group consisting of N-(4-Diethylsulfamoyl-phenyl)-2-(4-oxo-4H-quinazolin-3-yl)-acetamide; N-(5-Diethylsulfamoyl-2-methoxy-phenyl)-isobutyramide; N-(4-Diethylsulfamoyl-phenyl)-2-(4-oxo-4H-benzo[d][1 claim 1 ,2 claim 1 ,3]triazin-3-yl)-acetamide; N-(4-Diethylsulfamoyl-phenyl)-2-(1 claim 1 ,3-dimethyl-2 claim 1 ,6-dioxo-1 claim 1 ,2 claim 1 ,3 claim 1 ,6-tetrahydro-purin-7-yl)-acetamide; N-(4-Diethylsulfamoyl-phenyl)-2-(4-oxo-4H- ...

Novel carboxylic acid derivatives, their preparation and use

Carboxylic acid derivatives where R—R 6 , X, Y and Z have the meanings stated in the description, and the preparation thereof, are described. The novel compounds are suitable for controlling diseases.

N-(IMIDAZOLIDIN-2-YLIDENE)-HETEROCYCLOPENTA[b]PYRIDINE DERIVATIVES AS MODULATORS OF ALPHA 2 ADRENERGIC RECEPTORS

The present invention relates to novel N-(imidazolidin-2-ylidene)-heterocyclo penta[b]pyridine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals. 2. The method according to claim 1 , wherein the disorder is a retinal disease selected from: age related macular degeneration claim 1 , wet macular degeneration claim 1 , dry macular degeneration claim 1 , geographic atrophy claim 1 , diabetic retinopathy claim 1 , diabetic macular edema claim 1 , tumors claim 1 , retinal vein occlusion claim 1 , ocular hypertension claim 1 , glaucoma claim 1 , retinitis pigmentosa and neuritis secondary to multiple sclerosis.3. The method according to claim 1 , wherein the disorder is a skin condition selected from: rosacea claim 1 , sunburn claim 1 , psoriasis claim 1 , acne rosacea claim 1 , menopause-associated hot flashes claim 1 , hot flashes resulting from orchiectomyatopic dermatitis claim 1 , photoaging claim 1 , seborrheic dermatitis claim 1 , acne claim 1 , allergic dermatitis claim 1 , redness of the skin claim 1 , telangiectasia of the face claim 1 , rhinophymia claim 1 , red bulbous nose claim 1 , acne-like skin eruptions claim 1 , burning or stinging sensation of the face claim 1 , irritated and bloodshot and watery eyes claim 1 , erythema of the skin claim 1 , cutenous hyperactivity with dilation of blood vessels of the skin claim 1 , Lyell's syndrome claim 1 , Stevens-Johnson syndrome claim 1 , erythema multiforme minor and erythema multiforme major.4. The method according to claim 1 , wherein the disorder is glaucoma claim 1 , elevated intraocular pressure claim 1 , ischemic neuropathies claim 1 , optic neuropathy claim 1 , pain claim 1 , visceral pain claim 1 , corneal pain claim 1 , headache pain claim 1 , migraine claim 1 , cancer pain claim 1 , back pain claim 1 , irritable bowel syndrome pain claim 1 , muscle pain and pain associated with diabetic neuropathy claim 1 , diabetic retinopathy claim 1 ...

2,3-DIHYDROFURO[2,3-c]PYRIDIN-2-YLPIPERIDINE DERIVATIVES

The present invention relates to compounds of general formula I, 2. The compound according to claim 1 , wherein{'sup': Q', 'Q, 'Lis selected from the group L-G2 consisting of H and methyl, a salt thereof.'}3. The compound according to claim 1 , wherein{'sup': 1', '1, 'sub': 3', '3, 'Ris selected from a group R-G2 consisting of —CH(CH)(CF), or a salt thereof.'}4. The compound according to selected from:(a) 4-[5-(4-Methanesulfonyl-phenyl)-2,3-dihydro-furo [2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester,(b) 4-[5-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester,(c) 4-[5-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester, and(d) 4-[5-(4-Methanesulfonyl-phenyl)-2-methyl-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester,or an enantionmer, diastereomer, or salt thereof.5. The compound according to selected from:(1) (S)-4-[(R)-5-(4-Methanesulfonyl-phenyl)-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester,(2) (R)-4-[(R)-5-(4-Methanesulfonyl-phenyl)-2,3-dihydro-furo [2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester,(3) (R)-4-[(R)-5-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester,(4) (S)-4-[(R)-5-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester,(5) (S)-4-[(R)-5-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester,(6) (R)-4-[(R)-5-(1-Methanesulfonyl-1,2,3,6-tetrahydro ...

TRIAZINONE AND DIAZINONE DERIVATIVES USEFUL AS HSP90 INHIBITORS

The present invention relates to compounds according to formulae (IA) to (ID) and compositions that inhibit the activity of Hsp90. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a compound of the invention, or a composition comprising such a compound. 2. The compound of claim 1 , wherein Rand Rare each independently —OH claim 1 , —SH claim 1 , or —NHR.3. The compound of claim 1 , wherein Ris a C1-C6 alkyl claim 1 , a C1-C6 haloalkyl claim 1 , a C1-C6 alkoxy claim 1 , a C1-C6 haloalkoxy claim 1 , a C1-C6 alkyl sulfanyl or a C3-C6 cycloalkyl.4. The compound of claim 1 , wherein Rand R claim 1 , for each occurrence claim 1 , are independently —H claim 1 , —C(O)R claim 1 , —C(O)NRR claim 1 , —C(O)OR claim 1 , an optionally substituted alkyl claim 1 , an optionally substituted alkenyl claim 1 , an optionally substituted alkynyl claim 1 , an optionally substituted cycloalkyl claim 1 , an optionally substituted cycloalkenyl claim 1 , an optionally substituted heterocyclyl claim 1 , an optionally substituted aryl claim 1 , an optionally substituted heteroaryl claim 1 , an optionally substituted aralkyl claim 1 , or an optionally substituted heteraralkyl.5. The compound of claim 4 , wherein Ris independently —H claim 4 , —C(O)R claim 4 , —C(O)NRR claim 4 , or —C(O)OR.6. The compound of claim 5 , wherein claim 5 , R claim 5 , is —H or lower alkyl.7. The compound of claim 1 , wherein{'sub': 2', '3, 'Rand Rare each independently —OH or —SH;'}{'sub': '4', 'Ris a C1-C6 alkyl or a C3-C6 cycloalkyl;'}{'sub': 14', '7', '10', '11', '7', '15, 'Ris independently —H, —C(O)R, —C(O)NRR, or —C(O)OR; and R, is —H or lower alkyl.'}8. The compound of claim 1 , wherein Rand Rtaken together form an optionally substituted heterocyclyl or an optionally substituted heteroaryl.10. The ...

Pyrido [2, 3 - b] pyrazine derivatives and their therapeutical uses

The present invention relates to novel pyrido[2,3-b]pyrazine derivatives of formula (I) and to the use of such compounds in which the inhibition, regulation and/or modulation of signal transduction by ATP consuming proteins like kinases plays a role, particularly to inhibitors of TGF-beta receptor kinases, and to the use of such compounds for the treatment of kinase-induced diseases, in particular for the treatment of tumors.

NOVEL FUSED RING COMPOUND AND ORGANIC LIGHT-EMITTING DEVICE INCLUDING THE SAME

A fused ring compound represented by Formula 1: 2. The fused ring compound of claim 1 , wherein Xis one of S claim 1 , O claim 1 , and Si(R)(R).3. The fused ring compound of claim 1 , wherein Yand Yare each N claim 1 , and Yis C; Yand Yare each N claim 1 , and Yis C; Yand Yare each N claim 1 , and Yis C; or Y claim 1 , Y claim 1 , and Yare each N.4. The fused ring compound of claim 1 , wherein Yand Yare each N claim 1 , and Yis C; or Y claim 1 , Y claim 1 , and Yare each N.6. The fused ring compound of claim 1 , wherein Arto Arare each independently one of a substituted or unsubstituted C-Caryl group claim 1 , and a substituted or unsubstituted C-Cheteroaryl group;{'sub': 1', '3, 'Lto Lare each independently one of a substituted or unsubstituted phenylene group, and a substituted or unsubstituted naphthalene group; and'}a, b and c are each independently an integer from 0 to 1.7. The fused ring compound of claim 1 , wherein Ato Arare each independently one of a substituted or unsubstituted phenyl group claim 1 , a substituted or unsubstituted naphthyl group claim 1 , a substituted or unsubstituted anthryl group claim 1 , a substituted or unsubstituted phenanthrenyl group claim 1 , a substituted or unsubstituted phenalenyl group claim 1 , a substituted or unsubstituted pyrenyl group claim 1 , a substituted or unsubstituted chrysenyl group claim 1 , a substituted or unsubstituted triphenylenyl group claim 1 , a substituted or unsubstituted tetracenyl group claim 1 , a substituted or unsubstituted tetraphenyl group claim 1 , a substituted or unsubstituted benzoanthryl group claim 1 , a substituted or unsubstituted benzophenanthrenyl group claim 1 , a substituted or unsubstituted biphenyl group claim 1 , a substituted or unsubstituted terphenyl group claim 1 , a substituted or unsubstituted indenyl group claim 1 , a substituted or unsubstituted fluorenyl group claim 1 , a substituted or unsubstituted benzofluorenyl group claim 1 , a substituted or unsubstituted ...

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 .

INDOLE DERIVATIVES USEFUL AS CCR2 ANTAGONISTS

Disclosed are the CCR2 antagonists of Formula I: I or pharmaceutically acceptable salt thereof wherein R7, A, X, B, and n are defined herein. Also disclosed are pharmaceutical compositions containing the compounds, methods of treatment using the compounds, and compositions to treat diseases or disorders associated with CCR2 activity. 10. A pharmaceutical composition comprising at least one compound of or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.11. A method for modulation of CCR2 receptor activity in a mammal which comprises the administration of an effective amount of the compound of .12. A method for the prevention or treatment of an inflammatory and immunoregulatory disorder or disease which comprises the administration to a patient of an effective amount of the compound of .13. A method for the prevention or treatment of rheumatoid arthritis which comprises the administration to a patient of an effective amount of the compound of .1417-. (canceled) The present invention relates to novel compounds useful as CCR2 antagonists or modulators, pharmaceutical compositions containing the compounds and methods of treatment using the compounds, and compositions to treat diseases or disorders associated with CCR2 activity.Inflammation is a complex response of vascularized tissues to harmful signals such as pathogens, injured cells or irritants. During inflammation leukocytes migrate into the inflamed tissue to start the healing process. This complex process is modulated by adhesion molecules and chemoattractants. Inflammation also plays a role in diseases such as hay fever, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and in atherosclerosis. As a result, there has been increased interest in the molecules involved in the inflammation response, including chemokines and their receptors, as potential drug targets for the management of such disorders.Chemokines are a group of cytokines made up of 70 ...

TRIAZOLOPYRIDINE COMPOUNDS AS PIM KINASE INHIBITORS

Compounds of Formula I: in which R, R, R, Rand Rhave the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by PIM-1 and/or PIM-2 and/or PIM-3 kinases. 3. A compound of claim 1 , wherein Ris selected from H claim 1 , (1-6C)alkyl claim 1 , (3-6C)cycloalkyl optionally substituted with —CHOH or —CHO(1-4C alkyl) claim 1 , (1-6C)alkoxy claim 1 , trifluoro(1-6C)alkoxy claim 1 , hydroxy(2-6C)alkoxy claim 1 , (1-3C alkoxy)(2-6C)alkoxy claim 1 , and (3-6C)cycloalkylmethoxy.4. A compound of claim 3 , wherein Ris selected from H claim 3 , methyl claim 3 , ethyl claim 3 , isopropyl claim 3 , tert-butyl claim 3 , cyclopropyl claim 3 , methoxy claim 3 , ethoxy claim 3 , isopropoxy claim 3 , trifluoromethoxy claim 3 , 2-hydroxyethoxy claim 3 , 2-hydroxypropoxy claim 3 , 3-hydroxypropoxy claim 3 , 2-methoxyethoxy claim 3 , 3-methoxypropoxy claim 3 , 2-methoxypropoxy claim 3 , 3-methoxyprop-2-oxy claim 3 , 2-ethoxyethoxy claim 3 , 1 claim 3 ,3-dimethoxypropan-2-yloxy and cyclopropylmethoxy.5. A compound of claim 4 , wherein Ris H.6. A compound of claim 3 , wherein R(1-3C alkoxy)(2-6C)alkoxy.7. (canceled)8. A compound according to claim 1 , wherein Ris selected from H claim 1 , (1-3C alkoxy)(1-6C)alkyl claim 1 , hydroxy(2-6C)alkoxy claim 1 , and (1-6C)alkoxy which is optionally substituted with (1-6C alkyl)C(═O)O— or amino(1-6C alkyl)C(═O)O—.9. A compound according to claim 8 , wherein Ris selected from H claim 8 , 2-methoxyethoxy claim 8 , 3-methoxyprop-2-oxy claim 8 , 2-methoxypropoxy claim 8 , 2-ethyoxyethoxy claim 8 , and 2-hydroxyethoxy.10. A compound according to claim 9 , wherein Ris H.11. A compound according to claim 1 , wherein Ris selected from halogen claim 1 , CN claim 1 , OH claim 1 , (1-6C)alkyl claim 1 , fluoro(1-6C)alkyl claim 1 , difluoro(1-6C)alkyl claim 1 , trifluoro(1-6C)alkyl claim 1 , hydroxy(1-6C)alkyl claim 1 , fluoro(1-6C)alkoxy claim 1 , difluoro(1-6C)alkoxy claim 1 , trifluoro(1-6C)alkoxy ...

