СЕРУСОДЕРЖАЩИЕ СОЕДИНЕНИЯ, ДЕЙСТВУЮЩИЕ КАК ИНГИБИТОРЫ СЕРИНОВОЙ ПРОТЕАЗЫ NS3 ВИРУСА ГЕПАТИТА С

Настоящее изобретение относится к новым соединениям, обладающим ингибирующей активностью в отношении протеазы HCV, равно как и к способам получения таких соединений. В другом варианте выполнения изобретение относится к фармацевтическим композициям, содержащим такие соединения, равно как и к способам их применения для лечения нарушений, связанных с протеазой HCV. 10 н. и 38 з.п. ф-лы, 5 табл.

СОЕДИНЕНИЯ И СПОСОБЫ ИНГИБИРОВАНИЯ ВЗАИМОДЕЙСТВИЯ БЕЛКОВ BCL С КОМПОНЕНТАМИ СВЯЗЫВАНИЯ

Настоящее изобретение относится к гетероциклическим соединениям формулы I ! ! где Y означает -(С=O)-, Х означает -N(R10)-, А означает -C(A1)(A2)-, В означает О, S, -(С=O)- или характеризуется формулой ! ! где D означает N или СR10 и где значения остальных заместителей раскрыты в формуле изобретения. Соединения формулы 1, а также композиции на его основе обладают способностью ингибировать белки семейства bcl-2, что обуславливает возможность применения таких соединений и композиций при лечении или модулировании нарушений, ассоциированных с гиперпролиферацией, таких как рак. 7 н. и 13 з.п. ф-лы.

КАРБОКСАМИДНЫЕ ПРОИЗВОДНЫЕ ПИРРОЛИДИНА ИЛИ ПИПЕРИДИНА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ИНГИБИРОВАНИЯ АГРЕГАЦИИ ТРОМБОЦИТОВ

Изобретение относится к новым производным пирролидина или пиперидина ф-лы (I), их энантиомерам и фармацевтически приемлемым солям где R10 - Н или C(O)N(R1)YZ, R1 - Н, Y - (СН2)р, (CH2)qCH(R3) или CH(R3)(CH2)q, R3 - арил, аралкил или гетероарил, q = 1-3, р = 2 или 3, Z - CO2H, СО2-алкил или 5-тетразол, Х-С(O), М-(СН2)n, или пиперидин-1-ил, m = 2, n = 2, R5 - Н, А выбирают из пиперидин-2-ила, пиперидин-3-ила, пиперидин-4-ила или N-замещенного пиперидина. Соединения ф-лы (I) ингибируют агрегацию тромбоцитов и могут найти применение в медицине. 3 с. и 2 з.п. ф-лы, 6 табл.

ПРОТИВОВИРУСНЫЕ СОЕДИНЕНИЯ

Изобретение относится к новым соединениям формулы I, приведенной ниже, или его фармацевтически приемлемым солям. Соединения эффективны для ингибирования репликации вируса гепатита С ("HCV"). Описан способ их получения.,где:A независимо от B означает фенил,, или, иB независимо от A означает фенил,, или,и значения Z, Y, D, L, L, L, Z, Zприведены в формуле изобретения. 6 н. и 11 з.п. ф-лы, 3 табл., 8 ил., 177 пр.

ИНГИБИТОРЫ ДИПЕПТИДИЛПЕПТИДАЗЫ IV

Предложены соединения общей формулы (1): где Х1 выбирают из атома серы и метиленовой группы; Х2 выбирают из О, S и метилена; X3 обозначает либо NR5, либо карбонильную группу; R1обозначает либо атом водорода, либо нитрильную группу; R2 и R3 выбирают независимо из Н и C1-С6 алкила; R4 обозначает R4A, когда X3 обозначает NR5, и R4B, когда X3 обозначает карбонильную группу; R4A выбирают из R6R7NC(=O), R6R7NC(=S), R8(CH2)qC(=O), R8(CH2)qC(=S), R8(CH2)qSO2 и R8(CH2)qOC(=O); R4B обозначает R6R7N; R5 обозначает Н; R6 и R7 выбирают независимо из R8(CH2)q или вместе они образуют -(CH2)2-Z1-(CH2)2- или -CHR9-Z2-CH2-CHR10-; R8 выбирают из Н, C1-C4 алкила, циклоалкила, конденсированного с бензольным кольцом, ацила, диалкилкарбамоила, диалкиламино, N-алкилпиперидила, необязательно замещенного арила, необязательно замещенного α -алкилбензила, необязательно замещенного ароила, необязательно замещенного арилсульфонила и необязательно замещенного гетероарила, представляющего собой моноциклическую пяти- и ...

ИНГИБИТОРЫ ТРОМБИНА И ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ ДЛЯ ИХ ПОЛУЧЕНИЯ

Описываются соединения формулы (I), а также их соли с физиологически приемлемыми кислотами и их стереоизомеры, где заместители имеют указанные в описании значения. Также в изобретении описываются промежуточные продукты формулы (II) для их получения. Соединения пригодны для борьбы с заболеваниями в системе свертывания крови, а также могут служить для профилактики тромбоза, например после хирургических вмешательств. 2 с.п. ф-лы.

СПОСОБ ПОЛУЧЕНИЯ N-ГИДРОКСИ-3-[4-[[[2-(2-МЕТИЛ-1Н-ИНДОЛ-3-ИЛ)ЭТИЛ]АМИНО]МЕТИЛ]ФЕНИЛ]-2Е-2-ПРОПЕНАМИДА И ИСХОДНЫХ МАТЕРИАЛОВ ДЛЯ НЕГО

Изобретение относится к способу получения N-гидрокси-3-[4-[[[2-(2-метил-1Н-индол-3-ил)этил]амино]метил]фенил]-2Е-2-пропенамида, включающего: (а) объединение при перемешивании гидроксида натрия и гидрохлорида метилового эфира (Е)-3-(4-{[2-(2-метил-1Н-индол-3-ил)этиламино]метил}фенил)акриловой кислоты в растворе с получением смеси при температуре ниже около -10°С; и затем (б) добавление гидроксиламина к полученной смеси с получением N-гидрокси-3-[4-[[[2-(2-метил-1Н-индол-3-ил)этил]амино]метил]фенил]-2Е-2-пропенамида, после чего при необходимости проведение (в) кристаллизации N-гидрокси-3-[4-[[[2-(2-метил-1Н-индол-3-ил)этил]амино]метил]фенил]-2Е-2-пропенамида и необязательно (г) выделение целевого продукта. Способ снижает образование побочных продуктов и позволяет получать целевой продукт с чистотой, достаточной для производства лекарственных препаратов. 15 з.п. ф-лы, 5 пр.

ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ ИМИДАЗОЛИДИНА, СПОСОБ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКИЙ ПРЕПАРАТ

Изобретение относится к замещенным производным имидазолидина формулы 1 где W обозначает R1 -A-C(R13) или где кольцевая система может быть замещена 1, 2 или 3 одинаковыми или различными заместителями R13 и где L обозначает C(R13) и ml и m2 независимо друг от друга означают 0, 1, 2, 3 или 4, причем сумма ml + m2 равна 3 или 4; Y обозначает карбонильную группу; A обозначает прямую связь или двухвалентный остаток фенилена, В обозначает двухвалентный (С1–C6 )-алкиленовый остаток, причем (С1 –C6)-алкиленовый остаток незамещен или замещен одним или несколькими одинаковыми или различными остатками из ряда (С1–C8 )-алкил и (С3–C10 )-циклоалкил-(С1–C6)-алкил, Е обозначает R10CO, HCO или R8O-CH2; R - Н или (C1-C8 )-алкил, (С3–C12 )-циклоалкил-(С1–C8)-алкил или в случае необходимости замещенный (С6–C14)-арил, причем все остатки R независимо друг от друга могут быть одинаковыми или различными; R1 - Н, (C1-C10)-алкил, который, при необходимости, может быть однократно или многократно замещен фтором, или ...

БЕНЗИЛАМИНОВЫЕ ПРОИЗВОДНЫЕ КАК ИНГИБИТОРЫ КАЛЛИКРЕИНА ПЛАЗМЫ

Настоящее изобретение относится к соединениям формулы (I), композициям, содержащим такие соединения; применению таких соединений в терапии для лечения или предотвращения заболеваний или состояний, при которых предполагается активность калликреина плазмы; и способам лечения пациентов с помощью таких соединений; где Rвыбирают из Н, алкила, -СОалкила, -СОарила, -СОгетероарила, -(СН)ОН, -(СН)COOR, -(СН)CONH, -SOалкила, -SОарила, -SO(СН)R, -СО(СН)R, -СОциклоалкила, -COCH=CHR, -СО(СН)NHCO(СН)kRи -CONRR; Rвыбирают из Н и алкила; Rвыбирают из алкила, -(СН)арила, -(СН)гетероарила, (СН)циклоалкила, -СН(циклоалкила)и -(СН)арил-O-(СН)-арила; Rи Rнезависимо выбирают из Н и алкила; Rвыбирают из Н и ОН; или Rи R, вместе с атомами, к которым они присоединены, могут связываться с образованием 5- или 6-членной азациклоалкильной структуры; Rвыбран из Н и галогена; Rвыбран из Н, алкила, галогена и CF; Rпредставляет собой арил или гетероарил; Rпредставляет собой Н или алкил; а, b, с, d, е, f, g, h, i, j, l ...

ИНГИБИТОРЫ ВИРУСА ГЕПАТИТА С

Изобретение относится к ингибиторам вируса гепатита С, имеющим общую формулу где R1 обозначает C1-8алкил, С3-7циклоалкил; m обозначает 2; n обозначает 1; R2 обозначает Н, C1-6алкил, С2-6алкенил, каждый из которых, необязательно, замещен галогеном; R3 обозначает C1-8алкил, необязательно имеющий следующий заместитель: С6-10арил, C7-14алкиларил, C1-6 алкокси, карбокси, гидрокси, C7-14алкиларилокси, С2-6алкиловый сложный эфир, C8-15алкилариловый сложный эфир; С3-7алкенил, С3-7циклоалкил или C4-10алкилциклоалкил, где циклоалкил или алкилциклоалкил, необязательно, имеют заместитель: C1-6алкил; Y обозначает Н или C1-6алкил, при условии, что если R4 или R5 обозначает Н, тогда Y обозначает Н; В обозначает Н, R4-(C=O)-, R4O(C=O)-, R4-N(R5)-C(=O)-; R4 обозначает (i) C1-10алкил, необязательно имеющий следующий заместитель: фенил, 1-3 атома галогена, гидрокси, -OC(O)C1-6алкил, C1-6алкокси; (ii) C3-7циклоалкил, С3-7циклоалкокси или C4-10алкилциклоалкил; (iii) С6-10арил или C7-16арилалкил, каждый из которых ...

ИНГИБИТОРЫ ПРОТЕАЗ, РАСЩЕПЛЯЮЩИХ ЗА ПРОЛИНОМ

Изобретение относится к соединениям формулы 1 и их фармацевтически приемлемым солям в качестве ингибиторов пост-пролиновых аминопептидаз, а также к фармацевтической композиции на их основе и применение для изготовления такой композиции, и способу ингибирования с их использованием. Соединения могут найти применение для лечения заболеваний, опосредованных активностью пост-пролиновых аминопептидаз, таких как диабет типа II и нарушеной толерантности к глюкозе. В общей формуле 1 либо G1 представляет собой -CH2-Х2-(CH2)а-G3, и G2 представляет собой Н, либо G2представляет собой -CH2-(CH2)a-G3, и G1 представляет собой Н; G3 выбран из группы согласно общей формуле 2, группы согласно общей формуле 3 и группы согласно общей формуле 4; а равно 0, 1 или 2; b равно 1 или 2; X1 выбран из СН2, S, CF2, CHF и О; X2выбран из CH2; X3, X4 и X5 выбраны из N; X6 выбран из NH; X7 выбран из NH; R1 выбран из Н и CN; R2 представляет собой Н; R3 выбран из Н, Cl, ОН, NH2, NH-C1-С10алкила и N(С1-С10алкил)2; R4, R5, ...

СПОСОБ ПОЛУЧЕНИЯ N-ЗАМЕЩЕННЫХ 2-ЦИАНОПИРРОЛИДИНОВ

Изобретение относится к усовершенствованному способу получения N-(N′-замещенного глицил)-2-цианопирролидина формулы IA и IB: ! ! или ! ! где R′ представляет собой гидрокси, С1-7алкоксигруппу, С1-8алканоилоксигруппу или R′′′R′′′′N-C(O)O-, где R′′′ и R′′′′ независимо представляют собой С1-7алкил или фенил, который является незамещенным или замещенным заместителем, выбранным из С1-7алкила, С1-7алкоксигруппы, галогена и трифторметила, и где R′′′ дополнительно представляет собой водород; или R′′′ и R′′′′ вместе представляют собой С3-6алкилен; и R′′ представляет собой водород; или R′ и R′′ независимо представляют собой C1-7алкил; в форме свободного основания или в форме кислотной аддитивной соли, включающий ! (а) реакцию соединения формулы (V) ! ! где, независимо друг от друга, X1 и Х3 представляют собой галоген; Х2 представляет собой галоген, ОН, О-С(=О)-СН2Х3, -О-SО2-(С1-8)алкил или -O-SO2-(арил), ! с L-пролинамидом в присутствии диметилформамида, последующую ! (б) реакцию полученного соединения ...

ПРОИЗВОДНОЕ ПИРРОЛИДИН-3-ИЛУКСУСНОЙ КИСЛОТЫ

Изобретение относится к соединениям формулы (1),где R представляет собой Cалкильную группу, незамещенную или содержащую 1-3 заместителя, выбранных из группы заместителей А, Cциклоалкильную группу, незамещенную или содержащую 1-3 заместителя, выбранных из группы заместителей А, или Сциклоалкенильную группу, незамещенную или содержащую 1-3 заместителя, выбранных из группы заместителей А, X представляет собой Cалкильную группу, Y и Ζ являются одинаковыми или отличными друг от друга, и каждый из них представляет собой атом галогена или Cалкильную группу, незамещенную или содержащую 1-3 заместителя, выбранных из группы заместителей В, n равняется 0 или 1, при этом группа заместителей А состоит из атомов галогена, и группа заместителей В состоит из атомов галогена, обладающим ингибирующим эффектом на путь фракталкин-CX3CR1. 14 н. и 6 з.п. ф-лы, 4 ил., 5 табл., 14 пр.

БИЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ ВЗАИМОДЕЙСТВИЯ/АКТИВАЦИИ PD1/PD-L1

Изобретение относится к соединениям формулы I, их стереоизомерам и фармацевтически приемлемым солям, которые являются ингибиторами активации PD-1/PD-L1. В формуле (I) X1 выбирают из -CH2O-; R4 выбирают из водорода; X выбирают из CR3 или N; R1, R2, R3, R6 и R7 независимо выбирают из водорода, галогена, C1-6 алкила, (4-10-членный гетероциклоалкил)-C1-4 алкила-, ORa или C(O)ORa, где C1-6 алкил и (4-10-членный гетероциклоалкил)-C1-4 алкил- независимо необязательно замещены 1, 2 или 3 Rb заместителями, и 4-10-членный гетероциклоалкил имеет 1-3 гетероатома, выбранных из азота и кислорода, и является моно- или бициклическим; Ra выбирают из C1-6 алкила, C1-4 галоалкила, C6-10 арил-C1-4 алкила-, C3-10 циклоалкил-C1-4 алкила-, (5-10-членный гетероарил)-C1-4 алкила- или (4-10-членный гетероциклоалкил)-C1-4 алкила-, где C1-6 алкил, C6-10 арил-C1-4 алкил-, C3-10 циклоалкил-C1-4 алкил-, (5-10-членный гетероарил)-C1-4 алкил- и (4-10-членный гетероциклоалкил)-C1-4 алкил- независимо необязательно замещены ...

КОНЪЮГАТ ЛИГАНДА С ЦИТОТОКСИЧЕСКИМ ЛЕКАРСТВЕННЫМ СРЕДСТВОМ, СПОСОБ ЕГО ПОЛУЧЕНИЯ И ПРИМЕНЕНИЕ

Изобретение относится к конъюгату лиганда с цитотоксическим лекарственным средством общей формулы PC-L-D, способу его получения и содержащим его фармацевтическим композициям для получения лекарственных средств для лечения рака. 7 н. и 11 з.п. ф-лы, 5 таб., 53 пр.

ПРОИЗВОДНОЕ БЕНЗИЛФЕНИЛОВОГО ЭФИРА, СПОСОБ ЕГО ПОЛУЧЕНИЯ И ЕГО ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И ПРИМЕНЕНИЕ

Настоящее изобретение относится к производному бензилфенилового эфира, представленному формулой (IA-1), или его фармацевтически приемлемой соли или стереоизомеру, а также к конкретным производным бензилфенилового эфира, структуры которых представлены в формуле изобретения, или их фармацевтически приемлемой соли или стереоизомеру, ингибирующим взаимодействие PD-1/PD-L1. Также изобретение относится к способу получения заявленных соединений, фармацевтической композиции и применению заявленных соединений.В формуле IA-1 R2выбран из циано и метилсульфонила; R3выбран из;X выбран из водорода и хлора. 6 н. и 4 з.п. ф-лы, 1 табл., 28 пр.

КРИСТАЛЛИЧЕСКИЕ ФОРМЫ КОМПЛЕКСОВ, ПОЛЕЗНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ SGLT2, И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

Изобретение относится к кристаллической форме комплекса (2S,3R,4R,5S,6R)-2-(4-хлор-3-(4-(2-иклопропоксиэтокси)бензил)фенил)-6-(гидроксиметил)тетрагидро-2Н-пиран-3,4,5-триол, бис(L-пролин), характеризующаяся паттерном дифракции рентгеновских лучей на порошке, включающим пики при 4,08, 17,19 и 21,12 градусов 2θ (±0.05 градусов 2θ), где указанный паттерн дифракции рентгеновских лучей на порошке получают с применением излучения CuK. Предоставленный комплекс обладает ингибиторным действием на зависимый от натрия транспортер SGLT. 4 н. и 3 з.п. ф-лы, 1 табл., 3 ил., 7 пр.

СПОСОБ СЕЛЕКТИВНОГО ПОЛУЧЕНИЯ изо-ПРОПИЛ 5'-АРИЛ-1'Н-ПИРРОЛИДИНО[3',4':1,9](С-I)[5,6]ФУЛЛЕРЕН-2'-КАРБОКСИЛАТОВ

Изобретение относится к области органического синтеза, а именно к способу получения фуллеропирролидинов, которые могут найти применение в качестве комплексообразователей, сорбентов, биологически активных соединений, а также при создании новых материалов с заданными электронными, магнитными и оптическими свойствами. Способ селективного получения изо-пропил 5'-арил-1'H-пирролидино[3',4':1,9](С-I)[5,6]фуллерен-2'-карбоксилатов общей формулы (1) характеризуется тем, что С-фуллерен взаимодействует с этилизоцианоацетатом формулы EtOCCHN≡Cв хлорбензоле под действием катализатора Ti(OiPr)в присутствии ArMgBr (где Ar=Ph, 2-MePh), взятыми в мольном соотношении С:изоцианоацетат:Ti(OiPr):ArMgBr = 1:(2-6):(1-5):(6-10), при температуре 100°С в течение 5-30 мин. 1 табЛ., 1 пр.