Irak inhibitors and uses thereof

The present invention provides furano- and pyrrolo-pyrimidine and pyridine compounds, compositions thereof, and methods of using the same.

FUSED PYRIMIDINES AND SUBSTITUTED QUINAZOLINES AS INHIBITORS OF P97

A group of fused two ring pyrimidine compounds having a heterocycles substituent at the 2 position and a substituted amine at the 4 position as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the pyrimidine and other ring are disclosed. In addition a group of quinazoline compounds having similar substituents at the 2 and 4 positions as well as at other positions are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity. 2. A fused pyrimidine compound according to wherein the A ring is a benzo ring claim 1 , a cyclohexadieno ring claim 1 , a cyclohexeno ring claim 1 , a cyclopentadieno ring claim 1 , or a cyclopenteno ring.3. A fused pyrimidine ring according to wherein the A ring is a heterocyclyl or heteroaryl ring.4. A fused pyrimidine compound according to wherein the heterocyclyl or heteroaryl ring of ring A is a pyridino ring claim 3 , a pyrimidino ring claim 3 , a pyrazidino ring claim 3 , a thiapiperidino claim 3 , a morpholino claim 3 , a pyrrolo ring claim 3 , a thiopheno ring claim 3 , a furano ring claim 3 , an oxazolo ring claim 3 , a thiazolo ring or any saturated claim 3 , partially unsaturated or positional isomer thereof.6. A fused pyrimidine compound according to wherein the Het ring is an indolyl claim 5 , isoindolyl claim 5 , benzothiophenyl claim 5 , benzofuranyl claim 5 , benzoimidazolyl claim 5 , benzothiazolyl claim 5 , benzooxazolyl claim 5 , pyridinopyrrolyl claim 5 , pyridinothiophenyl claim 5 , pyridinofuranyl claim 5 , pyridinoimidazolyl claim 5 , pyridinothiazolyl claim 5 , pyridinooxazolyl claim 5 , pyrimidinopyrrolyl claim 5 , pyrimidinothiophenyl claim 5 , pyrimidinofuranyl claim 5 , pyrimidinoimidazolyl claim 5 , pyrimidineothiazolyl claim 5 , pyrimidinooxazolyl claim 5 , pyrazolinopyrrolyl claim 5 , pyrazolinothiophenyl claim 5 , pyrazolinofuranyl claim 5 , ...

COMPOSITIONS AND METHODS FOR INHIBITING CYTOCHROME P450

Methods of inhibiting cytochrome P450 enzymes are provided that can be used for improving the treatment of diseases by preventing degradation of drugs or other molecules by cytochrome P450. Pharmaceutical compositions are provided that can act as boosters to improve the pharmacokinetics, enhance the bioavailability, and enhance the therapeutic effect of drugs that undergo in vivo degradation by cytochrome P450 enzymes. 125-. (canceled)28. The compound according to wherein X is selected from the group consisting of alkyl claim 27 , alkenyl claim 27 , alkynyl claim 27 , alkoxyalkyl claim 27 , cycloalkyl claim 27 , cycloalkylalkyl claim 27 , heterocycloalkyl claim 27 , heteroaryl claim 27 , heterocycloalkylalkyl claim 27 , aryl claim 27 , aralkyl claim 27 , and heteroaralkyl; wherein X optionally is substituted with one or more substituents selected from the group consisting of C-Calkenyl claim 27 , C-Calkynyl claim 27 , C-Ccycloalkyl claim 27 , C-Ccycloalkenyl claim 27 , heterocyclo; halo claim 27 , OR claim 27 , ROH claim 27 , R-halo claim 27 , NO claim 27 , CN claim 27 , COR claim 27 , CON(R) claim 27 , C(S)R claim 27 , C(S)N(R) claim 27 , SON(R) claim 27 , SR claim 27 , SOR claim 27 , N(R) claim 27 , N(R)COR claim 27 , NRS(O)R claim 27 , NRC[═N(R)]N(R) claim 27 , N(R)N(R)COR claim 27 , NRPON(R) claim 27 , NRPOOR claim 27 , oxo claim 27 , ═N—OR claim 27 , ═N—N(R) claim 27 , ═NR claim 27 , ═NNRC(O)N(R) claim 27 , ═NNRCOR claim 27 , ═NNRS(O)N(R) claim 27 , and ═NNRS(O)(R).29. The compound according to or wherein X is selected from the group consisting of alkyl claim 27 , cycloalkyl claim 27 , aryl claim 27 , aralkyl claim 27 , heteroaryl claim 27 , and heteroaralkyl.30. The compound according to wherein X optionally is substituted with one or more substituents selected from the group consisting of halo claim 27 , OR claim 27 , ROH claim 27 , R-halo claim 27 , CN claim 27 , COR claim 27 , CON(R) claim 27 , SON(R) claim 27 , SR claim 27 , SOR claim 27 , N(R) claim 27 , ...

COMPOUNDS AND COMPOSITIONS AS C-KIT KINASE INHIBITORS

The invention provides compounds and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of c-kit or c-kit and PDGFR (PDGFRα, PDGFRβ) kinases. 3. The method of claim 1 , wherein Ris selected from —CHand F.4. The method of claim 3 , wherein Ris —CH.5. The method of claim 1 , wherein each Ris independently selected from H claim 1 , F and —CH.6. The method of claim 5 , wherein each Ris H.7. The method of claim 1 , wherein Ris selected from an unsubstituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N and O claim 1 , a piperidinone claim 1 , a oxazolidin-2-one claim 1 , pyrrolidinone claim 1 , a pyrrolidin-2-one and a substituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N and O claim 1 ,{'sup': 3', '4', '4', '4', '7', '5', '9', '4', '9', '4', '4', '4', '4', '9', '4', '8', '9', '8', '4', '7', '8', '4', '4', '9', '4', '9', '4, 'sub': 1', '6', '1', '6', '2', 'n', '2', 'n', 'NR42', '2', 'n', '2', 'n', '2', '2', '2', '2', '2', '2', '2', '2', 'n', '2', '2', 'n', '1, 'wherein the substituted 4-6 membered heterocycloalkyl of Ris substituted with 1-4 substituents independently selected from C-Calkyl, halo, —CN, C-Chaloalkyl, —OR, —C(═O)OR, —C(═O)R, —C(═O)R, —C(═O)OR, —(CR)OR, —C(═O)O(CR)OR, —C(═O), —NRC(═O)OR, —NRC(═O)(CR)OR, —R, —(CR)R, —S(═O)R, —S(═O)R, —S(═O)R, —S(═O)N(R), —S(═O)NHC(═O)OR, —S(═O)(CR)OR, —S(═O)(CR)C(═O)ORand a Calkyl bridge.'}8. The method of claim 7 , wherein each Ris independently selected from H claim 7 , methyl claim 7 , ethyl claim 7 , propyl claim 7 , butyl claim 7 , i-propyl and t-butyl.9. The method of claim 7 , wherein each Ris cyclopropyl ...

FURO[3, 2-B] PYRR0L-3-ONES AS CATHESPIN S INHIBITORS

A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, 3. The method according to claim 1 , wherein the cysteine proteinase is a CAC1 cysteine proteinase.4. The method according to claim 3 , wherein the CAC1 cysteine proteinase is cathepsin S. This application is a Divisional patent application of U.S. Ser. No. 13/745,413, filed Jan. 13, 2013, which is a Divisional patent application of U.S. Ser. No. 12/853,005, filed Aug. 9, 2010, now U.S. Pat. No. 8,389,737 issued Mar. 5, 2013, which is a Continuation patent application that claims priority to PCT patent application number PCT/GB2009/000653, filed Mar. 11, 2009, which claims the priority to Great Britain patent application number 0804701.1, filed on Mar. 13, 2008, the entirety of which are herein incorporated by reference.The present invention relates to compounds that are inhibitors of cysteine proteinases, pharmaceutical compositions containing said compounds, and their use in therapy. More specifically, the invention relates to compounds that are inhibitors of cathepsin S, a cysteine proteinase of the CA clan. Such compounds are particularly useful for the in vivo therapeutic treatment of diseases in which participation of cathepsin S is implicated.Proteinases form a substantial group of biological molecules which to date constitute approximately 2% of all the gene products identified following analysis of several completed genome sequencing programmes. Proteinases have evolved to participate in an enormous range of biological processes, mediating their effect by cleavage of peptide amide bonds within the myriad of proteins found in nature. This hydrolytic action is performed by initially recognising, then binding to, particular three-dimensional electronic surfaces displayed by a protein, which align the bond for cleavage precisely within the proteinase catalytic site. Catalytic hydrolysis then commences through ...

Novel Bicyclic Pyridinones

Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I 2. The compound according to wherein X is imidazolyl claim 1 , pyrazolyl claim 1 , isothiazolyl claim 1 , thiazolyl claim 1 , isoxazolyl claim 1 , oxazolyl or pyridyl.3. The compound according to wherein X is imidazolyl.4. The compound according to wherein Ris Calkyl.5. The compound according to wherein Ris methyl optionally substituted with one hydroxyl or Calkoxy or one to three fluoro; y is two or three and z is 1.6. The compound according to wherein Ris independently hydrogen claim 5 , halogen claim 5 , cyano claim 5 , —CF claim 5 , Calkyl claim 5 , (C)bicycloalkyl claim 5 , —(C(R))—(Ccycloalkyl) claim 5 , —(C(R))-(4- to 10-membered heterocycloalkyl) claim 5 , —(C(R))—(Caryl) claim 5 , —(C(R))-(5- to 10-membered heteroaryl) claim 5 , —(C(R))—ORor —C(O)R; wherein the alkyl claim 5 , cycloalkyl claim 5 , bicycloalkyl claim 5 , heterocycloalkyl claim 5 , aryl claim 5 , or heteroaryl moieties may be independently substituted with one to three R.7. The compound according to wherein Ris independently hydrogen claim 6 , Calkyl claim 6 , fluoro claim 6 , —CF claim 6 , —CHFor —OR; and Ris hydrogen claim 6 , Calkyl claim 6 , —CFor Caryl.8. The compound according to wherein Ris phenyl claim 7 , naphthalene claim 7 , 2 claim 7 ,3-dihydro-1H-indene claim 7 , quinoline claim 7 , isoquinoline claim 7 , pyrazole claim 7 , benzo[b]furan claim 7 , 2 claim 7 ,3-dihydrobenzofuran claim 7 , 1 claim 7 ,2-benzisothiazole claim 7 , 1 claim 7 ,3-benzothiazole claim 7 , benzofuro[3 claim 7 ,2-c]pyridine claim 7 , pyridine claim 7 , carbazole claim 7 , benzo[d]isoxazole claim 7 , benzocyclobutane claim 7 , 1 claim 7 ,2 claim 7 ,3 claim 7 ,4-tetrahydronaphthalene claim 7 , dibenzo[b claim 7 ,d]thiophene claim 7 , dibenzo[b claim 7 ,d]furan or cinnoline.9. The compound according to wherein Ris hydrogen claim 8 , chloro claim 8 , fluoro claim 8 , bromo claim 8 ...

Protein kinase d inhibitors

Compounds according to Formula (I), are potent inhibitors of protein kinase D (pan-PKD) activity. PKD controls key signaling cascades in cells, affecting cell proliferation, gene transcription, and protein trafficking. Accordingly, pharmaceutically acceptable compositions of the inventive compounds are candidate therapeutics for pathological conditions conditioned by changes in PKD activity.

2-AMINO-4-ARYLTHIAZOLE COMPOUNDS AS TRPA1 ANTAGONISTS

The present invention is related to 2-amino-4-arylthiazole derivatives as TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPA1 (Transient Receptor Potential subfamily A, member 1). Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPA1. 142.-. (canceled)43. A compound selected from[2-{[(1,3-Dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)acetyl]imino}-4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-3 (2H)-yl]methyl-2-methyl propanoate;[4-[2,4-Difluoro-3-(trifluoromethyl)phenyl]-2-{[(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)acetyl]imino}-1,3-thiazol-3(2H)-yl]methyl-2-methylpropanoate;[4-[3-Chloro-4-(trifluoromethoxy)phenyl]-2-{[(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydrofuro[2,3-d]pyrimidin-5-yl)acetyl]imino}-1,3-thiazol-3(2H)-yl]methyl 2,2-dimethylpropanoate;[4-[2,4-Difluoro-3-(trifluoromethyl)phenyl]-2-{[(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)acetyl]imino}-1,3-thiazol-3(2H)-yl]methyl L-prolinate;[4-[2,4-Difluoro-3-(trifluoromethyl)phenyl]-2-{[(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)acetyl]imino}-1,3-thiazol-3(2H)-yl]methyl L-prolinate hydrochloride;[2-{[(1,3-Dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)acetyl]imino}-4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-3 (2H)-yl]methylpiperidine-4-carboxylate;[2-{[(1,3-Dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)acetyl]imino}-4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-3 (2H)-yl]methylpiperidine-4-carboxylate hydrochloride;[4-[2,4-Difluoro-3-(trifluoromethyl)phenyl]-2-{[(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d] ...

DNA-PK INHIBITORS

The present invention relates to compounds useful as inhibitors of DNA-PK. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. 1. A compound selected from the list of compounds in Table 3.2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.3. A method of sensitizing a cell to an agent that induces a DNA lesion comprising the step of contacting the cell with a compound according to claim 1 , or a pharmaceutical composition comprising said compound.4. A method of potentiating a therapeutic regimen for the treatment of cancer in a patient comprising the step of administering to said patient an effective amount of a compound according to claim 1 , or a pharmaceutical composition comprising said compound. The present invention relates to compounds useful as inhibitors of DNA-dependent protein kinase (DNA-PK). The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of cancer.Ionizing radiation (IR) induces a variety of DNA damage of which double strand breaks (DSBs) are the most cytotoxic. These DSBs can lead to cell death via apoptosis and/or mitotic catastrophe if not rapidly and completely repaired. In addition to IR, certain chemotherapeutic agents including topoisomerase II inhibitors, bleomycin, and doxorubicin also cause DSBs. These DNA lesions trigger a complex set of signals through the DNA damage response network that function to repair the damaged DNA and maintain cell viability and genomic stability. In mammalian cells, the predominant repair pathway for DSBs is the Non-Homologous End Joining Pathway (NHEJ). This pathway functions regardless of the phase of the cell cycle and does not require a template to re-ligate the broken DNA ends. NHEJ requires coordination ...

Phosphorescent emitters with phenylimidazole ligands

Phosphorescent materials are provided, where the materials comprise a coordination compound having at least one ligand L 3 having Formula (I): wherein A and B are each independently a 5-membered or 6-membered carbocyclic or heterocyclic ring; wherein R A , R B , R C , and R D each represent mono, di, tri, tetra substitutions, or no substitution; wherein Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , Z 7 , and Z 8 are each selected from N or C; wherein at least one of Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , Z 7 , and Z 8 is N; wherein one of Z 1 , Z 2 , Z 3 , and Z 4 is C that is bonded to N of A; wherein Z is selected from the group consisting of BR, NR, PR, O, S, Se, C═O, S═O, SO 2 , CRR′, SiRR′, and GeRR′; wherein R, R′, R A , R B , R C , and R D are described herein; wherein L 3 is coordinated to a metal M 1 ; and wherein L 3 may be linked with other ligands to comprise a tridentate, tetradentate, pentadentate, or hexadentate ligand. Devices, such as organic light emitting devices, comprising such compounds are also provided.

AURORA KINASE MODULATORS AND METHOD OF USE

The present invention relates to chemical compounds having a general formula I 4. The compound of claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', '10', '10, 'sub': 2', '2', '1-10', '1-10, 'Cis CRand Ris H, halo, haloalkyl, haloalkoxyl, CN, OH, SH, NO, NH, acetyl, C-alkyl or C-alkoxyl;'}{'sup': '2', 'Cis N; and'}{'sup': '2', 'sub': 2', '1-10', '1-10, 'Ris H, halo, NO, CN, Calkyl or Calkoxyl.'}5. The compound of claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', '15', '15, 'sub': '2', 'Lis NR, O, CHR, S, C(O), S(O) or SO; and'}{'sup': '2', 'sub': 2', '1-10', '1-10, 'Ris H, halo, NO, CN, Calkyl or Calkoxyl.'}6. The compound of claim 5 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 5 , wherein{'sup': 2', '15, 'Lis NR, O or S;'}{'sup': 3', '4', '9, 'each of R, Rand R, independently, is H;'}{'sup': 1', '10, 'Cis CR; and'}{'sup': 1', '2', '15, 'Z is phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, thiophenyl, furyl, pyrrolyl, pyrazolyl, thieno-pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, oxazolyl, oxadiazolyl, isoxazolyl or isothiazolyl, wherein Land L, together, are para-oriented to one another on ring Z, wherein ring Z is optionally substituted with 1-5 substitutions of R.'}7. The compound of claim 6 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 6 , wherein Rand Rtaken together with the carbon atoms to which they are attached form a fully saturated or partially or fully unsaturated 5- or 6-membered ring of carbon atoms optionally including 1-3 heteroatoms selected from O claim 6 , N claim 6 , or S claim 6 , and the ring optionally substituted independently with 1-4 substituents of R claim 6 , Ror R.8. The compound of claim 6 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 6 , wherein{'sup': 1', '2, 'each of Aand A, independently, is N; and'}{'sup': 6', '15, ' ...

FUSED HETEROCYCLIC DERIVATIVES AS S1P MODULATORS

The present invention relates to a fused heterocyclic derivative of the formula (I) The variables R1-R4, z, A, Q, X and Y are as defined in the claims. The following heterocycles are exemplified sub-structures of formula (I): The compounds of formula (I) are modulators of the S1P receptor (Sphingosine-1-phosphate receptor), More specifically, they are agonists of S1P5. The compounds have therapeutic use in treatment of cognitive disorders, age-relate cognitive decline and dementia. 2. The compound of claim 1 , wherein 'a group selected from a (3-6C)cycloalkyl group and a (8-10C)bicyclic group wherein the group is optionally substituted with a halogen atom, (1-4C)alkyl, and a phenyl group wherein the phenyl group is optionally substituted with at least one substituent independently selected from a halogen atom, cyano, (1-4C)alkyl, (1-4C)alkoxy, a trifluoromethyl, and a trifluoromethoxy;', 'R1 is selected from'}{'sub': '2', 'W is selected from a bond, —O—, —CO—, —S—, —SO—, —SO—, —NH—, —CH═CH—, —C≡C—, and a trans-cyclopropylene; and'}n is an integer from 0 to 4; andR2 is selected from H and at least one substituent independently selected from a halogen atom, (1-4C)alkyl optionally substituted with at least one fluoro, and (1-4C)alkoxy optionally substituted with at least one fluoro atom.5. The compound of claim 1 , wherein Y is O.6. The compound of claim 1 , wherein R4 is selected from —(CH)—COOH claim 1 , —(CH)—COOH claim 1 , —CH—CHCH—COOH claim 1 , —CH—C(CH)—COOH claim 1 , —CHCH—CH—COOH claim 1 , —CH—CF—COOH claim 1 , and 1 claim 1 ,3-cyclobutylene-COOH.7. The compound of claim 1 , wherein R1 is a phenyl group optionally substituted with at least one substituent independently selected from halogen claim 1 , cyano claim 1 , (1-4C)alkyl optionally substituted with at least one halogen atom claim 1 , (1-4C)alkoxy optionally substituted with at least one halogen atom claim 1 , amino claim 1 , dimethylamino claim 1 , and (3-6C)cycloalkyl optionally substituted with a ...

NOVEL TETRACYCLIC HETEROATOM CONTAINING DERIVATIVES USEFUL AS SEX STEROID HORMONE RECEPTOR MODULATORS

The present invention is directed to novel tetracyclic heteroatom containing derivatives, pharmaceutical compositions containing them, their use in the treatment of disorders mediated by one or more sex steroid hormone receptors and processes for their preparation. 18.-. (canceled)1012.-. (canceled)13. The method of claim 9 , wherein the disorder mediated one or more sex steroid hormone receptors in selected from the group consisting of hot flashes claim 9 , vaginal dryness claim 9 , osteopenia claim 9 , osteoporosis claim 9 , hyperlipidemia claim 9 , loss of cognitive function claim 9 , degenerative brain diseases claim 9 , cardiovascular diseases claim 9 , cerebrovascular diseases claim 9 , hormone sensitive cancers claim 9 , hormone sensitive hyperplasia claim 9 , endometriosis claim 9 , uterine fibroids claim 9 , osteoarthritis claim 9 , prostate carcinoma claim 9 , benign prostatic hyperplasia (BPH) claim 9 , hirsitutism claim 9 , alopecia claim 9 , anorexia nervosa claim 9 , breast cancer claim 9 , acne claim 9 , AIDS claim 9 , cachexia claim 9 , endometriosis claim 9 , myoma claim 9 , dysfunctional bleeding claim 9 , tumors containing steroid receptors claim 9 , for male contraception claim 9 , for female contraception claim 9 , for male performance enhancement claim 9 , and for hormone replacement.1415.-. (canceled) This application claims the benefit of U.S. Provisional Application 60/611,376, filed on Sep. 20, 2004, which is incorporated by reference herein in its entirety.The present invention is directed to novel tetracyclic heteroatom containing derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders mediated by one or more sex steroid hormone receptors. The compounds of the present invention are selective estrogen, selective androgen and/or progestin receptor modulators.Estrogens are a group of female hormones essential for the reproductive process and for the development of the uterus, breasts, and other ...

NOVEL 6-ARYLAMINO PYRIDONE CARBOXAMIDE AS MEK INHIBITORS

The invention provides novel substituted 6-arylamino pyridone carboxamides represented by Formula I, or a pharmaceutically acceptable salt, solvate, poly-morph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of MEK and are useful in the treatment of inflammatory diseases, cancer and other hyperproliferative diseases. The invention further provides a method of treatment for inflammatory diseases, cancer and other hyperproliferative diseases in mammals, especially humans. 2. The compound according to claim 1 , wherein one of X and W is O or S claim 1 , and the other is C claim 1 , and Y is C; or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , poly-morph claim 1 , ester claim 1 , tautomer or prodrug thereof.4. The compound according to claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , C-Calkyl optionally substituted with one or more substituents selected from the group consisting of halogen claim 1 , hydroxyl and alkoxy; C-Calkoxyl optionally substituted with one or more substituents selected from the group consisting of halogen claim 1 , hydroxyl and cycloalkyl; C-Calkenyl; C-Ccycloalkyl optionally substituted with C-Calkyl or C-Calkenyl; 5 or 6 membered monocyclic or 9 to 13 membered bicyclic heteroaryl with O claim 1 , N claim 1 , or S as the hetero atom; 5 or 6 membered monocyclic or 9 to 13 membered bicyclic aryl optionally substituted with one or more substituents selected from the group consisting of halogen claim 1 , cyano claim 1 , C-Calkoxy and hydroxyl; arylcycloalkyl in which aryl is monocyclic or bicyclic aryl and cycloalkyl has 1 to 6 carbon atoms; and C-Calkyl C-Ccycloalkyl; or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , polymorph claim 1 , ester claim 1 , tautomer or prodrug thereof.5. The compound according to claim 4 , wherein Ris selected from the group consisting of C-Calkyl and C-Calkoxy claim 4 , where ...