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Изобретение относится к области органической химии, а именно к соединению формулы 1 или его фармацевтически приемлемой соли, где R1 представляет собой C2-C5 алкил. Также изобретение относится к фармацевтической композиции на основе соединения формулы 1, ее применению для получения лекарственного средства и к способу лечения или профилактики указанных заболеваний. Технический результат: превосходная агонистическая активность в отношении рецепторов меланокортина, проявляемая соединением формулы 1, что может быть использовано для предотвращения или лечения ожирения, диабета, воспалений и эректильной дисфункции. 10 н. и 9 з.п. ф-лы, 10 табл., 16 пр. Формула 1 ...

Применение (5-(метоксикарбонил)-[1,1'-бифенил]-3-ил)-L-пролина в качестве средства, обладающего противотуберкулезной активностью

Изобретение может быть использовано в области фармакологии и медицины, в частности фтизиатрии, и относится к новому применению (5-(метоксикарбонил)-[1,1'-бифенил]-3-ил)-L-пролина в качестве средства, обладающего противотуберкулезной активностью. 1 табл., 2 пр.

ПРОИЗВОДНЫЕ КАРБАПЕНЕМА, ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ И ГИДРОЛИЗУЕМЫЕ IN VIVO ЭФИРО (ВАРИАНТЫ), СПОСОБ ИХ ПОЛУЧЕНИЯ (ВАРИАНТЫ), ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ АНТИБАКТЕРИАЛЬНОЙ АКТИВНОСТЬЮ, ПРОИЗВОДНЫЕ ПИРРОЛИДИН-4-ИЛТИОЛА И ЗАЩИЩЕННЫЕ ПРОИЗВОДНЫЕ ПИРРОЛИДИНА-4-ИЛТИОЛА

Изобретение относится к карбапенемам, предназначенным для использования в медицине для терапевтических целей. Изобретением является соединение формулы (I): в котором R является водородом, R1 является оксиметилом или 1-оксиэтилом; R2 и R3 являются водородом или (C1 - C4)алкилом; R4 и R5 одинаковые или различные, представляют собой водород, галоген, амино, цианогруппу, (C1 - C4)алкил, гидроксигруппу, карбоксигруппу, (C1 - C4)алкоксигруппу, (C1 - C4)алкоксикарбонил, карбамоил, (C1 - C4)алкилкарбамоил, ди (C1 - C4)алкилкарбомоил, трифторметил, сульфокислотную группу, (C1 - C4)алкиламино, ди (C1 - C4)алкиламиногруппу, (C1 - C4 )алканоиламиногруппу, (C1 - C4)алканоил[N - (C1 - C4)алкил]аминогруппу, (C1 - C4)алкансульфонамидогруппу, (C1 - C4)алкилсульфинилгруппу, (C1 - C4)алкилтиогруппу и (C1 - C4 )алкилсульфонилгруппу при условии, что в орто-положении к -N-R3 группе нет гидроксильного или карбоксильного заместителя, или его фармацевтически приемлемую соль или его гидролизуемый in vivo эфир. Способ ...

ПРОИЗВОДНЫЕ ПЕПТИДОВ, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМКОМПОЗИЦИЯ И СПОСОБ ИНГИБИРОВАНИЯ ТРОМБИНА У МЛЕКОПИТАЮЩЕГО

Пептидное производное общей формулы I X - Y - NH - (CH2)r - G или его фармацевтически приемлемая соль, или его сольват, где значения X, Y, r, G указаны в п.1 формулы изобретения, которое может найти применение при ингибировании тромбина у млекопитающего. Описывается также способ их получения, фармкомпозиция и способ ингибирования тромбина у млекопитающего. 4 с. и 2 з.п. ф-лы, 2 табл.

ПРОЛЕКАРСТВА КЕТАМИНА, ЕГО КОМПОЗИЦИИ И ПРИМЕНЕНИЯ

Изобретение относится к соединениям или к их фармацевтически приемлемым солям, являющимся пролекарствами кетамина, которые выбраны из следующих структур:Изобретение также относится к фармацевтической композиции, модулирующей противодействие рецептора NMDA, на основе указанных соединений. Технический результат – получены новые соединения и фармацевтическая композиция на их основе, которые могут найти применение в медицине для лечения заболеваний, связанных с рецептором NMDA, включая депрессию и боль. 8 н. и 7 з.п. ф-лы, 6 табл., 109 пр.

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

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

ИНГИБИТОРЫ ФЕРМЕНТАТИВНОЙ АКТИВНОСТИ РОТАМАЗЫ, ЯВЛЯЮЩИЕСЯ МАЛЫМИ МОЛЕКУЛАМИ

... 1. Фармацевтический состав, содержащий соединение формулы: где R1 является С1-С9алкильной или алкенильной группой с прямой или разветвленной цепью, возможно замещенной С3 -С8циклоалкилом, С3 или С5циклоалкилом, С5-С7циклоалкенилом или Ar1, где указанные алкильная, алкенильная, циклоалкильная или циклоалкенильная группы возможно могут иметь один или более чем один атом водорода, замещенный С1-С4алкилом, С1-С4алкенилом или гидроксилом, и где Ar1 выбран из группы, состоящей из 1-нафтила, 2-нафтила, 2-индолила, 3-индолила, 2-фурила, 3-фурила, 2-тиазолила, 2-тиенила, 3-тиенила, 2-, 3- или 4-пиридила и фенила, имеющих от одного до трех заместителей, которые независимо выбраны из группы, состоящей из водорода, галогена, гидроксила, нитрогруппы, трифторметила, прямого или разветвленного C1-С6алкила или алкенила, С1-С4алкоксила или C1-С4алкенилоксила, феноксигруппы, бензилоксигруппы и аминогруппы; Х является кислородом, серой, метиленом (СН2) или Н2; Y является кислородом или NR2, где R2 является ...

БЕНЗИЛЭФИРАМИНЫ, ПОЛЕЗНЫЕ КАК АНТАГОНИСТЫ CCR-5

... 1. Соединение общей формулы I его энантиомеры, диастереомеры, соли и сольваты, в которой Х представляет собой связь или кислород; m представляет собой 0, 1, 2, 3 или 4; n представляет собой 0, 1 или 2; R1 представляет собой необязательный заместитель, независимо выбираемый в каждом случае из галогена, алкила, галоалкила, нитро или -NR5R6; R2 представляет собой a) водород; или b) алкил, циклоалкил, алкенил, арил или гетероарил, любой из которых может быть, необязательно, замещен группой Y; Y представляет собой a) арил или гетероарил, каждый из которых может быть, необязательно, замещен одним или несколькими Z1, Z2, Z3; b) циклоалкил или гетероцикло, каждый из которых может быть, необязательно, замещен одним или несколькими Z1, Z2, Z3; c) -COOR7; d) -NR8R9; e) CHR10(OR11); f) -C(=O)-NR8R9; g) -NR12-(C=O)-NR8 R9; h) -CN; i) -C(=N-OR13); j) алкокси; R3 и R4 независимо выбирают из a)водорода; b) алкила, циклоалкила, (циклоалкил)алкила, арила, (арил)алкила, гетероцикло, (гетероцикло)алкила, гетероарила ...

ИНГИБИТОРЫ ВИРУСА ГЕПАТИТА С

... 1. Соединение, имеющее формулу где (a) R1 обозначает C1-8 алкил, C3-7 циклоалкил или C4-10 алкилциклоалкил; (b) m обозначает 1 или 2; (c) n обозначает 1 или 2; (d) R2 обозначает Н, C1-6 алкил, C2-6 алкенил или C3-7 циклоалкил, каждый из которых, необязательно, замещен галогеном; (e) R3 обозначает C1-8 алкил, необязательно имеющий следующий заместитель: галоген, циано, амино, C1-6 диалкиламино, C6-10 арил, C7-14 алкиларил, C1-6 алкокси, карбокси, гидрокси, арилокси, C7-14 алкиларилокси, C2-6 алкиловый сложный эфир, C8-15 алкилариловый сложный эфир; C3-12 алкенил, C3-7 циклоалкил или C4-10алкилциклоалкил, где циклоалкил или алкилциклоалкил, необязательно, имеют заместитель: гидрокси, C1-6 алкил, C2-6 алкенил или C1-6 алкокси; или R3, вместе с углеродным атомом, к которому он присоединен, образует C3-7 циклоалкильную группу, необязательно замещенную C2-6 алкенилом; (f) Y обозначает Н, фенил, замещенный нитрогруппой, пиридил, замещенный нитрогруппой или C1-6 алкил, необязательно имеющий в качестве ...

ПРОИЗВОДНЫЕ N-ФОРМИЛГИДРОКСИЛАМИНА В КАЧЕСТВЕ ИНГИБИТОРОВ ПЕПТИДИЛДЕФОРМИЛ АЗЫ (PDF)

... 1. Соединение формулы (I) где X означает -СН2-, -S-, -СН(ОН)-, -CH(OR)-, -CH(SH)-, -CH(SR)-, -CF2-, -C=N(OR)- или -CH(F)-, где R означает алкил, R1 означает арил или гетероарил, каждый R2, R3, R4 и R5 независимо означает водород или алкил, или (R2 или R3) и (R4 или R5) вместе образуют С4-С7циклоалкил, а n равно 0-3, при условии, если n равно О, Х означает –СН2-, или его соль или пролекарство. 2. Соединение по п.1, где Х означает –СН2-, R1 означает гетероарил, R2, R3 и R4 означают водород, R5 означает н-бутил, а n равно 1, или его соль или пролекарство. 3. Соединение по п.1 или 2, где гетероарил означает остаток формулы (II) где каждый R6, R7, R8 и R9 независимо означает водород, алкил, замещенный алкил, гидрокси, алкокси, ацил, ацилокси, SCN, галоген, циано, нитро, тиоалкокси, фенил, гетероалкиларил, алкилсульфонил или формил, или его соль или пролекарство. 4. Соединение по п.1 или 2, где гетероарил означает остаток формулы (III) где каждый R6, R7, R8 и R9 независимо означает водород, алкил ...

ТИАЗОЛИДИН-4-КАРБОНИТРИЛЫ И ИХ АНАЛОГИ, ПРИМЕНЕНИЕ УКАЗАННЫХ СОЕДИНЕНИЙ В КАЧЕСТВЕ ИНГИБИТОРОВ ДИПЕПТИДИЛПЕПТИДАЗ

... 1. Соединение, представленное общей формулой (I), его производные, аналоги, таутомерные формы, стереоизомеры, полиморфы, фармацевтически приемлемые соли, фармацевтически приемлемые сольваты, где Х означает О, S, SO, SO2, NR7 или CHR1; n равно нулю или 1; k равно 1; Z означает О, S и NR7; R1, в двух положениях, независимо выбраны из водорода, либо замещенной или незамещенной группы, выбранной из группы, включающей линейный или разветвленный (C1-C12)алкил, (C2 -C12) алкенил, (С3-С7) циклоалкил, (С5-С7) циклоалкенил, бициклоалкил, бициклоалкенил, гетероциклоалкил, арил, арилокси, аралкил, аралкокси, гетероарил, гетероаралкил, гетероарилокси, гетероаралкокси, где один или несколько гетероатомов независимо выбраны из О, N или S; R2, R3, R4 и R7 независимо выбраны из группы, включающей водород, пергалогеналкил, -(CO)NR8R9, -(CO)R8, -(CO)OR8, -SO2R8, -SOR8, замещенные или незамещенные группы, выбранные из групп, включающих линейный или разветвленный (C1-C12 )алкил, (С2-C12)алкенил, (С3-С7)циклоалкил ...

ПРОИЗВОДНЫЕ ЭНАЛАПРИЛ-НИТРООКСИПРОИЗВОДНЫХ И РОДСТВЕННЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ АСЕ ДЛЯ ЛЕЧЕНИЯ СЕРДЕЧНО-СОСУДИСТЫХ ЗАБОЛЕВАНИЙ

... 1. Соединение общей формулы (I) или его фармацевтически приемлемая соль или стереоизомер: где s имеет значение 1 или 2; А выбран из следующих групп: где n имеет значение от 1 до 6, предпочтительно равен 1 или 2; N0=-COO- или -COOR0, где R0 представляет собой Н или линейный или разветвленный (C1-C10)-алкил; R1 выбран из группы, состоящей из: где N2 имеет те же значения, которые определены для N0, и они могут быть одинаковыми или различными, N2a представляет собой Н, -С(O)-, -COO-, -COOR0, -C(O)R0-, где R0 представляет собой линейный или разветвленный (С1 -С10)-алкил; при условии, что по меньшей мере одна из групп N0, N2 или N2a представляет собой -СОО- или -С(O)-, то есть она имеет свободную валентность, способную к связыванию с X1; 1b) где n является таким, как определено выше, предпочтительно равен 4; N3 представляет собой Н или R2 может представлять собой где N2 представляет собой -COO-, который имеет свободную валентность, способную к связыванию с X1; 1с) где R1c выбран из Н, -СОСН3 ...

ЗАМЕЩЕННЫЕ ПИРРОЛИДИН-2-КАРБОКСАМИДЫ

... 1. Соединение, выбранное из группы, включающейхиральный трет-бутиловый эфир [2-(4-{[(2R,3S,4R,5S)-4-(4-хлор-2-фторфенил)-3-(3-хлор-2-фторфенил)-4-циано-5-(2,2-диметилпропил)-пирролидин-2-карбонил]-амино}-фенил)-этил]-карбаминовой кислоты,рац-трет-бутиловый эфир (4-{[(2R,3S,4R,5S)-4-(4-хлор-2-фторфенил)-3-(3-хлор-2-фторфенил)-4-циано-5-(2,2-диметилпропил)-пирролидин-2-карбонил]-амино}-бензил)-карбаминовой кислоты,этиловый эфир 1-(4-{[(2R,3S,4R,5S)-4-(4-хлор-2-фторфенил)-3-(3-хлор-2-фторфенил)-4-циано-5-(2,2-диметилпропил)-пирролидин-2-карбонил]-амино}-фенил)-пиперидин-4-карбоновой кислоты,1-(4-{[(2R,3S,4R,5S)-4-(4-хлор-2-фторфенил)-3-(3-хлор-2-фторфенил)-4-циано-5-(2,2-диметилпропил)-пирролидин-2-карбонил]-амино}-фенил)-пиперидин-4-карбоновую кислоту,рац-трет-бутиловый эфир 4-{[(2R,3S,4R,5S)-4-(4-хлор-2-фторфенил)-3-(3-хлор-2-фторфенил)-4-циано-5-(2,2-диметилпропил)-пирролидин-2-карбонил]-амино}-4-метилпиперидин-1-карбоновой кислоты,метиловый эфир 4-{[(2R,3S,4R,5S)-4-(4-хлор-2-фторфенил) ...

СПОСОБ ПОЛУЧЕНИЯ СОЕДИНЕНИЙ, ОБЛАДАЮЩИХ АПФ ИНГИБИТОРНОЙ АКТИВНОСТЬЮ

... 1. Способ получения соединений с АПФ ингибирующей активностью, представленных формулой I и их фармацевтически приемлемых солей, где R1-R3 обозначают: R1-H, алкил, фенил; R2-H, алкил; и R3- или или отличающийся тем, что карбоксильную группу аминокислоты формулы II активируют солью урония формулы III в присутствии апротонного растворителя, а затем вводят активированную аминокислоту в реакцию с соответствующим амином из ряда HR3, где R3 или обозначает или 2. Способ по п.1, отличающийся тем, что в качестве аминокислоты формулы II используют N-((S)-1-карбэтоксибутил)-(S)-аланин. 3. Способ по п.1, отличающийся тем, что в качестве аминокислоты формулы II используют 1-((S)-N-(1-(этоксикарбонил)-3-фенилпропил)-L-аланин. 4. Способ по п.1, отличающийся тем, что в качестве амина используют L-пролин. 5. Способ по п.1, отличающийся тем, что в качестве амина используют (2S,3aR, 7aS)-октагидро-1Н-индол-2-карбоновую кислоту или ее эфир. 6. Способ по п.1, отличающийся тем, что в качестве соли урония используют ...

Промоторы гидратообразования углекислого газа на основе амидов аминокислот и этилендиаминтетрауксусной кислоты

Изобретение относится к химии комплексонов, а именно к применению соединений на основе амидов аминокислот и этилендиаминтетрауксусной кислоты общей формулы (I), где R выбран из I-1, I-2, I-3 и I-7, в качестве промоторов гидратообразования углекислого газа. Соединения могут найти применение в улавливании углекислого газа и разделении газов. 2 ил., 1 пр.

СЛОЖНЫЙ α-АЗАРИ-ЛАЛДЕГИДНЫЙ ЭФИР, СПОСОБ ЕГО ПОЛУЧЕНИЯ И ЕГО ПРИМЕНЕНИЯ

Настоящее изобретение относится к сложному α-азари-лалдегидному эфиру, к способу его получения и к его применению. Химическая структура соответствующего сложного α-азари-лалдегидного эфира представлена формулой I. Соответствующее применение представляет собой применение соединения при приготовлении лекарственных средств для успокоения, транквилизации, противодействия сенильной деменции, противодействия судорогам, противодействия эпилепсии и противодействия депрессии. 3 н. и 3 з.п. ф-лы, 4 табл., 12 пр.

ТВЕРДЫЕ ФОРМЫ ФАРМАЦЕВТИЧЕСКИ АКТИВНОГО СОЕДИНЕНИЯ

СОЕДИНЕНИЯ И КОМПОЗИЦИИ В КАЧЕСТВЕ ИНГИБИТОРОВ ПРОТЕАЗЫ, АКТИВИРУЮЩЕЙ КАНАЛЫ

... 1. Соединение формулы (1): ! ! и его фармацевтически приемлемые соли, гидраты, сольваты и стереоизомеры, где !J представляет собой 5-12-членное моноциклическое или конденсированное ! карбоциклическое кольцо, арил, гетероарил или гетероциклическое кольцо, ! содержащее N, О и/или S; ! R1 представляет собой -(CR2)1-NR2, -(CR2)1-NRC(=NR)-NR2, -(CR2)1-C(=NR)-NR2 или 5-7-членное азотсодержащее неароматическое гетероциклическое кольцо; ! W-R2 представляет собой заместитель в любом положении кольца А; ! W представляет собой -O(CR2)k-, -S(CR2)k-, -S(O)(CR2)k-, -SO2(CR2)k- или -OC(O)(CR2)k-; ! R2 представляет собой C1-6 алкил, С2-6 алкенил, С2-6 алкинил, R6, -CR9=CR9-R6 или, где кольцо Е представляет собой необязательно замещенный 5-7-членное моноциклическое или конденсированное карбоциклическое или гетероциклическое кольцо; или W-R2 вместе образуют C1-6 алкил, 5-7-членный арил или -OC(O)NR7R8; ! R3 представляет собой NR7R8 или R6; !R4 и R5 независимо представляют собой Н, C1-6 алкил, ОН или C1-6 ...