Partially Saturated Tricyclic Compounds and Methods of Making and Using Same

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2. 2. The tricyclic compound of claim 1 , wherein X′ is selected from the group consisting of: —O—* claim 1 , —N(R)—* claim 1 , —C(RR)—C(RR)—* claim 1 , —C(R)═C(R)—* claim 1 , —O—C(RR)—* claim 1 , —N(R)—C(RR)—* claim 1 , —O—C(O)—* claim 1 , —N(R)—C(O)—* claim 1 , —N═C(R)—* and —O—C(RR)—C(RR)—*;{'sup': '+', 'wherein the and * indicate the attachment points of X′ as indicated in Formula I.'}3. The tricyclic compound of claim 1 , wherein Xis selected from the group consisting of: —NH—* claim 1 , —O—CH—* claim 1 , —NH—CH—* claim 1 , —N═CH—* and —CH═CH—*;{'sup': '+', 'wherein the and * indicate the attachment points of X′ as indicated in Formula I.'}4. The tricyclic compound of claim 1 , wherein Xis selected from the group consisting of: —O—* claim 1 , —N(R)—* claim 1 , —C(RR)—C(RR)—* claim 1 , —O—C(RR)—* claim 1 , —N(R)—C(RR)—* claim 1 , —O—C(O)—* claim 1 , —N(R)—C(O)—* claim 1 , and —O—C(RR)—C(RR)—*; wherein the and * indicate the attachment points of Xas indicated in Formula II.5. The tricyclic compound of claim 1 , wherein Xis selected from the group consisting of: —O—CH—* and —NH—CH—*; wherein the and * indicate the attachment points of Xas indicated in Formula II.6. The tricyclic compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , Rand Rare independently selected for each occurrence from the group consisting of hydrogen and methyl.7. The tricyclic compound of claim 5 , wherein R claim 5 , R claim 5 , R claim 5 , Rand Rare hydrogen.8. The tricyclic compound of claim 1 , wherein R claim 1 , R claim 1 , Rand Rare independently selected for each occurrence from the group consisting of hydrogen claim 1 , fluorine claim 1 , cyano and Calkyl.9. The tricyclic compound of claim 7 , ...

INHIBITORS OF THE PLASMODIAL SURFACE ANION CHANNEL AS ANTIMALARIALS

Disclosed are inhibitors of the plasmodial surface anion channel (PSAC) inhibitors and the use thereof in treating or preventing malaria in an animal such as a human, comprising administering an effective amount of an inhibitor or a combination of inhibitors. An example of such an inhibitor is a compound of formula I, 232-. (canceled)33. The method of claim 1 , comprising administering a compound of formula (V) claim 1 , wherein Ris alkyl or alkoxy and Rand Rare hydrogen.34. The method of claim 33 , wherein Ris methyl or methoxy.35. The method of claim 33 , wherein Ris alkyl and Ris alkyl claim 33 , cycloalkyl claim 33 , or aryl claim 33 , wherein said aryl is optionally substituted with one or more substituents selected from the group consisting of alkyl claim 33 , alkoxy claim 33 , halo claim 33 , hydroxy claim 33 , nitro claim 33 , cyano claim 33 , amino claim 33 , alkylamino claim 33 , aminoalkyl claim 33 , alkylcarbonyl claim 33 , alkoxycarbonyl claim 33 , aminocarbonyl claim 33 , and formyl.36. The method of claim 35 , wherein Ris alkyl claim 35 , cycloalkyl claim 35 , or aryl claim 35 , wherein said aryl is optionally substituted with one or more alkyl and/or alkoxy substituents.38. The method of claim 33 , wherein Ris hydrogen and Ris cycloalkyl or aryl claim 33 , which is optionally substituted with one or more alkyl and/or alkoxy substituents.40. The method of claim 1 , wherein an effective amount of a combination of compounds of formulas I and IV claim 1 , or pharmaceutically acceptable salts thereof claim 1 , is administered.41. The method of claim 1 , wherein an effective amount of a combination of compounds of formulas I and V claim 1 , or pharmaceutically acceptable salts thereof claim 1 , is administered.42. The method of claim 1 , wherein an effective amount of a combination of compounds of formulas IV and V claim 1 , or pharmaceutically acceptable salts thereof claim 1 , is administered.43. The method of claim 1 , wherein an effective amount of a ...

CYCLOPAMINE ANALOGS

The invention provides derivatives of cyclopamine having the following formula: 125.-. (canceled)27. A pharmaceutical composition comprising a compound of claim 26 , a pharmaceutically acceptable salt thereof claim 26 , or a mixture thereof claim 26 , and a pharmaceutically acceptable excipient.29. The compound of claim 28 , wherein said compound is epimerically pure.30. A pharmaceutical composition comprising a compound of claim 28 , a pharmaceutically acceptable salt thereof claim 28 , or a mixture thereof claim 28 , and a pharmaceutically acceptable excipient. This application is a continuation of U.S. application Ser. No. 15/289,887, filed Oct. 10, 2016, now allowed, which is a continuation of U.S. application Ser. No. 14/203,297, filed Mar. 10, 2014, now U.S. Pat. No. 9,492,435, which is a continuation of U.S. application Ser. No. 12/199,722, filed Aug. 27, 2008, now U.S. Pat. No. 8,669,365 which is a continuation of U.S. application Ser. No. 11/965,688, filed Dec. 27, 2007, now U.S. Pat. No. 7,812,164, which claims benefit under 35 U.S.C. § 119(e) to U.S. Application No. 60/941,596, filed Jun. 1, 2007 and U.S. Application No. 60/878,018, filed Dec. 28, 2006. The contents of these applications are hereby incorporated by reference in their entirety.The present invention generally relates to cyclopamine analogs and pharmaceutical compositions thereof, and methods for preparing such analogs and compositions. These compounds and compositions are useful for the treatment of disorders mediated by the hedgehog pathway, such as cancer.Inhibition of the hedgehog pathway in certain cancers has been shown to result in inhibition of tumor growth. For example, anti-hedgehog antibodies have been shown to antagonize the function of the hedgehog pathway and inhibit the growth of tumors. Small molecule inhibition of hedgehog pathway activity has also been shown to result in cell death in a number of cancer types.Research in this area has focused primarily on the elucidation of ...

Mth1 inhibitors for treatment of inflammatory and autoimmune conditions

A compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of autoimmune diseases and inflammatory conditions.

HETEROCYCLIC COMPOUND

The present invention provides a heterocyclic compound having a RORγt inhibitory action. 4. The compound or salt of claim 1 , wherein Ris a group represented by the formula: —C(R)(CH)(CH) wherein Ris bonded to one substituent on Ring A to form an optionally substituted 5-membered hydrocarbon ring claim 1 , wherein the one substituent on Ring A is bonded to the position adjacent to the bonding position of Ron Ring A.5. The compound or salt of claim 1 , wherein Ris cyclopropyl or cyclobutyl claim 1 , each optionally substituted.6. The compound or salt of claim 1 , wherein{'sup': 1', '1a', '1a', '1, 'sub': 3', '3, 'Ris a group represented by the formula: —C(R)(CH)(CH) wherein Ris bonded to one substituent on Ring A to form an optionally substituted 5-membered hydrocarbon ring, wherein the one substituent on Ring A is bonded to the position adjacent to the bonding position of Ron Ring A;'}{'sup': '4', 'Ris cyclopropyl or cyclobutyl, each optionally substituted; and'}Ring D is not formed.7. ((1R claim 1 ,2S)-2-(((5R)-5-((7-Fluoro-1 claim 1 ,1-dimethyl-2 claim 1 ,3-dihydro-1H-inden-5-yl)carbamoyl)-2-methoxy-7 claim 1 ,8-dihydro-1 claim 1 ,6-naphthyridin-6(5H)-yl)carbonyl)cyclopropyl)acetic acid or a salt thereof.8. cis-3-(((5R)-5-((7-Fluoro-1 claim 1 , l-dimethyl-2 claim 1 ,3-dihydro-1H-inden-5-yl)carbamoyl)-2-methoxy-7 claim 1 ,8-dihydro-1 claim 1 ,6-naphthyridin-6(5H)-yl)carbonyl)cyclobutanecarboxylic acid or a salt thereof.9. (cis-3-(((5R)-5-((7-Fluoro-1 claim 1 ,1-dimethyl-2 claim 1 ,3-dihydro-1H-inden-5-yl)carbamoyl)-2-methoxy-7 claim 1 ,8-dihydro-1 claim 1 ,6-naphthyridin-6(5H)-yl)carbonyl)cyclobutyl)acetic acid or a salt thereof.10. (cis-3-(((1R)-1-((7-Fluoro-1 claim 1 ,1-dimethyl-2 claim 1 ,3-dihydro-1H-inden-5-yl)carbamoyl)-6-(methoxymethyl)-3 claim 1 ,4-dihydroisoquinolin-2(1H)-yl)carbonyl)cyclobutyl)acetic acid or a salt thereof.11. A medicament comprising the compound or salt of .12. The medicament of claim 11 , which is a RORγt inhibitor.13. The medicament of ...

PIPERIDINE-DIONE DERIVATIVES

The invention provides novel compounds having the general formula: 5. The compound of claim 1 , wherein Ais NH.6. The compound of claim 1 , wherein Ais CR claim 1 , wherein Ris selected from the group consisting of H claim 1 , halo claim 1 , hydroxy claim 1 , C-C-hydroxyalkyl claim 1 , and NH.7. The compound of claim 1 , wherein Rand Rare H.8. The compound of claim 1 , wherein Ris Cl.9. The compound of claim 1 , wherein Ris NH-phenyl or NH-pyridinyl claim 1 , which phenyl or pyridinyl is substituted by halo.10. The compound of claim 1 , wherein R claim 1 , R claim 1 , Rand Rare H.11. The compound of claim 1 , wherein it is selected from the group consisting of the following compounds as racemates claim 1 , single stereoisomers claim 1 , tautomers and pharmaceutically acceptable salts thereof:1-[4-[5-(2-chlorophenyl)sulfanyl-4,6-dioxo-2-(3-thienyl)-2-piperidyl]phenyl]piperidine-4-carbonitrile;2-[[6-(6-bromo-2-pyridyl)-2,4-dioxo-6-(3-thienyl)-3-piperidyl]sulfanyl]benzonitrile;3-(2-chloro-5-hydroxy-phenyl)sulfanyl-6-[4-(1-piperidyl)phenyl]-6-(3-thienyl)piperidine-2,4-dione;3-(2-chlorophenoxy)-6-(4-morpholinophenyl)-6-(3-thienyl)piperidine-2,4-dione;3-(2-chlorophenoxy)-6-[4-(1-piperidyl)phenyl]-6-(3-thienyl)piperidine-2,4-dione;3-(2-chlorophenoxy)-6-[6-(2-cyclopropylethoxy)-2-pyridyl]-6-(3-thienyl)piperidine-2,4-dione;3-(2-chlorophenoxy)-6-[6-(3,4-difluorophenoxy)-2-pyridyl]-6-(3-thienyl)piperidine-2,4-dione;3-(2-chlorophenoxy)-6-[6-(4-fluoroanilino)-2-pyridyl]-6-(3-thienyl)piperidine-2,4-dione;3-(2-chlorophenoxy)-6-[6-(4-fluorophenoxy)-2-pyridyl]-6-(3-thienyl)piperidine-2,4-dione;3-(2-chlorophenyl)sulfanyl-1-methyl-6-(3-tetrahydropyran-4-yloxyphenyl)-6-(3-thienyl)piperidine-2,4-dione;3-(2-chlorophenyl)sulfanyl-1-methyl-6-[3-(tetrahydropyran-4-ylamino)phenyl]-6-(3-thienyl)piperidine-2,4-dione;3-(2-chlorophenyl)sulfanyl-6-(1H-indol-4-yl)-6-(3-thienyl)piperidine-2,4-dione;3-(2-chlorophenyl)sulfanyl-6-(2-fluorophenyl)-1-methyl-6-(3-thienyl)piperidine-2,4-dione;3-(2- ...