НОВЫЕ СОЕДИНЕНИЯ

... 1. Соль вилдаглиптина и фармацевтически приемлемой кислоты в стехиометрическом соотношении 1:1. ! 2. Соль по п.1, являющаяся 4-ацетамидобензоатной, ацетатной, адипатной, альгинатной, 4-аминосалицилатной, аскорбатной, аспартатной, бензолсульфонатной, бензоатной, бутиратной, камфоратной, камфорсульфонатной, карбонатной, циннаматной, цитратной, цикламатной, циклопентанпропионатной, деканоатной, 2,2-дихлорацетатной, диглюконатной, додецилсульфатной, этан-1,2-дисульфонатной, этансульфонатной, формиат. фумаратной, галактаратной, гентизинатной, глюкогептаноатной, глюконатной, глюкуронатной, глутаматной, глицерофосфатной, гликолятной, гемисульфатной, гептаноатной, гексаноатной, гиппуратной, гидрохлоридной, гидробромидной, гидроиодидной, 2-гидроксиэтансульфонатной, изобутиратной, лактатной, лактобионатной, лауратной, малатной, малеатной, малонатной, манделатной, метансульфонатной, нафталин-1,5-дисульфонатной, 2-нафталинсульфонатной, никотинатной, нитратной, октаноатной, олеатной, оротатной, оксалатной ...

1-((3S,4R)-4-(3-ФТОРФЕНИЛ)-1-(2-МЕТОКСИЭТИЛ)ПИРРОЛИДИН-3-ИЛ)-3-(4-МЕТИЛ-3-(2-МЕТИЛПИРИМИДИН-5-ИЛ)-1-ФЕНИЛ-1Н-ПИРАЗОЛ-5-ИЛ)МОЧЕВИНА В КАЧЕСТВЕ ИНГИБИТОРА TRKA КИНАЗЫ

СПОСОБЫ И ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ

... 1. Способ получения бета-амидокарбонильного соединения формулы XXX:включающий следующие стадии:a) взаимодействие соединения формулы XII:с соединением формулы XIII:в присутствии палладиевого катализатора, палладиевого лиганда, основания и растворителя, необязательно включающего катализатор межфазного переноса и необязательно включающего воду, с получением соединения формулы XXXIгде X обозначает уходящую группу;каждый Rобозначает H, необязательно замещенный алкил, необязательно замещенный арил, -CN, -C(O)-О-алкил или галоген;каждый Rнезависимо обозначает необязательно замещенную алифатическую группу, необязательно замещенную гетероциклическую группу или необязательно замещенную арильную группу;каждый Rнезависимо обозначает необязательно замещенный алифатический радикал, необязательно замещенный гетероцикл, необязательно замещенный арил, или Rи Rвместе с группами, к которым они присоединены, образуют необязательно замещенное (5-8)-членное гетероциклическое кольцо; икаждый Rобозначает органический ...

НОВЫЕ ПРОИЗВОДНЫЕ МЕТИЛЦИКЛОГЕКСАНА И ЕГО ПРИМЕНЕНИЕ

... 1. Соединение, выбранное из группы, состоящей из производного метилциклогексана, представленного формулой I ниже, и фармацевтически приемлемых солей, изомера, сольвата и гидрата производного метилциклогексана и их комбинаций:,гдеAr выбран из группы, состоящей из фенила, пиридина и пиридин-N-оксида, каждый из которых замещен одним или более одинаковыми или разными заместителями, выбранными из группы, состоящей из атома водорода, линейного или разветвленного C1-C6алкила, галогена, линейного или разветвленного C1-C6алкокси и трифторметила;X представляет собой O, (C=O)O, NR(C=O)O, NH, (C=O)NH или O (C=O)NH; и Rпредставляет собой H или CH;Y представляет собой CH, O или N-R; Rпредставляет собой H или CH;A представляет собой O или NH;B представляет собой CH или N; иm равен целому числу от 0 до 2, и n равен 0 или 1.2. Соединение по п.1, имеющее одну из следующих структур:3. Фармацевтическая композиция для предупреждения или лечения боли, содержащая:терапевтически эффективное количество производного ...

НОВЫЕ 4-(АЗАЦИКЛОАЛКИЛ)БЕНЗОЛ-1,3-ДИОЛОВЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ ТИРОЗИНАЗ, СПОСОБ ИХ ПОЛУЧЕНИЯ И ИХ ПРИМЕНЕНИЕ В ЛЕЧЕНИИ ЧЕЛОВЕКА И В КОСМЕТИЧЕСКИХ СРЕДСТВАХ

... 1. Соединения общей формулы (I), приведенной ниже:где:R1 представляет собой:- C-C-алкиловый радикал,- C-C-циклоалкиловый радикал,- ариловый радикал,- замещенный ариловый радикал,- аралкиловый радикал,- C-C-алкокси радикал,- аминовый радикал, соответствующий структуре (a):где R2 представляет собой:- водород,- C-C-алкиловый радикал,- C-C-циклоалкиловый радикал,- ариловый радикал,- замещенный ариловый радикал,- пиридиловый радикал,- аралкиловый радикал,- радикал, соответствующий структуре (b):где значение p может представлять собой 1 или 2,- радикал, соответствующий структуре (c)где R4 представляет собой:- карбоксиметиловый, -COOCHили карбоксиэтиловый, -COOEt, радикал,- C-C-алкиловый радикал,- водород,и R5 представляет собой:- замещенный или незамещенный ариловый радикал,- C-C-циклоалкиловый радикал,- пиридил,и R3 представляет собой:- водород,- C-C-алкиловый радикал;или R1 также может представлять собой радикал, соответствующий формуле (d):где R6 представляет собой:- водород,- C-C-алкиловый ...

Полиаминные аналоги в качестве цитотоксических агентов

... 1. Цитотоксический полиаминный аналог, имеющий структуру R1-X-R2, где R1 и R2 - независимо Н или радикал, выбранный из группы, включающей прямой или разветвленный C1-10 алифатический, алициклический, одно- или многокольцевой ароматический, одно- или многокольцевой арил-замещенный алифатический, алифатически замещенный одно- или многокольцевой ароматический, одно- или многокольцевой гетероциклический, одно- или многокольцевой гетероциклически замещенный алифатический и алифатически замещенный ароматический, а также их галогенированные формы; Х - полиамин с двумя концевыми аминогруппами, -(CH2)3-NH- или -СН2-Ph-СН2-, при этом R1 и R2 - не являются одновременно незамещенными бензиловыми радикалами. 2. Аналог по п.1, отличающийся тем, что Х выбирают из группы, содержащей путресцин, спермидин и спермин. 3. Аналог по п.1, отличающийся тем, что Х является путресцином. 4. Аналог по п.3, отличающийся тем, что указанная структура представляет собой соединение, которое выбрано из группы, включающей ...

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

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

АСИММЕТРИЧЕСКИЙ СИНТЕЗ ЗАМЕЩЕННОГО ПИРРОЛИДИН-2-КАРБОКСАМИДА

ФЕНИЛДИФТОРМЕТИЛЗАМЕЩЕННОЕ СОЕДИНЕНИЕ ПРОЛИНАМИДА

ИНГИБИТОРЫ ДИПЕПТИДИЛПЕПТИДАЗЫ IV

... 1. Соединение, выбранное из производных формулы 1, их таутомеров и стереоизомеров и фармацевтически приемлемых солей указанных производных, таутомеров и изомеров где X1 выбирают из атома серы, атома кислорода, сульфинильной группы, сульфонильной группы и метиленовой группы; X2 выбирают из О, S и метилена; X3 обозначает или NR5, или карбонильную, или тиокарбонильную группу; R1 обозначает либо атом водорода, либо нитрильную группу; R2 и R3 выбирают независимо из Н и C1-C6 алкила, или вместе они могут представлять -(СН2)p-; R4 обозначает R4A, когда X3 обозначает NR5, и R4B, когда X3обозначает карбонильную или тиокарбонильную группу; R4A выбирают из R6R7NC(=O), R6R7NC(=S), R8(CH2)qC(=O), R8(CH2)qC(=S), R8(CH2)qSO2, R8(CH2)qOC(=O) и R8(CH2)qOC(=S); R4B обозначает R6R7N; R5 обозначает Н или C1-C6 алкил; R6 и R7 выбирают независимо из R8(CH2 )q или вместе они образуют -(CH2)2-Z1-(CH2)2- или -CHR9-Z2-CH2-CHR10-; R8 выбирают из Н, алкила, циклоалкила, конденсированного с бензольным кольцом, ацила ...

ПЕСТИЦИДНЫЕ КОМПОЗИЦИИ И СВЯЗАННЫЕ С НИМ СПОСОБЫ

СПОСОБ ПОЛУЧЕНИЯ N-АМЕЩЕННЫХ 2-ЦИАНОПИРРОЛИДИНОВ

... 1. Способ получения N-(N'-замещенного глицил)-2-цианопирролидина, включающий по крайней мере (а) реакцию соединения формулы (V) где, независимо друг от друга, X1 и Х3 представляют собой галоген; Х2 представляет собой галоген, ОН, O-С(=O)-СН2Х3, -O-SO2-(С1-8)алкил или -O-SO2-(арил), с L-пролинамидом в присутствии диметилформамида с последующей (б) реакцией полученного соединения без выделения с дегидратирующим агентом, необязательно с последующей (в) реакцией полученного соединения без выделения с соответствующим амином в присутствии основания и (г) выделение полученного соединения в форме свободного основания или кислотной аддитивной соли. 2. Способ по п.1, в котором N-(N'-замещенный глицил)-2-цианопирролидин представляет собой соединение формулы (I) где R представляет собой a) R1R1aN(CH2)m-, в котором R1 представляет собой пиридинильную или пиримидинильную группу, необязательно моно- или независимо дизамещенную (С1-4)алкилом, (C1-4)-алкоксигруппой, галогеном, трифторметилом, циано или ...

ПРОИЗВОДНЫЕ КАПТОПРИЛА

... 1. Соединение общей формулы (I) и/или его фармацевтически приемлемая соль или стереоизомер где Q=-СО-, -ОСО-, -CONH-, -COCH(R)NH-, где R представляет собой Н, линейный или разветвленный (С1-С6)-алкил, -(СН2)2SCH3 или бензил; при условии, что -S- присоединен к -СО; n - целое число, равное 0 или 1; А=Н, W (где W представляет собой C1-С6-алкил, фенил иди бензил) или выбран из следующих групп: 1a) 1б) 1в) где z и Y являются одинаковыми или различными и представляют собой Н или линейный или разветвленный (С1-С4)-алкил; при условии, что когда А выбран из групп 1б и 1в, Q=-СО-; 1г1) 1г2) 1г3) где z и Y определены выше; при условии, что когда А выбран из групп 1г1 -1г3, Q=-COCH(R)NH-, где R определен выше; R3 представляет собой двухвалентный радикал, имеющий следующие значения: а) линейный или разветвленный в любом возможном положении C1-C20 алкилен, необязательно замещенный по крайней мере одним атомом галогена, предпочтительно имеющий от 1 до 5 атомов углерода, или необязательно замещенный циклоалкилен ...

ИНГИБИТОРЫ IAP

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

НОВЫЕ ЦИКЛИЧЕСКИЕ УГЛЕВОДОРОДНЫЕ СОЕДИНЕНИЯ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ

... 1. Соединение общей формулы I ! ! где ! группа представляет циклоалкил, содержащий 4-7 атомов углерода, необязательно замещенный одним или несколькими, одинаковыми или разными заместителями, выбранными из R2, R3, R4 или R5; ! A представляет С1-10 гетероарил, С6-14 арил или C6-10 гетероциклоалкиларил, каждый из которых необязательно замещен одним или несколькими, одинаковыми или разными заместителями, такими как галоген, гидрокси, меркапто, трифторметил, циано, карбокси, -NH2, -C(О)MHZ, нитро, оксо, -S(О)2NH2, C1-4 алкил, C2-4 алкенил, C2-4 алкинил, C1-4 гидроксиалкил, C1-6 галогеналкил, C1-4 алкокси, C1-4 алкоксикарбонил, C1-4 алкилкарбонилокси, C1-4 алкоксикарбонилокси, C1-4 алкоксисульфонилокси, C1-4 алкоксикарбамоил, C1-4 аминокарбонил, C1-4 алкилтио, C3-8 циклоалкил, C3-8 циклоалкенил, C1-6 амино, иминометил, C1-4 аминосульфонил, C1-4 аминокарбонилокси, C1-4 алкилсульфониламино, гидроксииминометил, C1-4 алкилкарбониламино, C1-4 алкилсульфонил, C1-6 гетероциклоалкил, C1-6 гетероциклоалкенил ...

ПРОИЗВОДНОЕ ТРАНС-2-ДЕЦЕНОВОЙ КИСЛОТЫ И СОДЕРЖАЩЕЕ ЕГО ЛЕКАРСТВЕННОЕ СРЕДСТВО

... 1. Производное транс-2-деценовой кислоты, представленное следующей общей формулой (I') или его фармацевтически приемлемая соль:,где X' представляет собой:(a) 1-пирролидил, замещенный карбоксилом или алкоксикарбонилом,(b) 3-тиазолидил,(c) пиперидино, замещенный алкилом, оксо, гидрокси, алкокси, карбоксилом, алкоксикарбонилом, алкиламино, алкиламиноалкилом, фенилом, карбоксиалкилом, алкоксикарбонилалкилом, циано или галогенофенилом,(d) тиоморфолино,(e) 1-пиперазил, который может быть замещен алкилом, карбоксиалкилом, алкоксикарбонилалкилом, алкиламиноалкилом, циклоалкилом, пиперидиноалкилом, фенилалкилом, пиридилом, пиримидилом, карбоксифенилалкилом или алкоксикарбонилфенилалкилом,(f) 1-пиперазил, замещенный фенилом, который может быть замещен алкиламино, галогеном, алкокси, алкилом, гидрокси, карбоксиалкокси или алкоксикарбонилалкокси,(g) 1,4-диазепанил, который может быть замещен алкилом или алкиламиноалкилом, или(h) карбоксиморфолино.2. Производное транс-2-деценовой кислоты или его фармацевтически ...

Способ получения галоидзамещенных меркаптоациламинокислот

Способ получения производныхпРОлиНА

Способ получения производных плевромутилина или их гидрохлоридов

Изобретение относится к полициклическим соединениям, в частности к получению производных плевромутилина ф-лы @ где R 1-C 1-C 6-аминоалкил, или их гидрохлоридов, которые проявляют антимикробную активность. Цель - получение более активных соединений. Получение ведут реакцией соответствующего замещенного амина со сложным эфиром соединения ф-лы HOOCR 2, где R 2-C 1-C 6-алкиламин, аминогруппа которого содержит защитные группы (такую как C(O)OC(CH 3/ 3) при комнатной температуре, после удаления защитных групп целевой продукт выделяют в виде основания или его гидрохлорида. 2 табл.

Способ получения 1-(3-бром/2S/метилпропионил/-пирролидин-(2S)-карбоновой кислоты

Изобретение касается гетероциклических веществ, в частности получения 1- З-бром-(25)-метилпропионил - пирролидин-(28)-карбоновой кислоты - полупродукта для синтеза меркаптоацил- пролинов, обладающих фармакологической активностью. Цель - повьшение выхода целевого продукта. Последний получают реакцией L-пролина с триметил- силилхлоридом в среде Ш1ертного органического растворителя (CHj,Cl; 1,2- дихлорэтан, СНС1,, бензол, толуол) в присутствии органического основания (триэтиламин или пиридин) или неорганического основания ( или ), Эти условия обеспечивают выход (до 78,8%) целевого продукта, содержащего до 0,5% мётакроилпролина, с т.пл. 64-69 с. 2 з.п. ф-лы.

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

NEUARTIGE ANTIKOAGULIERENDE PEPTIDDERIVATE UND ARZNEIMITTEL DIE SOLCHE ENTHALTEN SO WIE ENTSPRECHENDES HERSTELLUNGSVERFAHREN

3-(3,4-DIOXYPHENYL)-PYRROLIDINE ALS INHIBITONEN DER TYP IV - PHOSPHODIESTERASE ZUR BEHANDLUNG VON ENTZÜNDUNGSKRANKHEITEN

SUBSTITUIERTE PYRROLIDINE ALS INHIBITOREN DER ZELLADHÄSION

DIPEPTIDYLPEPTIDASE-HEMMER ZUR BEHANDLUNG VON DIABETES

Verfahren zur Herstellung von neuen N-substituierten 5-Cyan-pyrrolidin- und 6-Cyan-piperidin-verbindungen

HEPATITIS-C-VIRUS-HEMMER

AZAHETEROZYKLISCHEDERIVATE ZUR BEHANDLUNG VON HAARAUSFALL UND NEUROLOGISCHER KRANKHEITEN

Perylenquinon (UCN-1028D)-Derivate.

Verfahren zur Herstellung von 10-[Polyalkylpyrrolidyl-(3')-methyl]-phenthiazinen

1,2-Ethandiolderivate und ihre Salze, Verfahren zu ihrer Herstellung und sie enthaltende gehirnfunktionsverbessernde Mittel.

1,2-Ethandiolderivate und ihre Salze, Verfahren zu ihrer Herstellung und sie enthaltende gehirnfunktionsverbessernde Mittel

1,2,3,4-Tetrahydronaphthylaminderivate mit nootroper Aktivität und diese enthaltenden Arzneimittel.

Hydantoinverbindungen

BIPHENYLAMIDIN-DERIVATE

CYCLISCHE ACETALE DES GLUTAMINSAEURE- (GAMMA)-SEMIALDEHYDS, VERFAHREN ZU DEREN HERSTELLUNG UND IHRE VERWENDUNG

VERFAHREN ZUR HERSTELLUNG VON MONO-, BI- UND TRICYCLISCHEN AMINOSAEUREN

ALKANOYLPROLIN-DERIVATE UND DEREN HOMOLOGEN, IHRE HERSTELLUNG UND VERWENDUNG

SUBSTITUIERTE HETEROCYCLISCHE VERBINDUNGEN UND DEREN VERWENDUNG ZUR BEHANDLUNG MULTIPLER MEDIKAMENTENRESISTENZ

MOLEKÜLMODELL FÜR VLA-4-INHIBITOREN

Verfahren zur Herstellung von cis- und trans-1,4-Dialkyl-L-und -D-prolinen

METHOD OF ACYLATION

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

ACYLOXYKETONE SUBSTITUTED IMINO AND AMINO ACIDS

FLUORINATION OF ORGANIC COMPOUNDS

... 1353519 Fluorination of organic compounds MERCK & CO Inc 26 July 1971 [3 Aug 1970 18 June 1971] 34887/71 Heading C2C [Also in Division C3] Substitutive fluorination of an organic compound containing at least one replaceable hydrogen atom attached to a carbon atom is effected by contacting the organic compound in the liquid or solid state with a C 1-5 fluoroxyperfluoroalkane or fluoroxypentafluorosulphur in the presence of a free-radical initiator, e.g. light, ionizing radiation or a chemical chain initiator, such as an azo compound, e.g. azo-bis-isobutyronitrile. The substrate is preferably dissolved in a solvent inert to the fluorination reaction, e.g. fluorotrichloromethane or similar halogenated alkane or a strong acid such as liquid HF, fluorosulphonic acid, trifluoroacetic acid or sulphuric acid. Substrates include mono- or polynuclear aromatic or alicyclic compounds, alkanes, alkenes, amino acids, fatty acids or their amides and heterocyclic compounds. Many specific examples are given ...

Process and intermediates for preparing 4-substituted prolines using triphenyl cerium

A compound (for preparing an ACE inhibitor), namely, triphenyl cerium and a process for preparing same by reacting cerium trichloride (CeCl3) with phenyllithium, are provided.

Substituted saturated aza heterocycle inhibitors of nitric oxide synthase

Compounds of Formula (I) wherein the symbols are as defined in the specification, most of which are novel compounds, and pharmaceutically acceptable salts thereof, are useful in the treatment of nitric oxide synthase mediated diseases and disorders.