FUSED HETEROCYCLIC COMPOUND AND PEST CONTROL APPLICATIONS THEREOF

A fused heterocyclic compound represented by formula (1) or an N-oxide thereof has an excellent control effect on pests: 2. The fused heterocyclic compound according to claim 1 , wherein{'sup': '1', 'Ris a C1 to C6 alkyl group optionally having one or more halogen atoms or one or more cyclopropyl groups (wherein the cyclopropyl group optionally has one or more halogen atoms or one or more C1 to C3 alkyl groups), a C2 to C6 alkenyl group optionally having one or more halogen atoms, a C2 to C6 alkynyl group optionally having one or more halogen atoms or a C3 to C6 cycloalkyl group optionally having one or more halogen atoms or one or more C1 to C3 alkyl groups;'}{'sup': 2', '4', '5, 'R, Rand Rare the same or different and are a C1 to C3 alkyl group optionally having one or more halogen atoms, a halogen atom or a hydrogen atom;'}{'sup': 3', '7', '7', '7', '7', '7', '8, 'sub': m', '2, 'Ris a C1 to C6 alkyl group optionally having one or more halogen atoms, a 5- or 6-membered heterocyclic group optionally having one or more atoms or groups selected from group δ, OR, S(O)R, C(O)R, COR, C(O)NRR, a cyano group, a halogen atom or a hydrogen atom;'}{'sup': '6', 'Ris C1 to C6 alkyl group optionally having one or more halogen atoms, a C2 to C6 alkenyl group optionally having one or more halogen atoms, a C2 to C6 alkynyl group optionally having one or more halogen atoms, a C1 to C3 alkyl group having a thiazolyl group optionally having one or more atoms or groups selected from group δ, a C1 to C3 alkyl group having a pyridyl group optionally having one or more atoms or groups selected from group S or a hydrogen atom; and'}{'sup': 7', '8, 'Rand Rare the same or different and are a C1 to C6 alkyl group optionally having one or more halogen atoms or a hydrogen atom.'}3. The fused heterocyclic compound according to claim 1 , wherein the ring J is a benzene ring claim 1 , wherein the benzene ring optionally has one or more atoms or groups selected from group δ.4. The fused ...

AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES

Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds. 2. The compound of , wherein R is an 8- or 9-membered heteroaryl , unsubstituted or substituted as described for .4. The compound of , wherein , R is a five- or six-membered nitrogen-linked heterocycloalkyl ring fused to an unsubstituted or substituted phenyl or monocyclic heteroaryl , as defined in .6. The compound of claim 1 , wherein Ris H claim 1 , —C(O)R claim 1 , —COR claim 1 , —S(O)R claim 1 , or —SOR.7. (canceled)8. (canceled)9. The compound of claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , tert-butyl claim 1 , isobutyl claim 1 , isopentyl claim 1 , phenyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , thiophenyl claim 1 , imidazolyl claim 1 , pyrazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , thiazolyl claim 1 , triazoyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , pyridazinyl claim 1 , isoindolinyl claim 1 , azetidinyl claim 1 , oxetanyl claim 1 , pyrrolidinyl claim 1 , piperidinyl claim 1 , morpholinyl claim 1 , piperazinyl claim 1 , tetrahydrofuranyl claim 1 , tetrahydropyranyl claim 1 , or tetrahydrothiophenyl claim 1 , each unsubstituted or substituted.10. The compound of claim 1 , wherein Ris phenyl claim 1 , cycloalkyl claim 1 , heteroaryl claim 1 , or heterocycloalkyl claim 1 , each unsubstituted or substituted with one or more substituents selected from the group consisting of fluoro claim 1 , oxo claim 1 , methyl claim 1 , —CONH claim 1 , acetyl claim 1 , —SOmethyl claim 1 , —C(O)-isopropyl claim 1 , pyridazinyl claim 1 , triazolyl claim 1 , dimethylaminomethyl claim 1 , cyano claim 1 , methyl-triazolyl-methoxy claim 1 , trifluoromethoxy claim 1 , pyrrolidinylmethyl claim 1 , acetylamino claim 1 , tetrazolylmethyl claim 1 ...

THIENO[3,2-D]PYRIMIDINE-6-CARBOXAMIDES AND ANALOGUES AS SIRTUIN MODULATORS

Provided herein are novel substituted thieno[3,2-d]pyrimidine-6-carboxamide sirtuin inhibitors and methods of use thereof. The sirtuin inhibitors may be used for inhibiting a sirtuin-mediated biological process, and, e.g. for treating and/or preventing diseases and disorders including, but not limited to cancer, neurodegenerative disease and inflammation. Also provided herein are pharmaceutical compositions comprising these sirtuin inhibitors and compositions comprising a sirtuin inhibitor in combination with another therapeutic agent. 4. The compound or salt of claim 1 , wherein W is S.5. The compound or salt of claim 1 , wherein X is —C(═O)—NH.6. The compound or salt of claim 1 , wherein Y is selected from CH—(C-Cstraight chain or branched alkyl)-NH—C(═O)—R claim 1 , CH—(C-Cstraight chain or branched alkyl)-NRR claim 1 , N—(C-Cstraight chain or branched alkyl)-NH—C(═O)—R claim 1 , N—(C-Cstraight chain or branched alkyl)-NRR claim 1 , CH—(C-Cstraight chain or branched alkyl)-R claim 1 , and CH—(C-Cstraight chain or branched alkyl)-NH—C(═S)—R.15. The compound or salt of claim 1 , wherein Ris selected from a 5- to 6-membered saturated or unsaturated carbocycle or heterocycle claim 1 , —C-Cstraight chain or branched alkyl claim 1 , —O—(C-Cstraight chain or branched alkyl) claim 1 , and —OH.16. The compound or salt of claim 1 , wherein Ris selected from —C-Cstraight chain or branched alkyl and —S(═O)—CH.17. The compound or salt of claim 1 , wherein two Rbound to the same nitrogen are taken together with the nitrogen atom to form an optionally substituted 5- to 6-membered saturated heterocycle.18. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier or diluent.19. A method for treating a subject suffering from a neurodegenerative disorder or cancer comprising administering to the subject in need thereof a composition of .20. A method of detecting sirtuin-dependence in a biological signal comprising comparing the biological ...

Azaspiro derivatives as trpm8 antagonists

The present invention relates to azaspiro derivatives of the formula (I) or a pharmaceutically acceptable salt thereof or a prodrug thereof, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders which are mediated via the TRPM8 receptor.

Small molecule inhibitors of egfr and pi3k

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a pyrido-pyrimidin-amine structure, a thieno-pyrimidin-amine structure, a thiazolo-pyrimidin-amine structure, a furo-pyrimidin-amine structure, an oxazolo-pyrimidin-amine structure, a purin-amine structure, a pyrrolo-pyrimidin-amine structure, an amino-naphthyridine-carbonitrile structure, an amino-thieno-pyridine-carbonitrile structure, an amino-thiazo-pyridine-carbonitrile structure, an amino-furo-pyridine-carbonitrile structure, an amino-oxazolo-pyridine-carbonitrile structure, an amino-imidazo-pyridine-carbonitrile structure, or an amino-pyrrolo-pyridine-carbonitrile structure which function as dual inhibitors of EGFR proteins and PI3K proteins, and their use as therapeutics for the treatment of cancer and other diseases.

HETEROCYCLIC COMPOUNDS USEFUL AS PIM KINASE INHIBITORS

The present application is concerned with heterocyclic compounds that inhibit the activity of Pim kinases and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancers and other diseases. 134-. (canceled)36. The method of claim 35 , wherein the method is a method of treating an immune disorder.37. The method of wherein the immune disorder is an autoimmune disease.3839-. (canceled)40. The method of claim 36 , wherein the immune disorder is multiple sclerosis claim 36 , rheumatoid arthritis claim 36 , allergy claim 36 , food allergy claim 36 , asthma claim 36 , lupus claim 36 , inflammatory bowel disease or ulcerative colitis.41. The method of claim 35 , wherein the method is a method of treating a myeloproliferative disorder.42. The method of claim 41 , wherein the myeloproliferative disorder is polycythemia vera.43. The method of claim 41 , wherein the myeloproliferative disorder is essential thrombocythemia.44. The method of claim 41 , wherein the myeloproliferative disorder is chronic myelogenous leukemia.45. The method of claim 41 , wherein the myeloproliferative disorder is myelofibrosis.46. The method of claim 41 , wherein the myeloproliferative disorder is primary myelofibrosis.47. The method of claim 41 , wherein the myeloproliferative disorder is post-polycythemia vera/essential thrombocythemia myelofibrosis.48. The method of claim 41 , wherein the myeloproliferative disorder is post-essential thrombocythemia myelofibrosis.49. The method of claim 41 , wherein the myeloproliferative disorder is post-polycythemia vera myelofibrosis.51. The method of claim 35 , wherein Ris selected from ethyl claim 35 , ethynyl claim 35 , phenyl claim 35 , cyclopropyl claim 35 , pyrazolyl claim 35 , pyridyl claim 35 , quinolinyl claim 35 , azetidinyl claim 35 , pyrrolidinyl claim 35 , piperidinyl claim 35 , piperazinyl claim 35 , azepanyl claim 35 , morpholino claim 35 , thiomorpholino claim 35 , indolinyl claim 35 , 3-oxa-8- ...

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

A condensed cyclic compound represented by Formula 1: 2. The condensed cyclic compound of claim 1 , wherein{'sub': 11', '12, 'Rand Rare each independently selected froma phenyl group, a biphenyl group, a terphenyl group, a naphthyl group, a phenanthrenyl group, an anthracenyl group, a triphenylenyl group, a pyrenyl group, and a chrysenyl group; and{'sub': 1', '20', '1', '20, 'a phenyl group, a biphenyl group, a terphenyl group, a naphthyl group, a phenanthrenyl group, an anthracenyl group, a triphenylenyl group, a pyrenyl group, and a chrysenyl group, each substituted with at least one selected from deuterium, —F, —Cl, —Br, —I, a cyano group, a C-Calkyl group, a C-Calkoxy group, and a phenyl group.'}3. The condensed cyclic compound of claim 1 , wherein{'sub': '12', 'and Rare each independently selected froma phenyl group, a biphenyl group, a terphenyl group, and a naphthyl group; anda phenyl group, a biphenyl group, a terphenyl group, and a naphthyl group, each substituted with at least one selected from deuterium, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an iso-butyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an iso-pentyl group, a sec-pentyl group, a tert-pentyl group, an n-hexyl group, an iso-hexyl group, a sec-hexyl group, a tert-hexyl group, a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a pentoxy group, and a phenyl group.4. The condensed cyclic compound of claim 1 , wherein{'sub': '21', 'Ais a benzene group, and'}{'sub': '22', 'Ais selected from a benzene group, a fluorene group, a carbazole group, a dibenzofuran group, a dibenzothiophene group, an indolofluorene group, an indolocarbazole group, an indolodibenzofuran group, an indolodibenzothiophene group, an indenofluorene group, an indenocarbazole group, an indenodibenzofuran group, an indenodibenzothiophene group, a benzofuranofluorene group, a benzofuranocarbazole group, a benzofuranodibenzofuran group, a ...

PARTIALLY SATURATED TRICYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2. 144.-. (canceled)46. The tricyclic compound of claim 45 , wherein Ris selected from hydrogen or methyl.47. The tricyclic compound of claim 45 , wherein Ris selected from hydrogen or fluorine.48. The tricyclic compound of claim 45 , wherein Ris Calkenyl substituted by RRN—.49. The tricyclic compound of claim 45 , wherein Ris (Z)-3-(N claim 45 ,N-diethylamino)prop-1-enyl. This application is a continuation of U.S. patent application Ser. No. 15/014,524, filed Feb. 3, 2016; which is a continuation of U.S. patent application Ser. No. 14/116,023, filed Nov. 6, 2013; which is a national stage filing under U.S.C. §371 of PCT/US2012/036789, filed May 7, 2012; which claims priority to U.S. Provisional Patent Application 61/559,856, filed Nov. 15, 2011; and U.S. Provisional Patent Application 61/483,257, filed May 6, 2011; all of which are incorporated by reference in their entirety.Over 1.1 billion people worldwide are reported to be overweight. Obesity is estimated to affect over 90 million people in the United States alone. Twenty-five percent of the population in the United States over the age of twenty is considered clinically obese. While being overweight or obese presents problems (for example restriction of mobility, discomfort in tight spaces such as theater or airplane seats, social difficulties, etc.), these conditions, in particular clinical obesity, affect other aspects of health, i.e., diseases and other adverse health conditions associated with, exacerbated by, or precipitated by being overweight or obese. The estimated mortality from obesity-related conditions in the United States is over 300,000 annually (O'Brien et al. Amer J Surgery (2002) 184:4S-8S; and Hill et al. (1998) Science, ...