A pharmaceutical product comprising a salicylate of an esterifiable ace-inhibitor

Salicylates of esterifiable ACE inhibitors, especially Captropril-S-aspirinate, and processes for their preparation are described.

PROCESS FOR PRODUCING PYRROLIDINE DERIVATIVES

The present invention relates to a novel process for preparing pyrrolidine derivatives of the formula (i): characterized in that the compound of the following formula (II): (wherein X is bromo or chloro) is reacted with the compound of the following formula: Cl-CO-R' (wherein R' is methoxy, ethoxy or t-butoxy) to obtain the acid anhydride of the following formula (III): and the compound of formula (III) is acylated with the compound of the following formula (IV): to obtain the compound of the following formula (V): and the compound of formula (V) is reacted with thiourea to obtain the compound of the following formula (VI): which is claimed per se, and, finally, the compound of formula (VI) is hydrolyzed to obtain the pyrrolidine derivatives of the formula (I).

MERCAPTOACYL DERIVATIVES OF PROLINES AND PROLINES

Cyclodextrin clathrate compounds of sulfur-containing compounds

PCT No. PCT/JP82/00050 Sec. 371 Date Sep. 30, 1982 Sec. 102(e) Date Sep. 30, 1982 PCT Filed Feb. 24, 1982 PCT Pub. No. WO82/02890 PCT Pub. Date Sep. 2, 1982.This invention relates to inclusion compounds of cyclodextrin with the compounds of the general formula ?I! and salts thereof, which show pharmacological effects (for example antihypertensive effect), ?I! wherein A is straight or branched lower alkylene; R1 is hydrogen or lower alkyl; R2 is hydrogen, lower alkyl, phenyl, phenyl-lower alkyl, hydroxyphenyl-lower alkyl, hydroxy-lower alkyl, amino-lower alkyl, guanidino-lower alkyl, imidazolyl-lower alkyl, indolyl-lower alkyl, mercapto-lower alkyl or lower alkylthio-lower alkyl; R1 or R2 may join to complete pyrrolidine ring or thiazolidine ring, and each ring may be substituted by phenyl or pyridyl, and phenyl may be resubstituted by hydroxy, lower alkoxy, halogen, nitro or sulfamoyl; R3 is hydrogen or said lower alkyl and lower alkoxy having 1 to 6 carbon atoms.

(1,4) Thiazines or thiazepines

Compounds having the formula wherein R is hydrogen or alkyl, n is 0 or 1 and m is 1 or 2 have hypotensive activity. Those compounds of the above formula wherein n is 1 are useful intermediates for the preparation of other hypotensive agents having the formula ...

BENZOIC ACID DERIVATIVES

Organic compounds

Tetrapeptide analogs

AMINOALKYLBENZENE DERIVATIVES

Acyloxyketone substituted imino and amino acids

Acyloxyketone substituted imino and amino acids of the formula are disclosed. These compounds are useful hypotensive agents due to their angiotensin converting enzyme inhibition activity.

BICYLO(2.2.2)OCTANE DERIVATIVES

PHENOL DERIVATIVES

BENZOIC ACID DERIVATIVES

Organic compounds

Small molecule inhibitors of rotamase enzyme activity

Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme

The present invention relates to compounds which are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, and other diseases and conditions that are mediated by excessive glucocorticoid action.

11-Beta-Hydroxysteroid Dehydrogenase Type 1 Active Compounds

The use of substituted amides for modulating the activity of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and the use of these compounds as pharmaceutical compositions, are described. Also a novel class of substituted amides, of the general formula I. Their use in therapy, pharmaceutical compositions comprising the compounds, as well as their use in the manufacture of medicaments are described. The present compounds are modulators and more specifically inhibitors of the activity of 11βHSDI and may be useful in the treatment of a range of medical disorders where a decreased intracellular concentration of active glucocorticoid is desirable.

Novel method for producing optically active pyrrolidine compound

[Object] A novel method for producing an optically active pyrrolidine compound, which is useful as a production intermediate of a pharmaceutical, and a production intermediate thereof, is provided. [Means for Solution] According to the production method of the present invention, a chloro compound that is a key intermediate can be produced efficiently industrially by subjecting a mixture of regioisomers obtained by reacting an optically active epoxy compound substituted with aryl, which is easily available, with an amine compound, to chlorination. Furthermore, an optically active pyrrolidine compound can be produced industrially efficiently with the key intermediate. [Selected Figure] None

Dihydrolipoic Acid Derivatives Comprising Nitric Oxide and Therapeutic Uses Thereof

Compounds are provided that comprise dinitroso-derivatives of dihydrolipoic acid. Pharmaceutical compositions comprising the compounds and methods of using the compounds for treating various diseases and disorders, including angina, hypertension, diabetes, dyslipidemia, renal insufficiency, myocardial infarction, stroke, atherosclerosis, and the target organ damage that accompanies these various diseases and disorders, are further provided. The compounds are useful in improving vasodilation, reducing low-density lipoprotein oxidation, and reducing inflammation in a subject.

Compounds act at multiple prostaglandin receptors giving a general anti-inflammatory response

The present invention provides compounds, that are N-alkyl-2-(1-(5-substituted-2-(3-oxo-3-(trifluoromethylsulfonamido)propyl)benzyl)pyrrolidin-2-yl)oxazole-4-carboxamide wherein the 5 substituent is selected from the group consisting of halo and alkyloxy radicals. The compound may be represented by the following formula wherein R 1 is selected from the group consisting of CO 2 R 7 and CON(R 7 )SO 2 R 7 wherein R 1 , R 2 , R 3 , R 4 , and R 7 are as defined in the specification. The compounds may be administered to treat DP 1 , FP, EP 1 , EP 3 , TP and/or EP 4 receptor mediated diseases or conditions.

Substituted carbamoylcycloalkyl acetic acid derivatives as nep

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

Pyrrolidine Compounds Which Modulate The CB2 Receptor

Compounds which modulate the CB2 receptor are disclosed. Compounds according to the invention bind to and are agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain. (I)

IAP BIR domain binding compounds

Disclosed herein is an isomer, enantiomer, diastereoisomer or tautomer of a compound represented by Formula I: or a prodrug, or a pharmaceutically acceptable salt, or labeled with a detectable label or an affinity tag thereof; wherein R 1 , R 1a , R 100 , R 100a , R 2 , R 200 , W, B, and W 1 are defined herein. Also disclosed are methods of using compounds of Formula I to treat proliferative disorders such as cancer.

Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as alzheimer's disease, type 2 diabetes and parkinson's disease

Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.

Process for preparing alpha-carboxamide derivatives

The present application provides a process for the preparation of α-carboxamide pyrrolidine derivatives of formula (I), wherein R 1 and R 2 are independently hydrogen, C 1-6 alkyl or C 3-6 cycloalkylC 1-6 alkyl; or such R 1 and R 2 , together with the nitrogen to which they are attached, may form an unsubstituted 3-, 4-, 5- or 6-membered saturated ring; X is carbon or nitrogen; n is 0, 1 or 2, wherein when present each R 5 is independently selected from the list consisting of C 1-3 alkyl, halogen, cyano, haloC 1-3 alkyl, hydroxy, C 1-3 alkoxy and C 1-3 haloalkoxy; either R 6 or R 7 is —O—R 8 , —OCHR 9 R 8 ,—NCH 2 R 8 or —(CH 2 ) 2 R 8 wherein the other R 6 or R 7 is hydrogen or R 5 ; and wherein R 8 is a phenyl ring or wherein the phenyl ring is optionally substituted by one or more groups independently selected from the list consisting of C 1-3 alkyl, halogen, cyano, haloC 1-3 alkyl, hydroxy, C 1-3 alkoxy and C 1-3 haloalkoxy; and R 9 is hydrogen or C 1-3 alkyl.

Process of making alpha-aminooxyketone/alpha-aminooxyaldehyde and alpha-hydroxyketone/alpha-hydroxyaldehyde compounds and a process making reaction products from cyclic alpha, beta-unsaturated ketone substrates and nitroso substrates

The present invention is directed to a process of making α-aminooxyketone and α-hydroxyketone compounds. The synthetic pathway generally involves reacting an aldehyde or ketone substrate and a nitroso substrate in the presence of a catalyst of the formula (IV): wherein X a -X c represent independently nitrogen, carbon, oxygen or sulfur and Z represents a 4 to 10-membered ring with or without a substituent and optionally a further step to convert the α-aminooxyketone compound formed to the α-hydroxyketone compound. The present invention results in α-aminooxyketone and α-hydroxyketone compounds with high enantioselectivity and high purity. The present invention is also directed to a catalytic asymmetric O-nitroso Aldol/Michael reaction. The substrates of this reaction are generally cyclic α,β-unsaturated ketone substrate and a nitroso substrate. This methodology generally involves reacting the cyclic α,β-unsaturated ketone substrate and the nitroso substrate in the presence of a proline-based catalyst, to provide a heterocyclic product.

Development of Novel Detergents for Use in PCR Systems

This disclosure relates to novel detergents for use in various procedures including, for example, nucleic acid amplification reactions such as polymerase chain reaction (PCR). Methods for preparing the modified detergents are also described.

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

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

SUBSTITUTED BIARYL ALKYL AMIDES

Disclosed herein are substituted biaryl alkyl amide compounds, methods of synthesizing substituted biaryl alkyl amide compounds and methods of treating diseases and/or conditions with substituted biaryl alkyl amide compounds. 2. The compound of claim 1 , wherein n is selected from the group consisting of 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , and 5.3. The compound of claim 2 , wherein n is 2.4. The compound of claim 1 , wherein each Ris halo.5. The compound of claim 4 , wherein each Ris chloro.6. The compound of claim 1 , wherein Z claim 1 , Z claim 1 , Zand Zare each —CH—.7. The compound of claim 1 , wherein Ris (Calkoxy)Calkyl.8. The compound of claim 7 , wherein Ris methoxymethyl or ethoxymethyl.9. The compound of claim 1 , wherein Ris (aryloxy)Calkyl.10. The compound of claim 9 , wherein Ris phenoxymethyl.11. The compound of claim 1 , wherein Ris Cheterocyclyl.12. The compound of claim 11 , wherein Ris selected from optionally substituted tetrahydrofuranyl or optionally substituted pyrrolidinyl.13. The compound of claim 12 , wherein the nitrogen atom in pyrrolidinyl is protected with a t-butyloxycarbonyl (Boc) protecting group.14. The compound of claim 1 , wherein Ris Ccycloalkyl.15. The compound of claim 14 , wherein Ris cyclopentyl.16. The compound of claim 1 , wherein Ris haloalkyl.17. The compound of claim 16 , wherein Ris selected from the group consisting of —CHCl claim 16 , —CHBr claim 16 , —CHCHCl claim 16 , —CHCHBr claim 16 , —CH(Cl)CHand —CH(Br)CH.18. The compound of claim 1 , wherein Ris optionally substituted aminoalkyl.19. The compound of claim 18 , wherein Ris selected from the group consisting of —CHNH claim 18 , —CHNH(Boc) claim 18 , —CH(NH)CH claim 18 , and —CH(Boc-NH)CH.20. The compound of claim 1 , wherein Ris —OH.22. The compound of claim 21 , wherein Ris —OH.23. The compound of claim 1 , wherein Ris selected from the group consisting of —OH claim 1 , —NHR claim 1 , an optionally substituted Calkoxy claim 1 , and an optionally ...

C7-Fluoro Substituted Tetracycline Compounds

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

HETERO-SUBSTITUTED ACETANILIDE DERIVATIVES AS ANALGESIC AGENTS

Hetero-substituted acetanilide derivatives are disclosed as analgesic agents. The compounds of the invention are useful in methods for treating a disease or condition in a mammal characterized by pain and/or fever. 123-. (canceled)251. A compound of claim wherein Rand Rtaken together form an optionally substituted imidazole and enantiomers , diastereomers , tautomers , or pharmaceutically acceptable salts thereof.26. A compound selected from the group consisting of:pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide;5-Methyl-1H-pyrazole-3-carboxylic acid (4-hydroxy-phenyl)-amide; and3H-Imidazole-4-carboxylic acid (4-hydroxy-phenyl)-amide;and enantiomers, diastereomers, tautomers, or pharmaceutically acceptable salts thereof.27. A compound of claim 26 , wherein the compound is pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide and enantiomers claim 26 , diastereomers claim 26 , tautomers claim 26 , or pharmaceutically acceptable salts thereof.28. A compound of claim 26 , wherein the compound is 5-Methyl-1H-pyrazole-3-carboxylic acid (4-hydroxy-phenyl)-amide and enantiomers claim 26 , diastereomers claim 26 , tautomers claim 26 , or pharmaceutically acceptable salts thereof.30. A composition of claim 29 , wherein Rand Rtaken together form an optionally substituted imidazole and enantiomers claim 29 , diastereomers claim 29 , tautomers claim 29 , or pharmaceutically acceptable salts thereof.31. A composition comprising a compound selected from the group consisting of:pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide;5-Methyl-1H-pyrazole-3-carboxylic acid (4-hydroxy-phenyl)-amide; and3H-Imidazole-4-carboxylic acid (4-hydroxy-phenyl)-amide;and enantiomers, diastereomers, tautomers, or pharmaceutically acceptable salts thereof.32. The composition of wherein the compound is pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide and enantiomers claim 31 , diastereomers claim 31 , tautomers claim 31 , or pharmaceutically acceptable salts thereof.33. The composition of ...

NOVEL PYRROLIDINE DERIVATIVES

The invention relates to a compound of formula (I) 2. The compound according to claim 1 , wherein Ris halophenylcycloalkyl or halopyridinylcycloalkyl.3. The compound according to claim 1 , wherein Ris selected from the group consisting of chlorophenylcyclopropyl claim 1 , chlorofluorophenylcyclopropyl claim 1 , bromophenylcyclopropyl claim 1 , bromofluorophenylcyclopropyl and chlorofluoropyridinylcyclopropyl.4. The compound according to claim 1 , wherein Rand Rare independently selected from hydrogen and alkyl.5. The compound according to claim 1 , wherein Rand Rare independently selected from the group consisting of hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl and butyl.6. The compound according to claim 1 , wherein R claim 1 , Rand Rare independently selected from the group consisting of halogen claim 1 , haloalkyl and haloalkoxy.7. The compound according to claim 1 , wherein R claim 1 , Rand Rare independently selected from the group consisting of hydrogen claim 1 , chloro claim 1 , trifluoromethyl and trifluoroethoxy.8. The compound according to claim 1 , wherein Ris chloro or trifluoromethyl.9. The compound according to claim 1 , wherein Ris hydrogen.10. The compound according to claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , chloro and trifluoroethoxy.11. The compound according to claim 1 , wherein one of Rand Ris hydrogen and the other one is alkyl or cycloalkyl.12. The compound according to claim 1 , wherein one of Rand Ris hydrogen and the other one is selected from the group consisting of ethyl claim 1 , propyl claim 1 , butyl and cyclopropyl.13. The compound according to selected from the group consisting of(2S,4R)-tert-butyl 2-((S)-1-(cyclopropylamino)-1,2-dioxopentan-3-ylcarbamoyl)-4-(2,4-dimethylphenylsulfonyl)pyrrolidine-1-carboxylate;(2S,4R)-tert-butyl 4-(4-chloro-2-methylphenylsulfonyl)-2-(S)-1-(cyclopropylamino)-1,2-dioxopentan-3-ylcarbamoyl)pyrrolidine-1-carboxylate;(2S,4R)—N—((S)-1-(cyclopropylamino)- ...

4-carboxybenzylamino derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

NOVEL COMPOUNDS AS DPP-IV INHIBITORS AND PROCESS FOR PREPARATION THEREOF

The present invention relates to process for preparation of novel compounds which are acting as inhibitors of dipeptidyl peptidase-IV enzyme and is depicted by the structural formula as given below: Formula VI. Which are useful in the treatment or prevention of diseases in which the dipeptidylpeptidase-IV enzyme is involved, such as diabetes and particularly type-2 diabetes. 5. The process as claimed in claim 3 , wherein Peptide bond is formed by coupling between a carboxyl group and an amino group in presence of coupling agents.6. The coupling agents as claimed in are selected from DCC claim 5 , EDC claim 5 , DIC and like.7. The process as claimed in claim 3 , the saponification reaction is carried out by using Inorganic base.8. The process as claimed in claim 7 , wherein the inorganic base is selected from NaOH claim 7 , KOH claim 7 , LiOH and like claim 7 , preferably NaOH and LiOH.1519-. (canceled)21. The process as claimed in claim 4 , wherein Peptide bond is formed by coupling between a carboxyl group and an amino group in presence of coupling agents.22. The coupling agents as claimed in are selected from DCC claim 21 , EDC claim 21 , DIC and like.23. The process as claimed in claim 4 , the saponification reaction is carried out by using Inorganic base.24. The process as claimed in claim 23 , wherein the inorganic base is selected from NaOH claim 23 , KOH claim 23 , LiOH and like claim 23 , preferably NaOH and LiOH. The present invention relates to process for preparation of novel compounds which are acting as inhibitors of dipeptidyl peptidase-IV enzyme and are useful in the treatment or prevention of diseases in which the dipeptidylpeptidase-IV enzyme is involved, such as diabetes, particularly type-2 diabetes.Various amino peptidases are present in the mammals and catalyze the sequential release of peptides from polypeptides such as pyroglutamyl aminopeptidase and prolyaminpeptidase in addition to dipeptidyl peptidase. Dipeptidyl peptidase family includes ...

Glutamate receptor modulators and therapeutic agents

The present invention discloses methods of modulating the activity of Group I mGluRs using a defined class of benzamide compounds. In one embodiment, methods of modulating the activity of mGluR1 are provided. In another embodiment, methods of modulating the activity of mGluR5 are provided. In still another embodiment, methods of simultaneously modulating the activities of both mGluR1 and mGluR5 are provided. The present invention also provides methods of treating diseases or disorders which are mediated in full or in part by Group I mGluRs using one or more compounds belonging to the defined class of benzamide compounds. The present invention further provides methods of preventing diseases or disorders which are mediated in full or in part by Group I mGluRs using one or more compounds belonging to the defined class of compounds. 3. The method of wherein the disease or disorder is selected from the group consisting of cerebral deficits subsequent to cardiac bypass surgery and grafting claim 1 , cerebral ischemia claim 1 , stroke claim 1 , cardiac arrest claim 1 , spinal cord trauma claim 1 , head trauma claim 1 , perinatal hypoxia claim 1 , hypoglycemic neuronal damage claim 1 , AIDS-induced dementia claim 1 , ocular damage claim 1 , retinopathy claim 1 , muscular spasms claim 1 , convulsions claim 1 , migraine headaches claim 1 , urinary incontinence claim 1 , drug tolerance claim 1 , drug withdrawal claim 1 , drug cessation claim 1 , smoking cessation claim 1 , panic attack claim 1 , emesis claim 1 , brain edema claim 1 , neuropathic pain claim 1 , nociceptive pain claim 1 , Tourette's syndrome claim 1 , attention deficit disorder claim 1 , motor disorders claim 1 , tardive dyskinesia claim 1 , eating disorders claim 1 , sexual disorders claim 1 , obesity claim 1 , convulsive disorders claim 1 , circadian disorders claim 1 , neurodegenerative diseases claim 1 , amyelotrophic lateral sclerosis claim 1 , Parkinson's disease claim 1 , and multiple sclerosis claim 1 , ...

CONJUGATES OF POLYUNSATURATED FATTY ACIDS AND AMINE-CONTAINING COMPOUNDS AND USES THEREOF

Novel chemical conjugates derived from unsaturated fatty acids and therapeutically active agents, are disclosed. The chemical conjugates are designed and characterized as COX-2 and/or 5-LOX inhibitors and are useful in the treatment of inflammatory diseases and disorders such as Alzheimer's disease, Parkinson's disease, asthma, osteoarthritis, rheumatoid arthritis, pain, primary dysmenorrhea, Crohn's disease and ulcerative colitis. 140-. (canceled)41. A method for treating dermatitis in a subject in need comprising the step of administering the subject in need docosa-4 ,7 ,10 ,13 ,16 ,19-hexaenoic acid linked to a hydroxyproline , thereby treating dermatitis in the subject.42. A method of synthesizing 1-docosa-4 ,7 ,10 ,13 ,16 ,19-hexaenoyl-4-hydroxy-pyrrolidine-2-carboxylic acid comprising:mixing tetrahydrofurane with decosahexanoic acid;adding triethylcloroformate;adding triethylamine;stirring and filtering;adding a solution of hydroxyproline and NaOH in water;adding strong acid;adding hexane;collecting organic layer; and drying43. The method according to claim 42 , wherein the step of stirring following the addition of the hydroxyproline and NaOH in water solution claim 42 , is for at 12 hours.44. The method according to claim 42 , wherein the step of drying is over anhydrous sulfate.45. A chemical conjugate comprising a first moiety and a second moiety covalently linked therebetween claim 42 , wherein said second moiety is derived from docosa-4 claim 42 ,7 claim 42 ,10 claim 42 ,13 claim 42 ,16 claim 42 ,19-hexaenoic acid claim 42 , and wherein said first moiety is derived from a therapeutically active agent or a derivative thereof claim 42 , each independently having a functional group for forming a covalent bond with said second moiety claim 42 , with the proviso that said first moiety is not hydroxyproline claim 42 , the chemical conjugate being a cyclooxygenase-2 (COX-2) inhibitor.46. The chemical conjugate of claim 45 , being further a 5-lipoxygenase (5-LOX ...

HEXAFLUOROISOPROPYL CARBAMATE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION

The disclosure relates to hexafluoroisopropyl carbamate derivatives of general formula (I): 2. The compound of formula (I) according to claim 1 , wherein:{'sup': '1', 'Rrepresents a phenyl, naphthyl, indanyl, benzoxazole, benzisoxazole, benzimidazole, benzotriazole, oxadiazole, indazole, isoxazole, pyridine, pyrazine, pyrimidine, thienyl, thiazole, benzothiophene, indole, dihydrobenzodioxane, benzothiadiazole, pyrazole, dihydrobenzoxazine or indoline group;'}{'sup': '2', 'sub': 3', '3', '2', '2', '2', '2', '2, 'Rrepresents one or more groups chosen from a halogen atom or a methyl, trifluoromethyl, methoxy, trifluoromethoxy, cyano, oxo, CHNHCO, CHSO, NHCO, NHSOand pyrrolidine-SOgroup;'}{'sup': '3', 'Rrepresents a group chosen from a phenyl and an oxazole; and also the compound 2,2,2-trifluoro-1-(trifluoromethyl)ethyl 4-{[3-(2-methylpyrimidin-4-yl)benzenesulphonylamino]methyl}piperidine-1-carboxylate,'}in the form of the base or of an addition salt with an acid.3. The compound of formula (I) according to claim 1 , wherein:{'sub': 2', '2', '2', '2', '3', '2, 'Z represents a bond or a CH, (CH), CH═CH, C≡C, OCHor OC(CH)group,'}in the form of the base or of an addition salt with an acid.4. The compound of formula (I) according to claim 1 , wherein:{'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '3', '2, 'A represents a bond, an oxygen atom, a sulphur atom, an OCHgroup, an O—(CH)group, an NH, NHCHor NH(CH)group, an SOor CO group, a CONH group, a CONHCHor CONH(CH)group, an SONH group, an SONHCHor SONH(CH)group, an SONHCO, SONHCONH or SONHCONHCHgroup, an OCONH group, an NHCONH group, an NHCONHCHgroup, an N(CH)CONHCH, NHCONH(CH)or N(CH)CONH(CH)group or an SON(CH)CHgroup,'}in the form of the base or of an addition salt with an acid.5. The compound of formula (I) according claim 1 , wherein m and n represent 1 claim 1 , in the form of the base or of an addition salt with an ...

CHIRAL AUXILIARIES

Chiral auxiliaries useful for efficiently producing a phosphorus atom-modified nucleic acid derivative with high stereoregularity, and compounds represented by the following the general formula (I) or the general formula (XI) for introducing the chiral auxiliaries. 2. The compound or a salt thereof according to claim 1 , wherein Rand Rare hydrogen atom or an alkyl group claim 1 , Ris phenyl group claim 1 , Rand Rare hydrogen atom or an alkyl group claim 1 , and Y is —C(R)(R)— (Rand Rare independently hydrogen atom or an alkyl group claim 1 , and when Rrepresents an alkyl group claim 1 , Rmay bind with the phenyl group represented by Rto form a ring) claim 1 , o-phenylene group claim 1 , or naphthalene-1 claim 1 ,2-diyl group.8. The method according to claim 7 , wherein 3% dichloroacetic acid (DCA) in dichloromethane is used for the acidic condition in the step (c).9. The method according to claim 7 , wherein claim 7 , as the modification of phosphorus atom claim 7 , a group represented by X (X represents an alkylthio group which may have a substituent claim 7 , an alkenylthio group which may have a substituent claim 7 , an alkynylthio group which may have a substituent claim 7 , an arylthio group which may have a substituent claim 7 , thiol group claim 7 , an alkoxy group which may have a substituent claim 7 , —BH claim 7 , —Se claim 7 , an alkyl group which may have a substituent claim 7 , an alkenyl group which may have a substituent claim 7 , an alkynyl group which may have a substituent claim 7 , an aryl group which may have a substituent claim 7 , an acyl group which may have a substituent claim 7 , or —N(R)(R) (Rand Rindependently represent hydrogen atom claim 7 , an alkyl group which may have a substituent claim 7 , an alkenyl group which may have a substituent claim 7 , an alkynyl group which may have a substituent claim 7 , or an aryl group which may have a substituent) is introduced on the phosphorus atom.11. The compound or a salt thereof according to ...

NOVEL DIPEPTIDYL-PEPTIDASE-IV INHIBITORS

The invention comprises novel inhibitors of dipeptidyl peptidase IV (DPP-IV) with beta blocker activity, pharmaceutical compositions comprising therapeutically effective amounts of novel inhibitors of DPP-IV, and novel methods of treating medical conditions are provided. The novel inhibitors of DPP-IV described herein are useful in the treatment of neurological disorders, diabetes, inflammatory disorders such as arthritis, obesity, osteoporosis, hypertension, and glaucoma of such other enumerated conditions as can be treated with inhibitors of DPP-IV and beta blockers. 2. A dipeptidyl peptidase IV inhibiting compound of formula I according to in combination with a pharmaceutically acceptable carrier claim 1 , diluent claim 1 , or excipient.4. A dipeptidyl peptidase IV inhibiting compound of formula II according to in combination with a pharmaceutically acceptable carrier claim 3 , diluent claim 3 , or excipient.6. A dipeptidyl peptidase IV inhibiting compound of formula IIa according to in combination with a pharmaceutically acceptable carrier claim 5 , diluent claim 5 , or excipient.9. The method for treating a medical condition according to claim 8 , wherein said dipeptidyl peptidase IV inhibiting compound or pharmaceutically acceptable salt thereof is a beta blocking agent.10. The method for treating a medical condition according to claim 8 , wherein said dipeptidyl peptidase IV inhibiting compound or pharmaceutically acceptable salt thereof is an immunosuppressive agent effective against autoimmune disease.11. The method for treating a medical condition according to claim 8 , wherein said dipeptidyl peptidase IV inhibiting compound or pharmaceutically acceptable salt thereof is an anti-inflammatory agent effective against inflammatory disorders.12. The method for treating a medical condition according to claim 8 , wherein said dipeptidyl peptidase IV inhibiting compound or pharmaceutically acceptable salt thereof is a metabolic agent effective against metabolic ...

CYTOKINE INHIBITORS

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

MODIFIED LYSINE-MIMETIC COMPOUNDS

Lysine mimetic compounds having useful pharmacological activity such as antiarrhythmic activity and desirable bioavailability properties are disclosed. 2. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , ester claim 1 , hydrate claim 1 , or prodrug thereof claim 1 , wherein k is 0 or 1.3. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , ester claim 1 , hydrate claim 1 , or prodrug thereof claim 1 , wherein:{'sup': 2', '3, 'Y′ is NRR;'}{'sup': '2', 'Ris H; and'}{'sup': 3', '6', '6, 'sub': '1-10', 'Ris selected from the group consisting of H, an optionally substituted Calkyl, C(O)R, and C(O)OR.'}4. The compound according to claim 3 , or a pharmaceutically acceptable salt claim 3 , ester claim 3 , hydrate claim 3 , or prodrug thereof claim 3 , wherein Ris H.5. The compound according to claim 3 , or a pharmaceutically acceptable salt claim 3 , ester claim 3 , hydrate claim 3 , or prodrug thereof claim 3 , wherein Ris C(O)Rand Ris H or an optionally substituted Calkyl.6. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , ester claim 1 , hydrate claim 1 , or prodrug thereof claim 1 , wherein Y′ is OR.7. The compound according to claim 6 , or a pharmaceutically acceptable salt claim 6 , ester claim 6 , hydrate claim 6 , or prodrug thereof claim 6 , wherein Ris H or an optionally substituted Calkyl.8. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , ester claim 1 , hydrate claim 1 , or prodrug thereof claim 1 , wherein Ris H.9. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , ester claim 1 , hydrate claim 1 , or prodrug thereof claim 1 , wherein:{'sup': '1', 'Ris an amino acid side chain selected from the group consisting of valine, norvaline, leucine, norleucine, isoleucine, methionine, alanine, phenylalanine, tyrosine, tryptophan, serine, threonine, cysteine, lysine, arginine, histidine, aspartic acid, ...

SUBSTITUTED PYRROLIDINE-2-CARBOXAMIDES

There are provided compounds of the formula 3. The compound of whereinX is selected from H, F or Cl,Y is selected from H, F or Cl,{'sub': '1', 'Ris lower alkyl or substituted lower alkyl,'}{'sub': '3', 'Ris hydrogen or lower alkyl,'}{'sub': 5', '2', '2', 'n', '2', '2', 'n', '3, 'Ris selected from —(OCHCH)—OH or —(OCHCH)—OCHwherein n is from 45-55 and'}{'sub': '6', 'Ris hydrogen'}or a pharmaceutically acceptable salt thereof.5. A compound of selected from the group consisting of1-(Ethyl(isopropyl)carbamoyloxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate,4-{[(2R,3S,4R,5S)-3-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid di-tert-butoxy-phosphoryloxymethyl ester,4-{[(2R,3S,4R,5S)-3-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-[bis-(2-methoxy-ethyl)-carbamoyloxy]-ethyl ester,4-Methyl-piperazine-1-carboxylic acid 1-(4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoyloxy)-ethyl ester,1-Acetoxyethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate,Rac-1-(isobutyryloxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate,4-{[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid acetoxymethyl ester,1-(Cyclohexyloxycarbonyloxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate,Rac-1-(isopropoxycarbonyloxy)ethyl 4-((2R,3S ...

Process for the preparation of enantiomerically enriched cyclic beta-aryl or heteroaryl carbocyclic acids

The present invention relates to a process for the preparation of cis substituted cyclic β-aryl or heteroaryl carboxylic acid derivatives in high diastereo- and enantioselectivity by enantioselective hydrogenation in accordance with the following scheme wherein X, Ar, n, and m are defined herein and corresponding salts thereof.

QUATERNARY HETEROATOM CONTAINING COMPOUNDS

The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II): 3. The method of claim 2 , wherein:{'sup': '1', 'Ris selected from halogen and an optionally substituted group selected from alkyl, carbocyclyl, carbocyclylalkyl, cyanoalkyl, aralkyl, heteroaralkyl, hydroxyalkyl, haloalkyl, acylalkyl, alkoxycarbonylalkyl, and aryloxycarbonylalkyl;'}{'sup': 2', '12', '7', '8', '11, 'R, R, R, R, and Rare independently selected at each occurrence from hydrogen, halogen, hydroxyl, haloalkyl, cyano, alkyl, alkoxy, alkylthio, amide, amine, and carbocyclyl;'}{'sup': 3', '4', '5', '13', '14', '15, 'R, R, R, R, R, and Rare independently selected at each occurrence from hydrogen, halogen, haloalkyl, cyano, alkyl, alkoxy, alkylthio, amide, amine, aryloxy, and aralkyloxy;'}{'sup': 6', '9', '10, 'R, R, and Rare independently selected at each occurrence from hydrogen, hydroxyl, and optionally substituted alkyl, alkoxy, alkylthio, aryloxy, carbocyclyl, aryl, arylcarbonyl, aralkylcarbonyl, heteroaryl, aralkyl, heteroaralkyl, aralkyloxy, heteroaryloxy, acyl, arylcarbonyl, aralkylcarbonyl, acyloxy, alkylsulfonyl, arylsulfonyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, and amide.'}4. The method of claim 3 , wherein:{'sup': '1', 'Ris selected from halogen, alkyl, optionally substituted aralkyl, optionally substituted alkoxycarbonylalkyl, optionally substituted cyanoalkyl, and optionally substituted hydroxyalkyl; and'}{'sup': 6', '9', '10, 'R, R, and Rare independently selected at each occurrence from optionally substituted aralkyloxy, aralkoxycarbonyl, heteroaryloxy, acyl, arylcarbonyl, aralkylcarbonyl, arylsulfonyl, alkoxycarbonyl, and aryloxycarbonyl.'}5. The method of claim 4 , wherein:{'sup': '6', 'X is —NR—;'}{'sup': 7', '7, 'Z is selected from —C(O)— and —CRR—;'}{'sup': 8', '8, 'A at each occurrence is —CRR—;'}{'sup': 10', '11', '11, 'W is selected from —NR ...

SUBSTITUTED 2-[2-(PHENYL) ETHYLAMINO] ALKANEAMIDE DERIVATIVES AND THEIR USE AS SODIUM AND/OR CALCIUM CHANNEL MODULATORS

Substituted 2-[2-(phenyl)ethylamino]alkaneamide derivatives, pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing them are useful as sodium and/or calcium channel modulators for preventing, alleviating and curing pathologies wherein the above mechanisms play a pathological role. The compounds may be particularly useful for the prevention, alleviation, and curing of, for example, neurological, cognitive, psychiatric, inflammatory, urogenital and gastrointestinal diseases. 134-. (canceled)36. The method of claim 35 , wherein said cognitive or psychiatric disorder is caused by a dysfunction of a voltage-gated sodium channel.37. The method of claim 35 , wherein said cognitive or psychiatric disorder is caused by a dysfunction of a voltage-gated calcium channel.38. The method of claim 35 , wherein said patient is sensitive to unwanted side effects of MAO inhibitory effects.39. The method of claim 35 , wherein said disorder is a cognitive and/or psychiatric disorder selected from the group consisting of Mild Cognitive Impairment (MCI) claim 35 , depression claim 35 , bipolar disorder claim 35 , mania claim 35 , schizophrenia claim 35 , psychosis claim 35 , anxiety and addiction.40. The method of claim 35 , wherein the compound is administered with at least one other therapeutic agent.41. The method of claim 40 , wherein the at least one other therapeutic agent is an antipsychotic selected from the group consisting of haloperidol claim 40 , risperidone and clozapine.42. The method of claim 41 , wherein the antipsychotic is haloperidol or risperidone.43. The method of claim 35 , wherein the effective amount of the compound administered to the patient in need thereof (i) does not exhibit any MAO-inhibitory activity or (ii) exhibits a reduced MAO-inhibitory activity relative to safinamide or ralfinamide.44. The method of claim 35 , wherein the compound is 2-[2-(3-butoxyphenyl)-ethylamino]-N claim 35 ,N-dimethylacetamide or a pharmaceutically ...

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Substituted 2-[2-(phenyl) ethylamino] alkaneamide derivatives and their use as sodium and/or calcium channel modulators

Substituted 2-[2-(phenyl)ethylamino]alkaneamide derivatives, pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing them are useful as sodium and/or calcium channel modulators for preventing, alleviating and curing pathologies wherein the above mechanisms play a pathological role. The compounds may be particularly useful for the prevention, alleviation, and curing of, for example, neurological, cognitive, psychiatric, inflammatory, urogenital and gastrointestinal diseases.

Substituted tetracyclines

The invention in one embodiment is directed to a compound of formula (I) or a pharmaceutically acceptable salt thereof. The invention is also directed to a composition comprising the compound of formula I or a pharmaceutically acceptable salt, and methods of treating the indications listed herein.

HCV Protease Inhibitors and Uses Thereof

This invention relates to: (a) compounds of formula I and salts thereof that, inter alia, are useful as hepatitis C virus (HCV) inhibitors; (b) intermediates useful for the preparation of such compounds and salts; (c) pharmaceutical compositions comprising such compounds and salts; and (d) methods of use of such compounds, salts, and compositions. 3. The compound or salt of claim 1 , wherein each Ris independently selected from the group consisting of carbocyclyl claim 1 , heterocyclyl claim 1 , alkylcarbonyl claim 1 , alkenylcarbonyl claim 1 , alkynylcarbonyl claim 1 , alkyloxycarbonyl claim 1 , alkenyloxycarbonyl claim 1 , alkynyloxycarbonyl claim 1 , carbocyclylcarbonyl claim 1 , heterocyclylcarbonyl claim 1 , carbocyclyloxycarbonyl claim 1 , heterocyclyloxycarbonyl claim 1 , aminoalkylcarbonyl claim 1 , carbocyclylaminocarbonyl claim 1 , heterocyclylaminocarbonyl claim 1 , carbocyclylalkyloxycarbonyl claim 1 , heterocyclylalkyoxycarbonyl claim 1 , alkylcarbocyclylsulfonyl claim 1 , and alkylheterocyclylsulfonyl claim 1 , wherein:the amino portion of the aminoalkylcarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyloxycarbonyl, carbocyclylalkyloxycarbonyl, and heterocyclylalkyloxycarbonyl.4. The compound or salt of claim 1 , wherein each Ris independently selected from the group consisting of carbocyclyl claim 1 , heterocyclyl claim 1 , alkylcarbonyl claim 1 , alkyloxycarbonyl claim 1 , carbocyclylcarbonyl claim 1 , carbocyclyloxycarbonyl claim 1 , aminoalkylcarbonyl claim 1 , heterocyclylaminocarbonyl claim 1 , carbocyclylalkyloxycarbonyl claim 1 , and alkylcarbocyclylsulfonyl claim 1 , wherein:the amino portion of the aminoalkylcarbonyl optionally is substituted with one or two independently selected carbocyclylalkyloxycarbonyl.5. The compound or salt of claim 1 , wherein:{'sup': 8', 'B, 'Ris aminocarbonyl substituted with R; and'}{'sup': 'B', 'claim-text': the amino portion of the ...