SUBSTITUTED MONO- AND POLYAZANAPHTHALENE DERIVATIVES AND THEIR USE

Disclosed are compounds of formula (I) wherein A is CH or N, B is CR or N; and D is CR; R represents hydrogen, OH or NH; R1 and R2, independently of each other, represent hydrogen, N(R3), halogen, cyano, nitro, R4-C1-C4alkyl, R4-C1-C4halogenoalkyl, OH, R4-C1-C4alkoxy, R4-C1-C4halogenoalkoxy, SH, R4-C1-C4alkythio, R4-C1-C4halogenoalkylthio; R3 represents, independently at each occurrence, hydrogen, R4-C1-C4alkyl or R4-C1-C4halogenoalkyl; R3a represents, independently at each occurrence, hydrogen or C1-C4 alkyl; R4 represents, independently at each occurrence, hydrogen, halogen, cyano, OH, SH, NH, NH(CH) or N(CH); X represents a group of formula -E- or -E-F—, wherein E and F are different from each other and represent a group selected from —C(R3a)2-, —(C═O)—, —NR3a- and —O— and F is linked to Y, with the proviso that if X represents -E-F— one of E or F represents —C(R3a)- or —(C═O)—; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mono- or bicyclic 3 to 11-membered heterocycloalkyl, which may be partially unsaturated, a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, wherein said heterocycloalkyl group and said group comprising at least one heteroaryl cycle comprise one or more heteroatoms selected from nitrogen, oxygen and sulfur and said group Y is either unsubstituted or substituted by one or more substituents and comprises including its substituents one or more than one nitrogen atom having a lone electron pair; and Z represents a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, said heteroaryl cycle comprising one or more heteroatoms selected from nitrogen, oxygen and sulfur, which aryl or heteroaryl group is unsubstituted or substituted by one or more substituents; including tautomers of said compounds, mixtures of two tautomeric forms of said compounds, and pharmaceutically acceptable salts of said compounds, tautomers thereof or mixtures of ...

Pyrazolochlorophenyl compounds, compositions and methods of use thereof

Compounds of Formula I and methods of use as Janus kinase inhibitors are described herein.

HETEROARYL ESTROGEN RECEPTOR MODULATORS AND USES THEREOF

Described herein are heteroaryl compounds with estrogen receptor modulation activity or function having the Formula I, II, and III structures: 2. The compound of claim 1 , wherein A claim 1 , B claim 1 , C claim 1 , and D are each CR.3. The compound of having Formula II claim 1 , wherein Zis CR.4. The compound of having Formula III claim 1 , wherein Zis O or S.5. The compound of having Formula III claim 1 , wherein Zis NR.6. The compound of claim 1 , wherein Cy is phenyldiyl substituted with one or more halo groups.7. The compound of claim 1 , wherein Zis O or NR.8. The compound of claim 7 , wherein Zis NH.9. The compound of claim 1 , wherein Zis O—(C-Calkyldiyl) claim 1 , Yis N claim 1 , and Yis C(R).10. The compound of claim 9 , wherein Yis CH(CHF).11. The compound of claim 1 , wherein Yis CRand Yis NR.12. The compound of claim 11 , wherein Yis NCHCHCHF.13. The compound of claim 1 , wherein Ris C-Calkyl substituted with one or more F.16. A pharmaceutical composition comprising a compound of and at least one pharmaceutically acceptable excipient.17. A method of treating breast cancer claim 1 , lung cancer claim 1 , ovarian cancer claim 1 , endometrial cancer claim 1 , prostate cancer claim 1 , or uterine cancer in a patient having such cancer claim 1 , the method comprising administering a therapeutically effective amount of a compound of .18. The method of claim 17 , further comprising administering an additional therapeutic agent selected from the group consisting of an anti-inflammatory agent claim 17 , an immunomodulatory agent claim 17 , a chemotherapeutic agent claim 17 , an apoptosis-enhancer claim 17 , a neurotropic factor claim 17 , an agent for treating cardiovascular disease claim 17 , an agent for treating liver disease claim 17 , an anti-viral agent claim 17 , an agent for treating blood disorders claim 17 , an agent for treating diabetes claim 17 , and an agent for treating immunodeficiency disorders.19. The method of claim 18 , wherein the additional ...

HETEROARYL ESTROGEN RECEPTOR MODULATORS AND USES THEREOF

Described herein are heteroaryl compounds with estrogen receptor modulation activity or function having the Formula I, II, and III structures: 2. The compound of wherein A claim 1 , B claim 1 , C claim 1 , and D are each CR.3. The compound of wherein one or two of A claim 1 , B claim 1 , C claim 1 , and D are N.4. The compound of having Formula I wherein Zis O.5. The compound of having Formula I wherein Zis S.6. The compound of having Formula I wherein Zis NR.7. The compound of having Formula II wherein Zis CR.8. The compound of having Formula II wherein Zis N.9. The compound of having Formula III wherein Zis O.10. The compound of having Formula III wherein Zis S.11. The compound of having Formula III wherein Zis NR.12. The compound of wherein Cy is phenyldiyl claim 1 , substituted with one or more F.13. The compound of wherein Zis O or NR.14. The compound of wherein Zis NH.15. The compound of wherein Zis O—(C-Cis N claim 1 , Yis —(CH)— claim 1 , and Yis C(R).16. The compound of wherein Yis CH(CHF).17. The compound of wherein Yis CR claim 1 , Yis —(CH)— claim 1 , and Yis NR.18. The compound of wherein Yis NCHCHCHF.19. The compound of wherein Ris C-Calkyl claim 1 , substituted with one or more F.20. The compound of selected from Tables 1a and 1b.21. A pharmaceutical composition comprised of a compound of and a pharmaceutically acceptable carrier claim 1 , glidant claim 1 , diluent claim 1 , or excipient.22. The pharmaceutical composition according to claim 21 , further comprising a therapeutic agent.23. A process for making a pharmaceutical composition which comprises combining a compound of with a pharmaceutically acceptable carrier claim 1 , glidant claim 1 , diluent claim 1 , or excipient.24. A method of treating an ER-related disease or disorder in a patient comprising administering a therapeutically effective amount of the pharmaceutical composition of to a patient with an ER-related disease or condition.25. The method of wherein the ER-related disease or ...

Furo[3,2-b]- and thieno[3,2-b]pyridin derivatives

Compounds of the formula I 2. Compounds according to claim 1 , in which{'sup': 2', '1, 'sub': n', 'p, 'Hetdenotes furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyrimidinyl, triazolyl, tetrazolyl, thiadiazole, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzimidazolyl, 2,3-dihydro-1H-benzimidazolyl, indazolyl, quinolyl, 1,3-benzodioxolyl, benzothiophenyl, benzofuranyl or imidazopyridyl, each of which is unsubstituted or mono- or disubstituted by A, S(O)A, (CYY)-Hetand/or ═O,'}and pharmaceutically usable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.3. Compounds according to claim 1 , in whichAr denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by{'sub': p', 'p', 'p, 'sup': '1', '(CYY)—OY, (CYY)—NYY, (CYY)-Het,'}{'sub': p', 'p', '2', 'm, '(CYY)—COOY, CO(CYY)NH, CO—NYA, CONY(CYY)NYCOOA,'}{'sub': p', 'p, 'sup': 1', '1, 'CONY(CYY)Het, CONH(CYY)NHCOA and/or CO-Het,'}and pharmaceutically usable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.4. Compounds according to claim 1 , in whichX denotes O or S,{'sup': 1', '1', '1, 'sub': n', 'n', 'n', 'n, 'Rdenotes O(CYY)Het, NY(CYY)Het, O(CYY)Cyc or NY(CYY)Cyc,'}{'sup': 2', '2, 'Rdenotes Ar or Het,'}{'sup': '1', 'sub': n', 'n, 'Hetdenotes dihydropyrrolyl, pyrrolidinyl, tetrahydroimidazolyl, dihydropyrazolyl, tetrahydropyrazolyl, tetrahydropyranyl, dihydropyridyl, tetrahydropyridyl, piperidinyl, morpholinyl, hexahydropyridazinyl, hexahydropyrimidinyl, [1,3]dioxolanyl, 2-oxa-6-aza-spiro[3.3]heptanyl, azepanyl, diazepanyl, tetrahydrofuranyl, pyridyl, chromanyl or piperazinyl, each of which is unsubstituted or mono- or disubstituted by Hal, CN, A, COOA, OY, S(O)A, S(O)Ar and/or ═O (carbonyl oxygen),'}{'sup': 2', '1, 'sub': n', 'p, 'Hetdenotes furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyrimidinyl, triazolyl, tetrazolyl, thiadiazole, pyridazinyl, ...

Compound, organic electroluminescent device material, organic electroluminescent device, and electronic equipment

Disclosed are a compound having, as a main skeleton, a polycyclic structure represented by the following general formula (1), a material for organic electroluminescence devices including the compound, an organic electroluminescence device using the compound, and electronic equipment having the organic electroluminescence device mounted thereon. A compound capable of realizing an organic EL device with high emission efficiency, a material for organic electroluminescence devices including the compound, an organic electroluminescence device using the compound, and electronic equipment having the organic electroluminescence device mounted thereon, are provided. In the formula (1), A, L, X 1 to X 16 , R, R A , and R B are those defined in the specification.

Compounds for electronic devices

The present invention relates to compounds of formula (I), to processes for producing the compounds, and to electronic devices containing at least one compound of formula (I).

MATERIALS FOR ELECTRONIC DEVICES

The present application relates to a compound which contains an indenocarbazole group, a particular arylamino group and an electron-deficient group bonded to the indenocarbazole group. The compound is suitable for use in electronic devices, in particular in organic electroluminescent devices. 118.-. (canceled)20. The compound according to claim 19 , wherein the index m is equal to 1.21. The compound according to claim 19 , wherein the index n is equal to 0.22. The compound according to claim 19 , wherein W is equal to CR.23. The compound according to claim 19 , wherein X is equal to C(R).24. The compound according to claim 19 , wherein at least two groups Y in the ring are equal to N claim 19 , and the remaining groups Y are equal to CR.25. The compound according to claim 19 , wherein precisely three groups Y in the ring are equal to N claim 19 , and the remaining groups Y are equal to CR.27. The compound according to claim 19 , wherein at least one of the groups Arand Aris selected claim 19 , identically or differently claim 19 , from the group consisting of biphenyl claim 19 , terphenyl claim 19 , quaterphenyl claim 19 , fluorenyl claim 19 , spirobifluorenyl claim 19 , carbazolyl claim 19 , dibenzofuranyl claim 19 , dibenzothiophenyl claim 19 , naphtyl claim 19 , anthracyl claim 19 , phenantryl claim 19 , chrysenyl claim 19 , triphenylenyl claim 19 , pyrenyl claim 19 , perylenyl claim 19 , each of which may be substituted by one or more radicals R.30. An oligomer claim 19 , polymer or dendrimer containing one or more compounds according to claim 19 , where the bond(s) to the polymer claim 19 , oligomer or dendrimer may be localised at any desired positions in formula (I) which are substituted by Ror R.31. A formulation comprising at least one compound according to and at least one solvent.32. A formulation comprising at least one polymer claim 30 , oligomer or dendrimer according to and at least one solvent.33. An electronic device which comprises the compound ...

COMPOUND FOR ORGANIC OPTOELECTRONIC DIODE, ORGANIC OPTOELECTRONIC DIODE COMPRISING SAME, AND DISPLAY DEVICE

The present invention relates to: a compound for an organic optoelectronic diode, represented by a combination of chemical formulas 1 and 2; an organic optoelectronic diode comprising the same; and a display device comprising the organic optoelectronic diode. The detailed contents of formulas 1 and 2 are the same as those defined in the specification. 3. The compound for an organic optoelectronic diode as claimed in claim 1 , wherein the Xis C-L-Rand Xis C-L-R.4. The compound for an organic optoelectronic diode as claimed in claim 1 , wherein the Rto Rare independently hydrogen claim 1 , deuterium claim 1 , a substituted or unsubstituted C6 to C30 arylamine group claim 1 , a substituted or unsubstituted phenyl group claim 1 , a substituted or unsubstituted biphenyl group claim 1 , a substituted or unsubstituted terphenyl group claim 1 , a substituted or unsubstituted quaterphenyl group claim 1 , a substituted or unsubstituted naphthyl group claim 1 , a substituted or unsubstituted anthracenyl group claim 1 , a substituted or unsubstituted phenanthrenyl group claim 1 , a substituted or unsubstituted pyrenyl group claim 1 , a substituted or unsubstituted triphenylene group claim 1 , a substituted or unsubstituted fluorenyl group claim 1 , a substituted or unsubstituted imidazolyl group claim 1 , a substituted or unsubstituted triazolyl group claim 1 , a substituted or unsubstituted tetrazolyl group claim 1 , a substituted or unsubstituted oxadiazolyl group claim 1 , a substituted or unsubstituted oxatriazolyl group claim 1 , a substituted or unsubstituted thiatriazolyl group claim 1 , a substituted or unsubstituted benzimidazolyl group claim 1 , a substituted or unsubstituted benzotriazolyl group claim 1 , a substituted or unsubstituted pyridinyl group claim 1 , a substituted or unsubstituted pyrimidinyl group claim 1 , a substituted or unsubstituted triazinyl group claim 1 , a substituted or unsubstituted pyrazinyl group claim 1 , a substituted or unsubstituted ...