ISOPRENYL COMPOUNDS AND METHODS THEREOF

Among other things, the present invention provides novel isoprenyl compounds capable of effectively modulating inflammatory responses and pharmaceutical, cosmetic, cosmeceutical and topical compositions comprising these isoprenyl compounds. Anti-inflammatory compounds of the present invention are useful in treating or preventing diseases or conditions associated with inflammation. Proinflammatory compounds of the present invention are useful in treating or preventing diseases or conditions associated with suppression of inflammatory responses. Thus, the present invention also provides methods useful in the treatment or prevention of diseases or conditions associated with inflammation as well as methods useful in the treatment or prevention of diseases or conditions associated with suppression of inflammatory responses. 2. (canceled)3. The compound according to claim 1 , wherein L is selected from a bivalent claim 1 , branched or unbranched claim 1 , saturated or unsaturated claim 1 , Chydrocarbon chain wherein one or more methylene units of L is independently replaced by —NH— claim 1 , —C(O)— claim 1 , —CH═CH— claim 1 , C-Ccycloalkylene claim 1 , C-Cheterocycloalkylene claim 1 , 8-10-membered bicyclic heterocyclic moiety claim 1 , an optionally substituted arylene and optionally substituted heteroarylene claim 1 , and wherein L is optionally substituted by one or more groups selected from halogen claim 1 , substituted or unsubstituted C-Calkyl claim 1 , and —NHC(O)CH.5. The compound according to claim 1 , wherein L is selected from a bivalent claim 1 , branched or unbranched claim 1 , saturated or unsaturated claim 1 , Chydrocarbon chain wherein one or more methylene units of L is independently replaced by —NH— claim 1 , —C(O)— claim 1 , —C(═CH)— claim 1 , —CH═CH— claim 1 , C-Ccycloalkylene claim 1 , 8-10-membered bicyclic heterocyclic moiety claim 1 , an optionally substituted arylene and optionally substituted heteroarylene claim 1 , and wherein L is optionally ...

SUBSTITUTED PYRROLIDINE-2-CARBOXAMIDES

There are provided compounds of the formula 2. The compound of whereinX is selected from H, F or Cl,{'sub': '1', 'Y is selected from H, F or C,'}{'sub': '1', 'Ris lower alkyl or substituted lower alkyl,'}{'sub': 3', '2', '3', '2', '2', '2', 'n', '2', '2', 'n', '3', '2', '2', 'n', '4', '2', '2', '2', '2', 'n', '2', '2', '2', 'n', '3', '2', '2', 'n', '3', '2', '2', 'n', '2', '2', '2', 'n', '3', '5', '2', '5', '2', '2', '5', '2', '5', '2', '2', 'n', '2', '2', '2, 'Ris selected from the group consisting of lower alkoxy, substituted lower alkoxy, alkylamino, dialkylamino, glucuronic acid, hexoses, aminohexoses, pyranoses, aminoglycosides, natural and unnatural amino acids, —OCHC(O)N(CH), —(OCHCH)—OH, —(OCHCH)—OCH, —(OCHCH)—OP(O)(OR), —OCHC(O)—(OCHCH)—OH, —OCHC(O)—(OCHCH)—OCH, —NH(CHCHO)—CH, —NH(CHCHO)—H, —OCHC(O)NH(CHCHO)—CH, —O—R, —OCH—R, OCHCH—R, —OCHC(O)—R, —NH(OCHCH)—NHand —OCHCH-amino acid, wherein n is from 3 to 60,'}{'sub': '4', 'Ris hydrogen or benzyl,'}{'sub': '5', 'Ris selected from the group consisting of heterocycles, substituted heterocycles, dialkylamino, alkylamino and aminoalkyl alcohols,'}or a pharmaceutically acceptable salt or ester thereof.3. The compound of whereinX is selected from H, F or Cl,Y is selected from H, F or Cl,{'sub': '1', 'Ris lower alkyl or substituted lower alkyl,'}{'sub': 3', '2', '3', '2', '2', '2', 'n', '2', '2', 'n', '3', '2', '2', 'n', '4', '2', '2', '2', '2', 'n', '2', '2', '2', 'n', '3', '2', '2', 'n', '3', '2', '2', 'n', '2', '2', '2', 'n', '3', '5', '2', '5', '2', '2', '5', '2', '5', '2', '2', 'n', '2', '2', '2, 'Ris selected from the group consisting of lower alkoxy, substituted lower alkoxy, alkylamino, dialkylamino, glucuronic acid, hexoses, aminohexoses, pyranoses, aminoglycosides, natural and unnatural amino acids, —OCHC(O)N(CH), —(OCHCH)—OH, —(OCHCH)—OCH, —(OCHCH)—OP(O)(OR), —OCHC(O)—(OCHCH)—OH, —OCHC(O)—(OCHCH)—OCH, —NH(CHCHO)—CH, —NH(CHCHO)—H, —OCHC(O)NH(CHCHO)—CH, —O—R, —OCH—R, OCHCH—R, —OCHC(O)—R, —NH(OCHCH)—NHand — ...

Lipids for therapeutic agent delivery formulations

The description is directed to ionizable lipids useful for enhancing the delivery of therapeutic agents in liposomes.

Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as alzheimer's disease, type 2 diabetes, and parkinson's disease

Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

PYRROLIDINE DERIVATIVES AS SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF

Disclosed are compounds of formula (I): 2. The compound of wherein Rrepresents C1-15 alkyl claim 1 , C1-15 alkenyl or C1-15 alkynyl substituted with one or more R.3. The compound of wherein Ris selected from carbocyclyl or aryl claim 2 , either of which is optionally substituted with one or more OH claim 2 , OR claim 2 , ═O claim 2 , NH claim 2 , N claim 2 , SH claim 2 , SOR claim 2 , halo claim 2 , CN claim 2 , NO claim 2 , NRR claim 2 , (NR)NRR claim 2 , NH(NR)NRR claim 2 , COR claim 2 , OC(O)R claim 2 , P(O)(OR) claim 2 , C1-9 alkyl optionally substituted with one or more OH claim 2 , OR claim 2 , ═O claim 2 , NH claim 2 , N claim 2 , halo claim 2 , CN claim 2 , NO claim 2 , NRR claim 2 , COR claim 2 , aryl or carbocyclyl groups.4. The compound of wherein Rrepresents C1-9 alkyl substituted with one or more aryl groups.5. The compound of wherein Rrepresents propyl phenyl or propyl methoxyphenyl.6. The compound of wherein Rrepresents a substituent selected from:hydrogenmethyl hexyl4-methyl pentylethylethyl cyclohexylpropylpropyl phenylpropyl methoxyphenylpropyl chlorphenylpropyl (bis)phenylpropanoyl phenylpropyl (p-ethylsulfamoyl)phenylpropyl (p-phenylthio)phenylbutylbutyl phenylhexyl6-hydroxy hexylhexyldansylhexyltosylamidehexyl biphenylsulfonamidehexyl phenoxyphenyl sulfonamideN-Boc propylaminenonylhydroxynonylmethoxyethoxyethylethylphenylbenzylbenzyl phenylphenoxy ethylethoxy dichlorophenyl.7. The compound of wherein Rrepresents C(O)NRR; CRRC(O)NRR; NRC(O)NRRor CRRNRC(O)NRR.8. The compound of wherein Rrepresents a substituent selected from:methylethylhydroxyethylpropylisopropylcyclopropylbutylisobutylallylmethylcyclohexylethyl ureaglycolamide.9. The compound of wherein one from R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Ris connected to Rto form an additional ring structure.10. The compound of wherein one from R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Ris connected to Rto form an additional ring ...

SYNTHESIS OF ACYCLIC AND CYCLIC AMINES USING IRON-CATALYZED NITRENE GROUP TRANSFER

The present invention provides novel synthetic methods for making acyclic secondary amines by reacting an azide with a compound bearing one or more C—H groups, catalyzed by a Fe-dipyrromethene complex. The acyclic secondary amines are thought to be formed through an intermolecular nitrene transfer. Also provided herein are methods of synthesizing protected (e.g., Boc- or Fmoc-protected) cyclic secondary amines (e.g., 5-, 6-, and 7-membered cyclic secondary amines) by reacting an azide that bears one or more C—H groups, catalyzed by a Fe-dipyrromethene complex. The protected cyclic secondary amines are thought to be formed through an intramolecular nitrene transfer and may be subsequently deprotected to yield cyclic secondary amines. 2. The method of claim 1 , wherein Ris optionally substituted alkyl.3. The method of claim 1 , wherein Ris adamantyl.4. The method of claim 1 , wherein Ris optionally substituted aryl.5. (canceled)6. The method of claim 1 , wherein Ris hydrogen.7. The method of claim 1 , wherein Rand Rare each hydrogen.8. The method of claim 1 , wherein Ris hydrogen or optionally substituted alkyl.9. The method of claim 1 , wherein Ris hydrogen.10. The method of claim 1 , wherein Ris optionally substituted alkyl.11. The method of claim 1 , wherein Ris optionally substituted aryl.12. (canceled)13. The method of claim 1 , wherein Rand Rare joined to form an optionally substituted carbocyclyl ring.14. The method of claim 1 , wherein L is R—O—R; and each occurrence of Ris independently optionally substituted alkyl.15. The method of claim 1 , wherein L is optionally substituted heterocyclyl.16. The method of claim 1 , wherein L is optionally substituted tetrahydrofuran or optionally substituted tetrahydropyran.17. The method of claim 1 , wherein L is optionally substituted heteroaryl.18. The method of claim 1 , wherein L is optionally substituted pyridine.22. The method of claim 21 , wherein the deprotection step comprises reacting an acidic compound claim 21 ...

NOVEL HIGH PENETRATION DRUGS AND THEIR COMPOSITIONS THEREOF FOR TREATMENT OF PARKINSON DISEASES

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate. 2. A pharmaceutical composition comprising a high penetration prodrug according to ; a compound comprising a structure selected from the group consisting of Structure NSAID-1 claim 1 , Structure NSAID-2 claim 1 , Structure NSAID-3 claim 1 , Structure NSAID-4 claim 1 , Structure NSAID-5 claim 1 , Structure NSAID-6 claim 1 , Structure NSAID-7 claim 1 , Structure NSAID-8 claim 1 , Structure NSAID-9 claim 1 , Structure NSAID-10 claim 1 , Structure NSAID-11 claim 1 , Structure NSAID-12 claim 1 , and Structure NSAID-13; an aromatic-L-amino-acid decarboxylase inhibitor selected from the group consisting of carbidopa claim 1 , benserazide claim 1 , difluromethyldopa claim 1 , and α-methyldopa; a catechol-O-methyl transferase inhibitor selected from the group consisting of entacapone and tolcapone; and a pharmaceutically acceptable carrier.3. The pharmaceutical composition according to claim 2 , the pharmaceutically acceptable carrier being selected from the group consisting of alcohol claim 2 , acetone claim 2 , ester claim 2 , cellulose claim 2 , mannitol claim 2 , croscarmellose sodium claim 2 , vegetable oil claim 2 , ...

ASYMMETRIC SYNTHESIS OF A SUBSTITUTED PYRROLIDINE-2-CARBOXAMIDE

The present invention provides an improved method for the large scale production of the compound 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid. 3. The process of claim 2 , wherein the insoluble base in step b) is anhydrous LiOH.5. The process of claim 4 , wherein the copper source in a) is a chiral copper catalyst selected from a complex formed by copper (I) acetate together with a chiral phosphine or bidentate phosphine claim 4 , such as PPh claim 4 , R- or S-BINAP claim 4 , R-BINAP claim 4 , R- or S-MeOBIPHEP; the insoluble base in step b) is anhydrous LiOH; the suitable hydroxide in c) is aqueous sodium hydroxide (NaOH); and Ris methyl or ethyl.6. (canceled)7. A pharmaceutical preparation comprising a compound of formula (I) produced by a process according to claim 1 , together with pharmaceutically acceptable excipient(s) and/or carrier(s).10. (canceled) The invention relates to a process for the preparation of 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid of the formula (I)as well as novel intermediates.The compound of formula I (herein sometimes designated as compound (I) or 5) is a non-peptidic, highly selective small-molecule antagonist of the protein-protein interaction between MDM2 and tumor suppressor protein p53. Inhibition of MDM2, the principal cellular antagonist of p53, leads to p53 pathway activation and apoptosis of cells carrying potential oncogenic mutations. This therapeutic approach (MDM2 inhibition) is currently under development as a novel strategy for cancer treatment. A previous synthesis of Compound I was reported in U.S. patent application Ser. No. 12/702,402, where Compound IIa is obtained from the racemate II by a chiral column chromatography method and coupled with Compound III followed by hydrolysis of the ...

PERFLUORO-TERT-BUTYL HYDROXYPROLINE

The present invention provides novel analogues of alpha amino acids, comprising a perfluoro-tert-butyl group, and molecules comprising the novel analogues. Also provided are a wide range of applications of the novel analogues in therapeutics, theranostics and pharmaceuticals as well as in imaging applications. In particular, the use of the novel analogues in detecting or modifying a target molecule is provided. 1: An analogue of an alpha amino acid , comprising a perfluoro-tert-butyl group.2: The analogue of claim 1 , wherein the analogue is selected from the group consisting of perfluoro-tert-butyl hydroxyproline claim 1 , perfluoro-tert-butylalanine claim 1 , perfluoro-tert-butyl homoserine claim 1 , perfluoro-tert-butyl glycine claim 1 , perfluoro-tert-butyl aspartate claim 1 , perfluoro-tert-butyl glutamate and perfluoro-tert-butyl tyrosine.3: The analogue of claim 1 , wherein the analogue is perfluoro-tert-butyl hydroxyproline (Hyp).4: The analogue of claim 3 , wherein the Hyp is selected from the group consisting of 2S claim 3 ,4R (Hyp) claim 3 , 2S claim 3 ,4S (Hyp) claim 3 , 2R claim 3 ,4R (Hyp) and 2R claim 3 ,4R (Hyp).5: The analogue of claim 1 , wherein the analogue is Fmoc perfluoro-tert-butyl hydroxyproline or Boc-perfluoro-tert-butyl hydroxyproline.6: A molecule comprising the analogue of .7: A composition comprising the molecule of .8: A method for diagnosing claim 7 , treating or preventing a disease or condition in a subject in need thereof claim 7 , comprising administrating to the subject an effective amount of the composition of .9: A method for detecting a target molecule in a sample claim 7 , comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) exposing the sample to a test molecule comprising the analogue of , wherein the analogue interacts with the target molecule, and'}(b) detecting the interaction, wherein the presence of the interaction indicates the presence of the target molecule in the sample.10: The method of claim 9 , ...

C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS

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

CARBOXAMIDE DERIVATIVES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B

Inhibitors of HBV replication of formula (I) 113.-. (canceled)14. A compound selected from the group consisting of:(S)—N-(3-bromo-4,5-difluorophenyl)-1-(2-oxo-2-(((R)-1,1,1-trifluoropropan-2-yl)amino)acetyl)pyrrolidine-3-carboxamide;(S)—N-(3-bromo-4,5-difluorophenyl)-1-(2-((3-methyloxetan-3-yl)amino)-2-oxoacetyl)pyrrolidine-3-carboxamide;(S)—N-(3-bromo-4,5-difluorophenyl)-1-(2-(tert-butylamino)-2-oxoacetyl)pyrrolidine-3-carboxamide;(3S)—N-(4-fluoro-3-methylphenyl)-1-{[(1-methylethyl)amino] (oxo)acetyl}pyrrolidine-3-carboxamide;(S)-1-(2-(cyclopentylamino)-2-oxoacetyl)-N-(4-fluoro-3-methylphenyl)pyrrolidine-3-carboxamide;(S)—N-(4-fluoro-3-methylphenyl)-1-(2-(((R)-1-hydroxypropan-2-yl)amino)-2-oxoacetyl)pyrrolidine-3-carboxamide;(3S)—N-(4-fluoro-3-methylphenyl)-1-{[(3-methyloxetan-3-yl)amino]-(oxo)acetyl}pyrrolidine-3-carboxamide;(3S)—N-(4-fluoro-3-methylphenyl)-1-[{[(1R)-1-methylpropyl]amino}(oxo)acetyl]pyrrolidine-3-carboxamide;(3S)—N-(4-fluoro-3-methylphenyl)-1-{oxo[(3S)-tetrahydrofuran-3-ylamino]-acetyl}pyrrolidine-3-carboxamide;(2S,3S)—N-(4-fluoro-3-methylphenyl)-2-methyl-1-{[(3-methyloxetan-3-yl)-amino](oxo)acetyl}pyrrolidine-3-carboxamide;(S)—N-(3-chloro-4,5-difluorophenyl)-1-(2-oxo-2-(((R)-1,1,1-trifluoropropan-2-yl)amino)acetyl)pyrrolidine-3-carboxamide;(3S)—N-(4-fluoro-3-methylphenyl)-1-{[(1-methylethyl)amino] (oxo)acetyl}piperidine-3-carboxamide;(S)—N-(3-chloro-4,5-difluorophenyl)-1-(2-oxo-2-((1-(trifluoromethyl) cyclopropyl)amino)acetyl)pyrrolidine-3-carboxamide;(S)—N-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(2-oxo-2-(((R)-1,1,1-trifluoropropan-2-yl)amino)acetyl)pyrrolidine-3-carboxamide;(S)—N-(3-chloro-4-fluorophenyl)-1-(2-oxo-2-(((R)-1,1,1-trifluoropropan-2-yl)amino)acetyl)pyrrolidine-3-carboxamide;(S)—N-(3-chloro-4,5-difluorophenyl)-1-(2-oxo-2-((1,1,1-trifluoro-2-methylpropan-2-yl)amino)acetyl)pyrrolidine-3-carboxamide;N-(4-fluoro-3-methylphenyl)-5-methyl-1-(2-((3-methyloxetan-3-yl)amino)-2-oxoacetyl)pyrrolidine-3-carboxamide;N-(3-chloro-4,5-difluoro- ...

PIPECOLIC ESTERS FOR INHIBITION OF THE PROTEASOME

The present disclosure relates to chemical compounds that modulate proteasome activity, pharmaceutical compositions containing such compounds, and use of these compounds and compositions for the treatment of disorders of uncontrolled cellular proliferation such as, for example, a cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 2. The compound of claim 1 , wherein n is 1.34-. (canceled)5. The compound of claim 1 , wherein Ris selected from (CH)Cyand Cy.6. The compound of claim 1 , wherein Ris CHCy.710-. (canceled)1315-. (canceled)16. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of and a pharmaceutically acceptable carrier.1720-. (canceled) This application claims the benefit of U.S. Provisional Application No. 62/623,861, filed on Jan. 30, 2018, the contents of which is incorporated herein by reference in its entirety.The Sequence Listing submitted Jan. 30, 2019 as a text file named “21105_0050P1_ST25.txt,” created on Jan. 30, 2019, and having a size of 496 bytes is hereby incorporated by reference pursuant to 37 C.F.R. § 1.52(e)(5).The proteasome is an essential protease that regulates intracellular processes and maintains biological homeostasis through the proteolytic degradation of misfolded and redundant proteins (Glickman et al. (2002) 82: 373-428). Inhibition of the proteasome induces apoptosis, which has translated in the clinic as a means to treat various cancers, most notably multiple myeloma and mantle cell lymphoma (Jankowska et al. (2013) 19: 1010-1028; Adams, J. (2004) 4: 349-360; Kuhn et al. (2011) 11: 285-295). The activities of the proteasome, the essential, multifunctional human proteolytic assembly, are not infrequently found to be affected by compounds with non-proteasomal primary targets. For example, this is the case with chloroquine (Sprangers et al. (2008) 47: 6727-6734), ...

ANTIVIRAL COMPOUNDS

The present invention provides compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection. 2. The compound of claim 2 , wherein Ris H and X is CH.3. The compound of claim 2 , wherein n is 2.4. The compound of claim 2 , wherein n is 1.5. The compound of claim 4 , wherein Ris —C(═O)N(R) claim 4 ,6. The compound of claim 4 , wherein Ris monocyclic or bicyclic heteroaryl claim 4 , optionally substituted with one or more R.7. The compound of claim 4 , wherein Ris —C(═O)OR.8. The compound of claim 7 , wherein R is lower alkyl.9. The compound of claim 8 , wherein Ris lower alkyl or cycloalkyl.10. The compound of claim 9 , wherein Ris cyclohexyl.11. A compound selected from the group consisting of:(2S,4S)-1-Cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic acid tert-butyl ester;(2S,4S)-1-(3,3-Dimethyl-butyl)-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic acid methyl ester;(2S,4R)-1-Cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-piperidine-2-carboxylic acid ethyl ester;(2S,4S)-1-Cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic acid ethyl ester;1-Hydroxy-naphthalene-2-carboxylic acid ((3S,5S)-5-benzooxazol-2-yl-1-cyclohexylmethyl-pyrrolidin-3-yl)-amide;(2S,4R)-1-Cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-piperidine-2-carboxylic acid methyl ester;1-Hydroxy-naphthalene-2-carboxylic acid [(3S,5S)-1-cyclohexylmethyl-5-(5-methyl-oxazol-2-yl)-pyrrolidin-3-yl]-amide;1-Hydroxy-naphthalene-2-carboxylic acid [(3S,5S)-1-cyclohexylmethyl-5-(5-phenyl-oxazol-2-yl)-pyrrolidin-3-yl]-amide;1-Hydroxy-naphthalene-2-carboxylic acid ((3S,5S)-1-cyclohexylmethyl-5-oxazol-2-yl-pyrrolidin-3-yl)-amide;(2S,4S)-1-Cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic ...

GLYCYRRHETINIMIDYL HYDROXYPROLINE ALKYL ESTERS AND PROTECTED DERIVATIVES THEREOF

The present invention is directed to glycyrrhetinimidyl hydroxyproline alkyl ester compounds and their protected derivatives and cosmetically acceptable salts thereof, methods of making the compounds, cosmetic compositions containing at least one of the compounds and methods of using the same to promote collagen production in human skin. The compounds and cosmetic compositions of the invention provide various advantageous properties to the human skin. 2. The compound of claim 1 , wherein Ris H— and Ris a methyl group.3. The compound of claim 1 , wherein Ris a protecting group selected from the group consisting of acetyl claim 1 , benzoyl claim 1 , benzyl claim 1 , beta-methoxymethyl ether claim 1 , methoxymethyl ether claim 1 , p-methoxy benzyl ether claim 1 , methylthiomethyl ether claim 1 , pivaloyl claim 1 , tetrahydropyranal claim 1 , trityl and silyl ether.4. The compound of claim 1 , wherein Ris a protecting group that is an acetyl group and Ris a methyl group.5. A cosmetic composition comprising up to 75% by weight of the compound of .6. The cosmetic composition of claim 5 , wherein Ris H— and Ris a methyl group.7. The cosmetic composition of claim 6 , further comprising a cosmetically acceptable carrier and wherein the compound is in an amount of about 0.001% to about 75% by weight of the composition.8. The cosmetic composition of claim 7 , comprising a collagen release promoter.10. The method of claim 9 , wherein the compound of formula (I) is deprotected to form the compound wherein Ris H—.11. The method of claim 10 , wherein Ris a methyl group.12. A method of promoting collagen production in human skin comprising the steps of applying the compound of to the skin of a person claim 1 , and administering a collagen release promoter to the person.13. The method of claim 12 , wherein the collagen release promoter is selected from the group consisting of Vitamin C claim 12 , copper claim 12 , manganese and hydroxyproline.14. The method of claim 12 , wherein the ...

Mdm2-based modulators of proteolysis and associated methods of use

The description relates to MDM2 binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the MDM2 E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

METHODS, COMPOUNDS, COMPOSITIONS AND VEHICLES FOR DELIVERING 3-AMINO-1-PROPANESULFONIC ACID

The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compound that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to the prevention and treatment of Alzheimer's disease 5. A method for treating Alzheimer's disease claim 1 , mild cognitive impairment claim 1 , Down's syndrome claim 1 , Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type claim 1 , cerebral amyloid angiopathy claim 1 , a degenerative dementia claim 1 , a dementia of mixed vascular and degenerative origin claim 1 , dementia associated with Parkinson's disease claim 1 , dementia associated with progressive supranuclear palsy claim 1 , dementia associated with cortical basal degeneration claim 1 , or diffuse Lewy body type of Alzheimer's disease claim 1 , comprising administering a therapeutically effective amount of a compound of to a human subject in need thereof.6. The method of claim 5 , which is for treating Alzheimer's disease claim 5 , mild cognitive impairment claim 5 , cerebral amyloid angiopathy claim 5 , or degenerative dementia.7. The method of claim 6 , which is for treating Alzheimer's disease.8. The method of wherein the compound is administered intratracheally claim 5 , intranasally claim 5 , ontologically claim 5 , rectally claim 5 , vaginally claim 5 , or orally.9. A pharmaceutical composition comprising a compound of together with a pharmaceutically acceptable carrier.10. The pharmaceutical composition of which is suitable for oral administration.11. The pharmaceutical composition of claim 9 , which is in the form of a hard shell gelatin capsule claim 9 , soft shell gelatin capsule claim 9 , cachet claim 9 , pill claim 9 , tablet claim 9 , lozenge claim 9 , powder claim 9 , granule claim 9 , pellet claim 9 , dragee claim 9 , which is ...

Proline-locked stapled peptides and uses thereof

The present invention provides a new type of alpha-helix nucleating cross-link (“staple”) formed by olefin metathesis of a proline derivative with an alkenyl side chain and another amino acid derivative with an alkenyl side chain. The proline derivatives as described herein have been found to be strong nucleators of alpha-helix formation. The invention also provides moieties for shielding the free amide N—H's at the N-terminus of an alpha-helix, thereby further stabilizing the helix. The proline derivatives, precursors prior to cross-linking, and the cross-linked peptides are provided as well as methods of using and preparing these compounds and peptides.

Automated Synthesis of Small Molecules Using Chiral, Non-Racemic Boronates

Provided are methods for making and using chiral, non-racemic protected organoboronic acids, including pinene-derived iminodiacetic acid (PIDA) boronates, to direct and enable stereoselective synthesis of organic molecules. Also provided are methods for purifying PIDA boronates from solution. Also provided are methods for deprotection of boronic acids from their PIDA ligands. The purification and deprotection methods may be used in conjunction with methods for coupling or otherwise reacting boronic acids. Iterative cycles of deprotection, coupling, and purification can be performed to synthesize chiral, non-racemic compounds. The methods are suitable for use in an automated chemical synthesis process. Also provided is an automated small molecule synthesizer apparatus for performing automated stereoselective synthesis of chiral, non-racemic small molecules using iterative cycles of deprotection, coupling, and purification. 1144-. (canceled)145. A method of deprotecting a pinene-derived iminodiacetic acid (PIDA) boronate , comprising:contacting a solution comprising the chiral, non-racemic PIDA boronate and a solvent with a solid-supported ammonium hydroxide reagent, thereby deprotecting the chiral, non-racemic PIDA boronate and forming a boronic acid and a PIDA.146. The method of claim 145 , wherein the solvent comprises THF.147. The method of claim 145 , wherein the solid-supported ammonium hydroxide reagent binds the PIDA.148. The method of claim 145 , further comprising the steps of removing the solvent by filtration claim 145 , leaving the boronic acid and PIDA ligand trapped inside the solid-supported ammonium hydroxide reagent; and adding additional solvent.149. The method of claim 148 , wherein the additional solvent is THF.150. The method of claim 145 , further comprising washing the solid-supported ammonium hydroxide reagent with an organic solution comprising an organic solvent and an acid in a quantity greater than that needed to neutralize the solid- ...

PYRROLIDINONES AND A PROCESS TO PREPARE THEM

This application is directed to a compound of Formula II Also disclosed is a process for preparing a compound of Formula II comprising using the compounds of Formulae IV and V Also disclosed is a method for preparing a compound of Formula I comprising contacting a compound of Formula II with a compound of a compound of Formula VI wherein A, AA, R, R, R, R, R, B, Band B, are as defined in the disclosure. 2. A compound of and salts thereof wherein{'sup': '1', 'Ris methyl, ethyl or propyl; and'}{'sup': '2', 'Ris H or methyl.'}3. A compound of and salts thereof selected from the group consisting ofmethyl (3R,4S)-1-methyl-2-oxo-4-[3-(trifluoromethyl)phenyl]-3-pyrrolidinecarboxylate; and(3R,4S)-1-methyl-2-oxo-4-[3-(trifluoromethyl)phenyl]-3-pyrrolidinecarboxylic acid.5. The process of wherein{'sup': '1', 'sub': 1', '4, 'claim-text': 'comprising alkylating a compound of Formula III wherein the alkylating agent is a dialkylsulfate.', 'Ris C-Calkyl;'}7. A compound of wherein{'sup': '1', 'Ris methyl, ethyl or propyl;'}{'sup': 3a', '3b, 'each Rand Ris independently methyl or ethyl; and'}{'sup': '4', 'Ris unsubstituted benzyl.'}8. A compound of that is1,3-dimethyl 2-[(1S)-2-[methyl(phenylmethyl)amino]-1-[3-(trifluoromethyl)phenyl]ethyl]propanedioate.14. The process of wherein{'sup': '1', 'Ris methyl, ethyl or propyl;'}comprising contacting a compound of Formula II-A wherein{'sup': '1', 'Ris methyl, ethyl or propyl'} 'with a compound of Formula VI.', 'prepared by the process as described in the Summary of the Invention for preparing a compound of Formula II-A'}15. The process of wherein a compound of Formula II-A is prepared using the method described in comprising alkylating a compound of Formula III.16. The process of wherein a compound of Formula II-A is prepared by first hydrolyzing the compound of Formula II-B.18. The method of wherein{'sup': '1', 'Ris methyl, ethyl or propyl'}comprising contacting a compound of Formula II-B wherein{'sup': '1', 'Ris methyl, ethyl or propyl; ...

HETEROCYCLIC INHIBITORS OF THE SODIUM CHANNEL

The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention concerns heterocyclic compounds (e.g., compounds according to any of Formulas (I)-(X) or Compounds (1)-(92) of Table 1) that are that are useful in treatment of conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotrophic lateral sclerosis, glaucoma, ischemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome.

ANTIBACTERIAL AGENTS

Antibacterial compounds of formula (I) are provided: 137-. (canceled)39. A compound of wherein A is —C(R claim 38 ,R)N(R claim 38 ,R).40. A compound of wherein A is —C(CH)NH.41. A compound of wherein A is —C(R claim 38 ,R)OR.42. A compound of wherein A is selected from the group consisting of:{'sub': 3', '10, '(1) substituted or unsubstituted C-C-cycloalkyl,'}(2) substituted or unsubstituted heterocyclyl, and(3) substituted or unsubstituted heteroaryl.44. (canceled)45. A compound of wherein G is selected from the group consisting of:(1) —C≡C—,(2) —C≡C—C≡C—,{'sup': 3G', '3G, '(3) —CR═CR—C≡C—, and'}{'sup': 3G', '3G, '(4) —C≡C—CR═CR—.'}46. A compound of wherein G is selected from the group consisting of:(1) —C≡C—,(2) —C≡C—C≡C—,(3) —CH═CH—C≡C—, and(4) —C≡C—CH═CH—.47. A compound of wherein G is —C≡C—.48. A compound of wherein G is —C≡C—C≡C—.49. A compound of wherein G is —CH═CH—C≡C—.50. (canceled)51. A compound of wherein G is —C≡C—CH═CH—.5257-. (canceled)58. A compound of wherein Ris H.59. A compound of wherein Y is substituted or unsubstituted aryl.60. A compound of wherein Y is substituted or unsubstituted phenyl.61. A compound of wherein Y is unsubstituted phenyl.62. (canceled)63. A compound of wherein D is substituted or unsubstituted heteroaryl.6467-. (canceled)68. A compound of wherein D is absent.6972-. (canceled)73. A compound of wherein L is absent.74. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier or diluent.75. A method for treating a subject with a gram-negative bacterial infection comprising administering to the subject in need thereof an antibacterially effective amount of a compound of or a pharmaceutical composition of .76. (canceled) This application is a continuation of U.S. patent application Ser. No. 12/635,551, filed Dec. 10, 2009, now pending, which is a continuation of International PCT Application No. PCT/US2008/066766, filed Jun. 12, 2008, which claims the benefit under 35 U.S.C. §119(e) of U.S. ...

BICYCLIC COMPOUNDS AS INHIBITORS OF PD1/PD-L1 INTERACTION/ACTIVATION

The compounds of Formula I is described herein along with their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof. The compounds described herein, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof are bicyclic compounds that are inhibitors of PD-1/PD-L1 interaction/activation. 7. The compounds of Formula I or its polymorphs claim 1 , stereoisomers claim 1 , tautomers claim 1 , prodrugs claim 1 , solvates claim 1 , and pharmaceutically acceptable salts thereof claim 1 , as claimed in claim 1 , is selected from a group consisting of:(S)-1-((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl) piperidine-2-carboxylic acid (1),N-(2-(((5-methoxy-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (2),(S)-1-((7-((3-(1-(3-(3,3-difluoropyrrolidin-1-yl)propyl)-1H-indol-4-yl)-2-methylbenzyl)oxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (3),(S)-1-((6-methyl-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (4),(S)-1-((6-chloro-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (5),Methyl 7-(((2-acetamidoethyl)amino)methyl)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-indene-5-carboxylate (6),(S)-1-((7-((3′-(3-(3,3-difluoropyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (7),(S)-1-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (8),(S)-1-((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (9)N-(2-(((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4- ...

COMPOUNDS AND METHODS OF USE

The present invention provides compounds useful in treating or preventing inflammation acne, bacterial conditions and promoting the appearance of healthy skin and compositions including these compounds. 2. The compound of claim 1 , wherein Y is selected from OH and —NH.3. The compound of wherein A is selected from —CH— claim 1 , —CHNH— claim 1 , N-methyl claim 1 , —O— and N(C-Calkylene carboxyl).4. The compound of wherein B is selected from —O— and unsubstituted O—C-Calkylene.5. The compound of wherein B is —CH—.6. The compound of wherein A and B together form a R-substituted or unsubstituted arylene or a R-substituted or unsubstituted heteroarylene having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur claim 1 , or a R-substituted or unsubstituted C-Ccycloalkylene or R-substituted or unsubstituted C-Cheterocycloalkylene having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.7. The compound of wherein A and B together form an unsubstituted C-Cheterocycloalkylene having 1-4 nitrogen atoms or an unsubstituted heteroarylene having 1-4 nitrogen atoms.8. The compound of wherein E and E′ are each methyl.9. The compound of wherein D is —OH.1113-. (canceled)1517-. (canceled)2129-. (canceled)30. The compound of claim 20 , wherein (2S)-1-{[(1R)-1-carboxy-2-{[(2E)-3 claim 20 ,7 claim 20 ,11 claim 20 ,15-tetramethylhexadec-2-en-1-yl]sulfanyl}ethyl]carbamoyl}pyrrolidine-2-carboxylic acid and (2R)-2-{[bis (carboxymethyl)carbamoyl]amino}-3-{[(2E)-3 claim 20 ,7 claim 20 ,11 claim 20 ,15-tetramethylhexadec-2-en-1-yl]sulfanyl}propanoic acid are excluded.3236-. (canceled)37. The compound of claim 31 , wherein (2S)-1-{[(1R)-1-carboxy-2-{[(2E)-3 claim 31 ,7 claim 31 ,11 claim 31 ,15-tetramethylhexadec-2-en-1-yl]sulfanyl}ethyl]carbamoyl}pyrrolidine-2-carboxylic acid and (2R)-2-{[bis(carboxymethyl)carbamoyl]amino}-3-{[(2E)-3 claim 31 ,7 claim 31 ,11 claim 31 ,15-tetramethylhexadec-2-en-1-yl]sulfanyl} ...

P2RX7 MODULATORS IN THERAPY

The present invention relates to compounds of formula (I), their enantiomers and their pharmaceutically acceptable salts, and their use in therapy, particularly for the prevention and/or treatment of cancer or inflammatory diseases. 2. The compound according to claim 1 , wherein the compound is an (S) enantiomer.3. The compound according to claim 1 , wherein the cycloalkyl is a cyclic saturated hydrocarbon group comprising from 1 to 12 carbon atoms.4. The compound according to claim 1 , wherein the aryl is a monocyclic or polycyclic aromatic hydrocarbon group claim 1 , which may be optionally substituted by at least one halogen atom claim 1 , one C1-C6 alkoxy radical claim 1 , and/or one C1-C6 halogenoalkyl radical.5. The compound according to claim 1 , wherein the aralkyl is not substituted claim 1 , or is substituted by at least one halogen atom claim 1 , one C1-C6 alkoxy radical claim 1 , one C1-C6 alkyl radical or one C1-C6 halogenoalkyl radical.6. The compound according to claim 1 , wherein the heteroaryl is an aryl group in which at least one carbon atom of the aromatic ring is substituted by a heteroatom.9. A pharmaceutical composition comprising the compound according to and a pharmaceutically acceptable carrier.10. A method for preventing and/or treating an inflammatory disease and/or a cancer in a subject in need thereof claim 1 , comprising administering to said subject at least one compound according to .11. The method according to claim 10 , wherein the inflammatory disease is a chronic inflammatory disease selected from the group consisting of rheumatoid arthritis claim 10 , Crohn's disease claim 10 , inflammatory bowel disease claim 10 , osteoartrosis and osteoporosis; and/or the cancer is selected from the group consisting of a colon cancer claim 10 , a colorectal cancer claim 10 , a melanoma claim 10 , a breast cancer claim 10 , a thyroid cancer claim 10 , a prostate cancer claim 10 , an ovarian cancer claim 10 , a lung cancer claim 10 , a ...

HETEROCYCLIC INHIBITORS OF THE SODIUM CHANNEL

The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention concerns heterocyclic compounds (e.g., compounds according to any of Formulas (I)-(III) or Compounds (1)-(65) of Table 1) that are that are useful in treatment of conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome. This application is a continuation of U.S. patent application Ser. No. 15/122,085 filed Aug. 26, 2016 which is a national phase application of PCT/US2015/017806 filed Feb. 26, 2014 which claims benefit to U.S. Provisional Patent Application No. 61/945,309 filed Feb. 27, 2014, and which is hereby incorporated by reference in its entirety.The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention relates to heterocyclic compounds (e.g., compounds according to any of Formulas (I)-(III) or Compounds (1)-(65) of Table 1) that are that are useful in treatment of diseases and conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome.Voltage-gated sodium (Nav) channels are present in neurons and excitable tissues where they contribute to processes such as membrane excitability and muscle contraction (Ogata et al., 88:365-77, 2002). Nine different transmembrane 3-subunits (Nav1.1-1.9) from a single Nav1 family combine with auxiliary β-subunits that modify channel ...