BICYCLIC LACTAMS AND METHODS OF USE THEREOF

The invention provides novel compounds having the general formula I: 4. A compound according to claim 3 , wherein each Ris selected from the group consisting of hydrogen claim 3 , C-Calkyl claim 3 , C-Chaloalkyl claim 3 , CHCHOCH claim 3 , C-Ccycloalkyl claim 3 , C-Ccycloalkyl substituted by 1 to 2 fluorine atoms claim 3 , CH—(C-Ccycloalkyl) claim 3 , CH—(C-Ccycloalkyl substituted by 1 to 2 fluorine atoms) claim 3 , and CH—(Cheterocyclyl).8. A compound according to claim 6 , wherein Y is O.9. A compound according to claim 6 , wherein Rand Rare each H.15. A compound according to claim 12 , wherein Ris H or methyl; the A ring is 6 membered aryl or 5 membered heteroaryl; Zis C or N; and X is CHor O.16. A compound according to claim 13 , wherein Ris H or methyl; the A ring is 6 membered aryl or 5 membered heteroaryl; Zis C or N; and X is CHor O.17. A compound according to claim 14 , wherein Ris H or methyl; the A ring is 6 membered aryl or 5 membered heteroaryl; Zis C or N; and X is CHor O.18. A compound according to claim 1 , wherein the compound is selected from the compounds of Table 1 claim 1 , Table 2 claim 1 , Table 3 claim 1 , Table 4 and Table 5.19. A compound according to claim 17 , wherein the compound is selected from the compounds of Table 1 claim 17 , Table 2 claim 17 , Table 3 claim 17 , Table 4 and Table 5 which have a Kin the RIP1 kinase inhibitory assay of less than or equal to 0.1 μM.20. A pharmaceutical composition comprising a compound in accordance with and a therapeutically inert carrier.21. A method for the treatment or prophylaxis of a disease or disorder in a patient by administering to the patient a compound of claim 1 , wherein the disease or disorder is selected from the group consisting of prophylaxis of irritable bowel disorders (IBD) claim 1 , irritable bowel syndrome (IBS) claim 1 , Crohn's disease claim 1 , ulcerative colitis claim 1 , myocardial infarction claim 1 , stroke claim 1 , traumatic brain injury claim 1 , atherosclerosis claim ...

BICYCLIC HETEROAROMATIC CARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS

The present disclosure describes bicyclic heteroaromatic carboxamide derivatives, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': '6', 'sub': 6-10', '3-6, 'Cyis unsubstituted or substituted Caryl, unsubstituted or substituted 5-10 membered heteroaryl, unsubstituted or substituted Ccycloalkyl, or unsubstituted or substituted 4-12 membered heterocycloalkyl,'}{'sub': 6-10', '3-6', '2-6', '2-6', '1-6', '2', '2', '2, 'sup': 6', 'Cy6', 'a3', 'a3', 'b3', 'c3', 'd3', 'a3', 'b3', 'c3', 'd3', 'c3', 'd3', 'c3', 'b3', 'c3', 'c3', 'd3', 'c3', 'a3', 'e3', 'c3', 'd3', 'c3', 'e3', 'c3', 'd3', 'b3', 'c3', 'd3', 'b3', 'c3', 'b3', 'c3', 'd3, 'wherein the substituted Caryl, 5-10 membered heteroaryl, Ccycloalkyl or 4-12 membered heterocycloalkyl forming Cyis substituted with 1, 2, 3, 4 or 5 substituents each independently selected from halogen, R, Calkenyl, Calkynyl, Chaloalkyl, CN, OR, SR, C(O)R, C(O)NRR, C(O)OR, OC(O)R, OC(O)NRR, NRR, NRC(O)R, NRC(O)NRR, NRC(O)OR, C(═NR)NRR, NRC(═NR)NRR, S(O)R, S(O)NRR, S(O)R, NRS(O)Rand S(O)NRR.'}4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '1', 'Ris H; and'}{'sup': 2', 'a2', 'a2', 'b2', 'c2', 'd2', 'a2', 'b2', 'c2', 'd2', 'c2', 'd2', 'c2', 'b2', 'c2', 'c2', 'a2', 'c2', 'a2', 'e2', 'c2', 'd2', 'c2', 'e2', 'c2', 'd2', 'b2', 'c2', 'a2', 'b2', 'c2', 'b2', 'c2', 'd2, 'sub': 1-6', '2-6', '2-6', '1-6', '2', '2', '2, 'Ris H, halogen, Calkyl, Calkenyl, Calkynyl, Chaloalkyl, CN, OR, SR, C(O)R, C(O)NRR, C(O)OR, OC(O)R, OC(O)NRR, NRR, NRC(O)R, NRC(O)NRR, NRC(O)OR, C(═NR)NRR, NRC(═NR)NRR, S(O)R, S(O)NRR, S(O)R, NRS(O)Ror S(O)NRR.'}5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein Ris H ...

Bicyclic and Tricyclic Pyrimidine Tyrosine Kinase Inhibitors with Antitubulin Activity and Methods of Treating a Patient

Bicyclic and tricyclic pyrimidine tyrosine kinase inhibitors with antitubulin activity are provided in the present invention. The compositions of the present invention possess dual activity in a single agent of potent vascular endothelial growth factor receptor inhibitory activity as well as antitubulin activity. Water soluble salts of these compositions are also described. Methods of treating a patient having cancer, macular degeneration, and arthritis with the compositions and salts thereof of the present invention are disclosed. 2. (canceled)4. The pharmaceutical composition according to comprising at least one pharmaceutically acceptable carrier.613.-. (canceled)16. A pharmaceutical composition according to comprising at least one pharmaceutically acceptable carrier.18139.-. (canceled)142. A pharmaceutical composition according to comprising at least one pharmaceutically acceptable carrier.143145.-. (canceled) This divisional utility patent application claims the benefit of co-pending U.S. patent application Ser. No. 13/364,930, filed on Feb. 2, 2012, which claims the benefit of U.S. Provisional Patent Application Ser. No. 61/439,470, filed Feb. 4, 2011. The entire contents of U.S. patent application Ser. No. 13/364,930 and U.S. Provisional Patent Application Ser. No. 61/439,470 are incorporated by reference into this divisional utility patent application.1. Field of the InventionThe present invention relates to bicyclic and tricyclic pyrimidine tyrosine kinase inhibitors with antitubulin activity. The compositions of this invention have dual activity of potent vascular endothelial growth factor receptor inhibitory activity along with cytotoxic activity in a single agent. The compositions of this invention may be made into salts that are water soluble for providing orally active antiangiogenic agents. Methods of using these compositions for treating a patient are also provided.2. Description of the Background ArtAntitubulin agents are some of the most successful ...

SUBSTITUTED 1,2-DIHYDRO-3H-PYRAZOLO[3,4-D]PYRIMIDIN-3-ONES

Compounds of Formula (I) are provided herein. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions, including conditions characterized by excessive cellular proliferation, such as breast cancer. 2. A pharmaceutical composition comprising an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent claim 1 , excipient or combination thereof.3. A method for ameliorating or treating a cancer comprising administering an effective amount of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to a subject having the cancer claim 1 , wherein the cancer is selected from a brain cancer claim 1 , a cervicocerebral cancer claim 1 , an esophageal cancer claim 1 , a thyroid cancer claim 1 , a small cell cancer claim 1 , a non-small cell cancer claim 1 , a breast cancer claim 1 , a lung cancer claim 1 , a stomach cancer claim 1 , a gallbladder/bile duct cancer claim 1 , a liver cancer claim 1 , a pancreatic cancer claim 1 , a colon cancer claim 1 , a rectal cancer claim 1 , an ovarian cancer claim 1 , a choriocarcinoma claim 1 , an uterus body cancer claim 1 , an uterocervical cancer claim 1 , a renal pelvis/ureter cancer claim 1 , a bladder cancer claim 1 , a prostate cancer claim 1 , a penis cancer claim 1 , a testicular cancer claim 1 , a fetal cancer claim 1 , Wilms' cancer claim 1 , a skin cancer claim 1 , malignant melanoma claim 1 , a neuroblastoma claim 1 , an osteosarcoma claim 1 , an Ewing's tumor claim 1 , a soft part sarcoma claim 1 , an acute leukemia claim 1 , a chronic lymphatic leukemia claim 1 , a chronic myelocytic leukemia claim 1 , polycythemia vera claim 1 , a malignant lymphoma claim 1 , multiple myeloma claim 1 , a Hodgkin's lymphoma claim 1 , and a non-Hodgkin's lymphoma.4. A method for inhibiting replication of a malignant growth or a tumor comprising ...

FUROQUINOLINEDIONES AS INHIBITORS OF TDP2

Compounds of Formula I and the pharmaceutically acceptable salts thereof are disclosed Formula I. The variables X, X, and Rare disclosed herein. The compounds are useful for treating cancer and related proliferative diseases. Pharmaceutical compositions containing compounds of Formula I and methods of treatment comprising administering compounds of Formula I are also disclosed. 2. The compound or salt of claim 1 , wherein Yis O.3. The compound or salt of wherein{'sup': 1', '1', '7', '9', '10, 'sub': 1', '8', '0', '6', '2', '1', '6, 'Ris hydroxyl, C-Calkoxy or —O—(C-Calkyl)cycloalkyl, in which one or more methylene units in the alkoxy or alkyl portion of Ris optionally and independently replaced with —O— or —N(R)—, and R′ is substituted by 0-3 substituents independently chosen at each occurrence from hydroxyl, halogen, cyano, —COH, —(CO)—O—C-Calkyl, and —W—P(O)YRZR, or'}{'sup': '1', 'Ris the group —O-A-B;'}{'sub': 1', '6', '2', '6', '2', '6', '1', '6', '2', '6', '1', '6', '1', '6', '0', '6', '0', '6', '2', '0', '6', '1', '6', '1', '6', '1', '6', '2', '1', '6', '0', '6, 'sup': 9', '10, 'B is a phenyl, or a 5 or 6 membered heteroaryl having 1, 2, or 3 Nitrogen ring atoms, wherein B is optionally substituted with 0-3 substituents independently chosen from halogen, hydroxyl, cyano, amino, C-Calkyl, C-Calkenyl, C-Calkynyl, C-Calkoxy, C-Calkanoyl, C-Chaloalkyl, C-Chaloalkoxy, —(C-Calkyl)cycloalkyl, —(C-Calkyl)COH, —(C-Calkyl)-(CO)—O—C-Calkyl, —(C-Calkyl)alkoxy, —(C-Calkyl)OH, —SO—C-Calkyl, and —(C-Calkyl)-W—P(O)YRZR;'}{'sup': '2', 'sub': 1', '6', '1', '6', '0', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris halogen, C-Calkyl, C-Chaloalkyl, —(C-Calkyl)cycloalkyl, or phenyl, said phenyl being substituted with 0 to 3 groups chosen independently at each occurrence from halogen, hydroxyl, C-Calkyl, C-Calkoxy, C-Chaloalkyl, and C-Chaloalkoxy; and'}{'sup': 3', '4, 'Rand Rare both hydrogen.'}4. (canceled)5. The compound or salt of claim 1 , wherein{'sup': 2', '7', '8', '2, 'sub ...

PHARMACEUTICAL COMPOSITIONS WHICH INHIBIT FKBP52-MEDIATED REGULATION OF ANDROGEN RECEPTOR FUNCTION AND METHODS OF USING SAME

Pharmaceutical compositions that bind to a predicted FK506 Binding Protein 52 (FKBP52) interaction surface on the androgen receptor hormone binding domain, otherwise known as FKBP52 Targeting Agents (FTAs) are provided. These compositions of the present invention are found to specifically recognize the FKBP52 regulatory surface on the androgen receptor and inhibit FKBP52 from functionally interacting with the androgen receptor. Compositions comprising the pharmaceutical composition, as well as methods of use, treatment and screening are also provided. 17-. (canceled)9. The method of claim 8 , wherein the pharmaceutical composition further comprises one or more anti-androgenic compounds and/or one or more LH-RH agonists.10. The method of claim 9 , wherein the one or more anti-androgenic compound(s) is/are selected from the group consisting of bicalutamide claim 9 , nilutamide claim 9 , and 5-alpha-reductase inhibitors.11. The method of claim 10 , wherein the 5-alpha-reductase inhibitor(s) is/are selected from the group consisting of MK-906 claim 10 , 17-β-N claim 10 ,N-diethylcarbamoyl-4-methyl-4-aza-5-α-androstan-3-one claim 10 , 4-azasteroid claim 10 , 6-methylene-4-pregnene-3 claim 10 ,20-dione claim 10 , and 4-methyl-3-oxo-4-aza-5-α-pregnane-30(s) carboxylate. This application is a divisional of U.S. patent application Ser. No. 13/395,976, filed May 4, 2012, which is a U.S. National Phase of International Patent Application No. PCT/US2010/048705, filed Sep. 14, 2010, which claims the benefit of U.S. Provisional Application No. 61/242,541, filed on Sep. 15, 2009, each of which is incorporated by reference in its entirety herein.Steroid hormone receptors including androgen receptor (AR), glucocorticoid receptor (GR), and the progesterone receptor (PR) require the ordered assembly of various chaperone and cochaperone proteins in order to reach a functional state. The final stage in the receptor maturation process requires the formation of a multimeric complex ...

INHIBITORS OF HIV REPLICATION

Compounds of formula (I) and pharmaceutical compositions thereof: wherein AAand Aare each independently selected from the group consisting of N and CR, wherein Ris an optionally substituted heterocyclyl or an optionally substituted —(C)alkyl-heterocyclyl, Ris an optionally substituted aryl or an optionally subsisted heteroaryl, Ris an optionally substituted aryl, an optionally substituted heterocyclyl or an optionally substituted heteroaryl, useful as an inhibitor of HIV replication. 2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A claim 1 , Aand Aare each independently selected from CR.3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein one of A claim 1 , Aand Ais N and the remaining two of A claim 1 , Aand Aare each independently selected from CR.4. The compound according to claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Ris heterocyclyl or —(C)alkyl-heterocyclyl claim 3 , wherein each said heterocyclyl and —(C)alkyl-heterocyclyl is optionally substituted with 1 to 2 substituents each independently selected from —(C)alkyl; and wherein said heterocyclyl is a 5- claim 3 , 6- or 7-membered heterocycle containing one oxygen atom.6. The compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris a 5- or 6-membered heteroaryl optionally substituted with 1 to 2 substituents each independently selected from the group consisting of —(C)alkyl claim 5 , halo claim 5 , —(C)haloalkyl claim 5 , —N(R)(R) and —O(C)alkyl;{'sup': '21', 'sub': '1-3', 'Ris H or —(C)alkyl; and'}{'sup': '22', 'sub': 1-3', '2-4, 'Ris H, —(C)alkyl or —(C)alkenyl.'}8. The compound according to claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein Ris independently in each instance selected from the group consisting of H claim 7 , halo claim 7 , —CN claim 7 , —O(C)alkyl and —(C)alkyl optionally substituted with —O(C ...

ISOINDOLINE COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE

Isoindoline sigma-2 receptor antagonist compounds, pharmaceutical compositions comprising such compounds, and methods for inhibiting Abeta-associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology are provided. 137.-. (canceled)40. The method of wherein the dose is about 0.1 mg/kg/day to about 10 mg/kg/day.41. The method of wherein the dose is about 0.2 mg/kg/day to about 5 mg/kg/day.42. The method of wherein the total daily dose is administered in a single dose.43. The method of wherein the total daily dose is administered in multiple doses per day.44. The method of wherein the compound is formulated in a capsule or tablet.45. The method of wherein the capsule or tablet comprises 0.1 mg/kg/day to about 10 mg/kg/day of the compound or a pharmaceutically acceptable salt thereof.46. The method of wherein the capsule or tablet comprises 0.2 mg/kg/day to about 5 mg/kg/day of the compound or a pharmaceutically acceptable salt thereof.47. The method of wherein the compound is administered orally.50. The method of wherein the total daily dose of the compound administered is about 0.1 mg/kg/day to about 10 mg/kg/day.51. The method of wherein the total daily dose of the compound administered is about 0.2 mg/kg/day to about 5 mg/kg/day.52. The method of wherein the dose is administered in a single dose.53. The method of wherein the dose is administered in multiple doses per day.54. The method of wherein the pharmaceutical composition is a capsule or tablet.55. The method of wherein the capsule or tablet comprises about 0.1 mg/kg/day to about 10 mg/kg/day of the compound or a pharmaceutically acceptable salt thereof.57. The method of wherein the total daily dose is about 0.2 mg/kg/day to about 5 mg/kg/day.58. The method of wherein the pharmaceutical composition is administered orally. The present application is a Continuation of ...

ION CHANNEL INHIBITOR COMPOUNDS FOR CANCER TREATMENT

The present invention concerns a compound of following general formula (I): 4. The method according to , wherein in formula (III) Cyis an aliphatic ring or heteroaliphatic ring such as defined in , said aliphatic or heteroaliphatic rings optionally being fused to a heteroaryl ring.9. The method according to claim 2 , where Ris H.10. The method according to claim 2 , where Rand Rare H.12. The method according to wherein the cancer is breast cancer.14. A medicinal product comprising the compound according to . The subject of the present invention concerns novel compounds in particular of pyridopyrimidine type having ion channel inhibitory properties, in particular of channel SK3. A further subject is the use of said compounds for cancer treatment.The major therapies for early presentations of cancers are surgery and/or radiotherapy, with the adjunction of hormone therapy for breast cancer, and chemotherapy. The onset of visceral metastases after breast or prostate cancer generally corresponds to progression onto a palliative step. Patient survival time and quality depend upon the sensitivity of the disease to anticancer treatments. The treatment and prevention of metastases call for novel approaches. At the current time, various potential targets of biological routes are being researched to reach this objective.In women, breast cancer represents the major cause of deaths by cancer over the world. Breast cancer has marked bony tropism and steroid hormone dependency, factors which promote tumour growth, cell survival and cell invasion.When a cancer becomes metastatic, it is often life-threatening. During tumour growth (primary tumour) cancer cells detach themselves from the primary tumour and migrate, either via the lymphatic pathway (the lymph nodes are connected together by thin channels, the network forming the lymphatic system), or via the blood pathway. This ability of a cancer to metastasize is most certainly determined by a set of biological factors which, at the ...

RHO-ASSOCIATED PROTEIN KINASE INHIBITOR, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AS WELL AS PREPARATION METHOD AND USE THEREOF

The present invention relates to a Rho-associated protein kinase inhibitor of Formula (I), a pharmaceutical composition comprising the same, a preparation method thereof, and use thereof for the prevention or treatment of a disease mediated by the Rho-associated protein kinase (ROCK). 2. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , ester claim 1 , stereoisomer claim 1 , polymorph claim 1 , solvate claim 1 , N-oxide claim 1 , isotopically labeled compound claim 1 , metabolite or prodrug thereof claim 1 , wherein X and Y are each independently selected from the group consisting of a direct bond claim 1 , C(═O) claim 1 , O claim 1 , S claim 1 , S(═O) claim 1 , S(═O)and NH claim 1 , and at least one of X and Y is a direct bond.10. A pharmaceutical composition comprising a prophylactically or therapeutically effective amount of the compound according to or a pharmaceutically acceptable salt claim 1 , ester claim 1 , stereoisomer claim 1 , polymorph claim 1 , solvate claim 1 , N-oxide claim 1 , isotopically labeled compound claim 1 , metabolite or prodrug thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , and the pharmaceutical composition is preferably in the form of a solid claim 1 , semi-solid claim 1 , liquid claim 1 , or gas preparation.11. A method of inhibiting a Rho-associated protein kinase (ROCK) claim 1 , preferably ROCK2 claim 1 , comprising administering an effective amount of the compound according to or a pharmaceutically acceptable salt claim 1 , ester claim 1 , stereoisomer claim 1 , polymorph claim 1 , solvate claim 1 , N-oxide claim 1 , isotopically labeled compound claim 1 , metabolite or prodrug thereof.12. A method for the prevention or treatment of a disease mediated by the Rho-associated protein kinase (ROCK) claim 1 , comprising administering to a subject in need thereof an effective amount of the compound according to or a pharmaceutically acceptable salt claim 1 , ester claim 1 , ...

1,5-DISUBSTITUTED 1,2,3-TRIAZOLES ARE INHIBITORS OF RAC/CDC42 GTPASES

Compounds are disclosed that inhibit RhoGTPases that are useful for inhibiting hyperprofilerative and neoplastic diseases. Specifically, the compounds inhibit the GTPases Rac and Cdc42 that are overactive or overexpressed in signaling pathways in cancer and metastasis. Methods for treatment of cancer and hyperproliferative diseases are disclosed. 2. The process of claim 1 , wherein the compound of formula (VI) claim 1 ,{'br': None, 'sub': '3', 'YM-≡—R\u2003\u2003(VI)'} {'br': None, 'sub': '3', '≡—R\u2003\u2003(VIa)'}, 'is prepared by contacting a compound of the formula (VIa),'} {'br': None, 'sup': 'B', 'RYX \u2003\u2003(VII)'}, 'with a compound of the formula (VII),'}{'sup': 'B', 'sub': 1', '6, 'wherein Ris C-Calkyl, M is a metal, and Y is a halogen.'}3. The process of claim 1 , wherein M is magnesium.4. The process of claim 1 , wherein Y is bromo or chloro.5. The process of claim 1 , wherein Y is absent and M comprises zinc.6. The process of claim 5 , wherein the zinc is diethyl zinc.7. The process of claim 1 , wherein the process further comprises a base.8. (canceled)9. The process of claim 1 , wherein the catalyst is a ruthenium catalyst.10. The process of claim 1 , wherein the catalyst is (Cp*RuCl).11. The process of claim 1 , wherein the step of contacting is performed in the presence of a polar solvent.12. The process of claim 11 , wherein the polar solvent is THF claim 11 , DMF claim 11 , dichloromethane claim 11 , EtO claim 11 , diglyme claim 11 , or a mixture thereof.13. The process of claim 1 , wherein the process is carried out at an elevated temperature claim 1 , wherein the elevated temperature is at least 35° C.15. The process of claim 14 , wherein the acid is a mineral acid.16. The process of claim 15 , wherein the mineral acid is sulfuric acid.17. The process of claim 14 , wherein the azide is sodium azide.18. The process of claim 14 , wherein step (a) further comprises sodium nitrite.19. (canceled)20. The process of claim 1 , wherein A and B are ...

HETEROCYCLIC COMPOUND AND ORGANIC LIGHT EMITTING DEVICE USING THE SAME

Disclosed are a heterocyclic compound represented by Formula 1 and an organic light emitting device using the same. The heterocyclic compound is used as a material for hole injection layer, hole transport layer, hole injection and transport layer, light emission layer, electron transport layer, or electron injection layer of the organic light emitting device and provides improved efficiency, low driving voltage, and improved lifetime characteristic. 6. The compound of claim 1 , wherein Ris hydrogen or a substituted or unsubstituted Calkyl.11. An organic light emitting device comprising: a first electrode; a second electrode provided to face the first electrode; and at least one layer of an organic material layer provided between the first electrode and the second electrode claim 1 , wherein the at least one layer of the organic material layer includes the compound according to .12. The organic light emitting device of claim 11 , wherein the organic material layer including said compound is a light emitting layer.13. The organic light emitting device of claim 12 , wherein the compound is a host material in the light emitting layer.14. The organic light emitting device of claim 13 , wherein the light emitting layer further includes a dopant material.15. The organic light emitting device of claim 11 , wherein the organic material layer including said compound is an electron injection layer; an electron transport layer claim 11 , or a layer simultaneously performing electron injection and electron transport. This application is a National Phase entry pursuant to 35 U.S.C. § 371 of PCT/KR2018/008233 filed on Jul. 20, 2018, and claims priority to and the benefit of Korean Patent Application No. 10-2017-0092174 filed on Jul. 20, 2017 and Korean Patent Application No. 10-2018-0084348 filed on Jul. 19, 2018 with the Korean Intellectual Property Office, the disclosures of which are incorporated herein by reference in their entirety.The present disclosure relates to a novel ...

Condensed cyclic compound and organic light-emitting device including the same

A condensed cyclic compound and an organic light-emitting device including the condensed cyclic compound are provided.