STAPLED AND STITCHED POLYPEPTIDES AND USES THEREOF

The present invention provides stapled polypeptides of the Formulae (I) and (VI): (I) (VI) and salts thereof; wherein the groups =====; R, R, R, R, R, R, R, R, R, R, R, L, L, L, L, X, v, w, p, m, s, n, t, and q are as defined herein. The present invention further provides methods of preparing the inventive stapled polypeptides from unstapled polypeptide precursors. The present invention further provides pharmaceutical compositions comprising a stapled polypeptide of Formula (I) or (VI), and methods of using the stapled peptides. The present invention also provides modifications of the staples post ring closing metathesis. 47-. (canceled)912-. (canceled)1518-. (canceled)2023-. (canceled)2526-. (canceled)2831-. (canceled)3336-. (canceled)3839-. (canceled)4245-. (canceled)4749-. (canceled)5254-. (canceled)55. A composition comprising a polypeptide of and a pharmaceutically acceptable excipient.56. A method of treating a disorder in a subject claim 1 , said method comprising administering an effective amount of a polypeptide of to a subject in need thereof.5758-. (canceled)6066-. (canceled)68. (canceled) This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional patent application, U.S. Ser. No. 61/779,917, filed Mar. 13, 2013, which is incorporated herein by reference.The important biological roles that peptides and polypeptides play as hormones, enzyme inhibitors and substrates, neurotransmitters, and neuromediators has led to the widespread use of peptides or peptide mimetics as therapeutic agents. A peptide's bioactive conformation, combining structural elements such as alpha-helices, beta-sheets, turns, and loops, is important as it allows for selective biological recognition of receptors or enzymes, thereby influencing cellcell communication and/or controlling vital cell functions, such as metabolism, immune defense, and reproduction (Babine et al., (1997) 97:1359). The alphahelix is one of the major structural components of peptides. However, ...

Prodrug of an ice inhibitor

This invention describes an ICE inhibitor prodrug (I) having good bioavailability. Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma.

CHARGED ION CHANNEL BLOCKERS AND METHODS FOR USE

The invention provides compounds, compositions, methods, and kits for the treatment of pain, itch, and neurogenic inflammation. 2. The compound of claim 1 , wherein Xis —NHC(O)—.3. The compound of or claim 1 , wherein each of Rand Ris independently selected from H claim 1 , halogen claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , and NRR; and each of Rand Ris independently selected from H claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , and Cheteroalkyl; or wherein at least one Ris present.4. The compound of any one of - claim 1 , wherein Ris Calkyl optionally substituted with halogen claim 1 , Ccyclic alkyl claim 1 , aryl claim 1 , or heteroaryl.5. The compound of any one of - claim 1 , wherein Ris H or Calkyl optionally substituted with halogen claim 1 , Ccyclic alkyl claim 1 , aryl claim 1 , or heteroaryl.6. The compound of any one of - claim 1 , wherein Ris Calkyl optionally substituted with halogen claim 1 , Ccyclic alkyl claim 1 , aryl claim 1 , or heteroaryl.7. The compound of any one of - claim 1 , wherein said compound is a compound in Table 1.11. The compound of claim 10 , wherein each of Rand Ris Calkyl optionally substituted with halogen claim 10 , cyclic alkyl claim 10 , aryl claim 10 , or heteroaryl.12. The compound of or claim 10 , wherein each of R claim 10 , R claim 10 , and Ris independently selected from H claim 10 , halogen claim 10 , Calkyl claim 10 , and CF; or wherein at least one Ris present; or wherein at least one Ris present.13. The compound of any one of - claim 10 , wherein said compound is a compound in Table 2.16. The compound of claim 15 , wherein Xis —NHC(O)—17. The compound of or claim 15 , wherein n is 0 or 1.18. The compound of any one of - claim 15 , wherein each of R claim 15 , R claim 15 , and Ris independently selected from H claim 15 , Calkyl claim 15 , and NRR; and each of Rand Ris independently selected from H claim 15 , Calkyl claim 15 , Calkenyl claim 15 , Calkynyl claim 15 , and ...

Apoe4-targeted theraputics that increase sirt1

Disclosed herein are compounds, compositions, and methods for treating neurodegenerative diseases, such as Alzheimer's disease.

PROCESSES FOR THE PREPARATION OF ARGINASE INHIBITORS AND THEIR SYNTHETIC INTERMEDIATES

Provided herein are processes and intermediates useful for the preparation of certain compounds, including a compound of formula 21 or formula 22 2. (canceled)4. (canceled)6. (canceled)8. (canceled)10. (canceled)12. (canceled)14. (canceled)16. (canceled)18. (canceled)20. (canceled)22. (canceled)24. (canceled)26. (canceled)28. (canceled)30. (canceled)32. (canceled)34. (canceled)36. (canceled)38. (canceled)39. A process for preparing a compound of formula 2 as defined in claim 37 , the process comprising esterifying L-malic acid under suitable conditions to form the compound of formula 2 or a salt thereof.40. (canceled)42. (canceled)4463-. (canceled)65. (canceled)67. (canceled)69. (canceled)71. (canceled)73. (canceled)75. (canceled)7783-. (canceled)8594-. (canceled) Compounds of general formula 21 and formula 22including pharmaceutically acceptable salts thereof, exhibit potent arginase inhibition.U.S. Pat. Nos. 10,065,974 and 10,494,339 describe benchtop preparation of compounds of the general formula 21. U.S. Pat. No. 10,287,303 describes preparation of compounds of the general formula 22. A need exists for economical synthetic procedures and intermediate compounds for the preparation of the compounds of formula 21 and formula 22 including pharmaceutically acceptable salts thereof for batch process scale-up. Such alternative synthetic procedures and intermediate compounds are provided herein.Provided herein is a process for preparing a compound of formula 21:or a pharmaceutically acceptable salt thereof, wherein:Also provided herein is a process for preparing a compound of formula 22:or a pharmaceutically acceptable salt thereof, wherein:In some embodiments, the process for preparing a compound of formula 21 or formula 22 comprises treating a compound of formula 20or a salt thereof, wherein:In some embodiments, the suitable conditions to deprotect the compound of formula 20 comprise treating with hydrogen and a palladium catalyst.In some embodiments, the process for ...

ROR GAMMA MODULATORS

There are described RORγ modulators of the formula (I), 2. A compound of claim 1 , wherein{'sup': 1', '1a', '1a, 'sub': '1-6', 'Ris halo, phenyl substituted with 0-3 R, or Calkyl substituted with 0-3 R;'}{'sup': 1a', 'a', 'b', 'a, 'sub': 3', '1-6', '2', 'r', '2', 'r, 'Ris, independently at each occurrence, hydrogen, CF, halo, Calkyl substituted with 0-3 R, —(CH)OR, and (CH)-phenyl substituted with 0-3 R,'}or a stereoisomer or pharmaceutically-acceptable salt thereof.3. The compound of claim 1 , wherein:{'sup': 2', '2c', '2a', '2b', '2d', '11', '11', 'a, 'sub': 2', '1-6', '2', 'p, 'Ris hydrogen, SOR, Calkyl substituted with 0-3 R, COR, —C(O)R, —C(O)NRR; or a 5-7 membered heterocycle comprising carbon atoms, and 1-4 heteroatoms selected from N, O, and S(O)substituted with 0-3 R,'}{'sup': 2a', 'a, 'sub': '1-6', 'Ris hydrogen or Calkyl substituted with 0-3 R;'}{'sup': 2b', 'a', 'a', 'a', 'a, 'sub': 1-6', '3-6', '2', 'r', 'p', '2', 'r, 'Ris hydrogen, Calkyl substituted with 0-3 R, Ccycloalkyl substituted with 0-3 R, or —(CH)-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)substituted with 0-3 R, or (CH)-phenyl substituted with 0-3 R;'}{'sup': 2c', 'a', 'a', 'a', 'a', 'a, 'sub': 1-6', '2-6', '3-10', '6-10', '2', 'r, 'Ris, independently at each occurrence, hydrogen, Calkyl substituted with 0-3 R, Calkenyl substituted with 0-3 R, Ccycloalkyl substituted with 0-3 R, Caryl substituted with 0-3 R, or a —(CH)5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R; and'}{'sup': 2d', 'd', '11', '11', 'd', 'a', 'a, 'sub': 1-6', '1-6', '3-6', '2', 'r, 'Ris, independently at each occurrence, hydrogen, Calkyl substituted with 0-3 R, Chaloalkyl, C(O)NRR, Ccycloalkyl substituted with 0-2 R, (CH)-phenyl substituted with 0-2 R, or a 5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R'}or a stereoisomer or pharmaceutically-acceptable salt ...

PSMA Imaging Agents

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

NEW 4-AMINO-4-OXOBUTANOYL PEPTIDES AS INHIBITORS OF VIRAL REPLICATION

The invention provides 4-amino-4-oxobutanoyl peptides of Formula I 2. The compound or salt of claim 1 , wherein{'sub': 1', '2', '2, 'claim-text': {'sub': 1', '3', '1', '2', '1', '4', '1', '4, '—COOH, C-Calkyl, C-Calkoxy, trifluoromethyl, mono- and di-C-Calkylcarboxamide, and mono- and di-C-Calkylcarbamate.'}, 'Rand Rare joined to form a pyrrolidine, piperidine, or piperazine ring, or a piperazine ring fused to a phenyl or cyclohexyl ring, each of which is substituted with 0 to 2 substituents independently chosen from halogen, oxo CONH,'}3. The compound or salt of claim 2 , wherein Rand Rare joined to form a pyrrolidine claim 2 , piperidine claim 2 , or piperazine ring claim 2 , or a piperazine ring fused to a phenyl claim 2 , each of which is optionally substituted with 0 to 2 substituents independently chosen from methyl claim 2 , —CONHand fluoro.6. A compound or salt of claim 1 , wherein{'sub': 3', '4', '1', '4', '3', '7', '0', '4, 'Ris hydrogen or methyl and Ris hydrogen, C-Calkyl, or (C-Ccycloalkyl)C-Calkyl.'}7. A compound or salt of claim 6 , wherein{'sub': 5', '1', '6', '3', '7', '0', '2', '0', '2, 'Ris C-Calkyl, (C-Ccycloalkyl)C-Calkyl, or (phenyl)C-Calkyl, each of which is unsubstituted; and'}{'sub': '6', 'Ris hydrogen or methyl.'}8. A compound or salt of claim 2 , wherein{'sub': '7', 'Ris hydrogen or methyl, and'}{'sub': 8', '1', '4', '3', '7', '0', '2', '0', '2, 'Ris C-Calkyl, (C-Ccycloalkyl)C-Calkyl, or (phenyl)C-Calkyl, each of which is unsubstituted; or'}{'sub': 7', '8', '1', '2', '2', '4', '1', '2, 'Rand Rare joined to form a 3- to 7-membered cycloalkyl ring or 3- to 7-membered heterocycloalkyl ring containing 1 or 2 heteroatoms independently chosen from N, S, and O, each of which cyclolalkyl or heterocycloalkyl ring is substituted with 0 to 2 substituents independently chosen from halogen, hydroxyl, amino, cyano, vinyl, C-Calkyl, C-Calkenyl, C-Calkoxy, trifluoromethyl, and trifluoromethoxy.'}9. A compound or salt of claim 8 , wherein Ris hydrogen and ...

CYCLIC AMIDES AS METAP-2 INHIBITORS

Compounds of the formula (I), in which R, R, R, R, R, R, X and Y have the meanings indicated in Claim , are inhibitors of methionine aminopeptidase and can be employed for the treatment of tumours. 2. Compounds according to in which{'sub': 2', '2', '2', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', '2', '2', '2', '2', '2', '2, 'sup': 1', '3', '3, 'Het denotes pyrazinyl, pyrazolyl, benzimidazolyl, pyridyl, indolyl, dihydroindolyl, benzofuranyl, tetrahydropyranyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indazolyl, imidazolyl, pyrrolyl, oxazolyl, oxadiazolyl, isoxazolyl, benzothiazolyl, piperidin-1-yl, pyrrolidin-1-yl, 3,4-dihydro-2H-pyrido[3,2-b]-1,4-oxazinyl, 3,4-dihydro-2H-benzo-1,4-oxazinyl, benzofuranyl, azetidinyl, 3-azabicylo[3.2.0]hexyl, pyrrolo[2,3-b]pyridinyl, tetrahydrofuranyl, tetrahydro-1,8-naphthyridinyl, 2,3-dihydrobenzoisothiazolyl, 1,2,3,4-tetrahydrobenzothiazinyl or hexahydrobenzo-1,3-dioxolyl, each of which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OA, CN, NH, NHA, NA, NO, CN, COOH, COOA, (CH)CONH, (CH)CONHA, (CH)CONA, NHCOA, COA, CHO, Het, SOA, SONH, SONHA, SONA, CONHNH, CONHAr, ═O and/or Ar,'}and pharmaceutically usable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.3. Compounds according to in which{'sup': '1', 'Hetdenotes pyridazinyl, pyrazolyl, pyridyl, piperazinyl, morpholinyl, pyrimidinyl, furyl, thienyl, imidazolyl, pyrrolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl, thiadiazole, piperidin-1-yl, pyrrolidin-1-yl, tetrahydropyranyl, 1,2-oxazinan-2-yl, 1,2,5-oxadiazinan-2-yl, 1,3-oxazinan-3-yl or hexahydropyrimidinyl, each of which is unsubstituted or mono-, di- or trisubstituted by A and/or OA,'}and pharmaceutically usable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.4. Compounds according to in which{'sup': 2', '4', '4', '2', '2', '4', '2, 'sub': 2', '2', 'n', '2', 'n, 'R ...

ANTIVIRAL COMPOUNDS

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds. 15. The compound of wherein each Xis absent.20. A pharmaceutical composition comprising the compound as described in or a pharmaceutically acceptable salt claim 1 , or prodrug thereof; and at least one pharmaceutically acceptable carrier.21. The pharmaceutical composition according to for use in treating disorders associated with HCV.22. The pharmaceutical composition of claim 20 , further comprising at least one additional therapeutic agent.23. The pharmaceutical composition of claim 22 , wherein said additional therapeutic agent is selected from the group consisting of interferons claim 22 , ribavirin analogs claim 22 , NS3 protease inhibitors claim 22 , NS5b polymerase inhibitors claim 22 , alpha-glucosidase 1 inhibitors claim 22 , hepatoprotectants claim 22 , non-nucleoside inhibitors of HCV claim 22 , and other drugs for treating HCV.24. The pharmaceutical composition according to claim 20 , further comprising a nucleoside analogue.25. The pharmaceutical composition according to claim 24 , further comprising an interferon or pegylated interferon.26. The pharmaceutical composition according to claim 25 , wherein said nucleoside analogue is selected from ribavirin claim 25 , viramidine claim 25 , levovirin claim 25 , a L-nucleoside claim 25 , and isatoribine and said interferon is α-interferon or pegylated interferon.27. A method of treating disorders associated with hepatitis C claim 1 , said method comprising administering to an individual a pharmaceutical composition which comprises a therapeutically effective amount of the compound as described in or a pharmaceutically acceptable salt claim 1 , or prodrug thereof. This application claims priority to U.S. Provisional Application No. 61/177,972, filed 13 May 2009; 61/224, ...

BENZIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING BENZIDINE DERIVATIVE FOR TREATING LIVER DISEASE CAUSED BY HEPATITIS C VIRUS

The disclosed compounds have antiviral activity against C-type virus, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient for preventing or treating liver disease caused by hepatitis C virus. The benzidine derivative according to the present invention has excellent antiviral activity against hepatitis C virus and exhibits excellent medicinal activity in the living body, and thus the pharmaceutical composition containing the same as an active ingredient can be useful as a pharmaceutical composition for preventing or treating liver disease, such as acute hepatitis C, chronic hepatitis C, cirrhosis, or hepatocellular carcinoma, caused by C-type virus. 2. The compound represented by formula 1 claim 1 , the optical isomer thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein:{'sup': 1', '2', '12', '13', '14, 'sub': 1-5', '1-5', '6-8, 'Rand Rare independently —H, —OH, halogen, Cstraight or branched alkyl, Cstraight or branched alkoxy, unsubstituted or substituted Caryl, —NRR, or —NHC(═O)R,'}{'sub': 6-8', '1-5', '1-5, 'in the said substituted Caryl, one or more substituents selected from the group consisting of Cstraight or branched alkyl, Cstraight or branched alkoxy, and halogen can be substituted;'}{'sup': 12', '13, 'sub': '1-3', 'Rand Rare —H, or Cstraight or branched alkyl;'}{'sup': '14', 'sub': '1-3', 'Ris —H, or Cstraight or branched alkoxy;'}{'sup': 1', '2, 'sub': '5-8', 'Rand Rcan form Cheterocycloalkyl containing one or more hetero atoms selected from the group consisting of N, O and S along with carbon atoms which are conjugated to the same;'}{'sup': 3', '4', '5', '6', '7', '8', '9', '10, 'sub': '1-5', 'R, R, R, R, R, R, R, and Rare independently —H, halogen, or unsubstituted or substituted Cstraight or branched alkyl in which one or more halogens are substituted,'}{'sup': 4', '7', '6', '9, ' ...

PHENYL DERIVATIVE

The compound of the formula (I-1): 2. The method according to claim 1 , wherein the ring 1 and the ring 2 each independently are (1) a benzene claim 1 , (2) cyclohexane or (3) pyridine ring.3. The method according to claim 1 , wherein the compound of formula (I-A) is 2-{4-[3-(4-fluorophenoxy)-5-{[(4-hydroxy-4-isobutyl-1-piperidinyl)carbonyl]amino}phenoxy]phenyl}-2-methylpropanoic acid or a salt thereof.4. The method according to claim 1 , wherein the protecting group T comprises a carbonyl group.5. The method according to claim 4 , wherein the protecting group T is a 2 claim 4 ,2 claim 4 ,2-trichloroethoxycarbonyl (Troc) group claim 4 , a phenoxycarbonyl group claim 4 , or a p-nitrophenoxycarbonyl group.6. The method according to claim 2 , wherein the compound of formula (I-A) is 2-{4-[3-(4-fluorophenoxy)-5-{[(4-hydroxy-4-isobutyl-1-piperidinyl)carbonyl]amino}phenoxy]phenyl}-2-methylpropanoic acid or a salt thereof.7. The method according to claim 1 , wherein the ring 1 and the ring 2 each independently are a benzene.8. The method according to claim 2 , wherein the ring 1 and the ring 2 each independently are a benzene.9. The method according to claim 1 , wherein the base is selected from the group consisting of pyridine claim 1 , triethylamine claim 1 , dimethylaniline claim 1 , dimethylaminopyridine claim 1 , diisopropylethylamine claim 1 , or a mixture thereof.10. The method according to claim 1 , wherein the organic solvent is selected from N claim 1 ,N-dimethylacetamide claim 1 , chloroform claim 1 , dichloromethane claim 1 , diethyl ether claim 1 , tetrahydrofuran claim 1 , and a mixture thereof.11. The method according to claim 2 , wherein the base is selected from the group consisting of pyridine claim 2 , triethylamine claim 2 , dimethylaniline claim 2 , dimethylaminopyridine claim 2 , diisopropylethylamine claim 2 , or a mixture thereof.12. The method according to claim 2 , wherein the organic solvent is selected from N claim 2 ,N-dimethylacetamide claim 2 ...

TETRAHYDRONAPHTHALENE DERIVATIVE

A compound represented by general formula (I-1): 3. The compound according to claim 1 , wherein Y is —CH— or —O— claim 1 , or a pharmaceutically acceptable salt thereof.4. The compound according to claim 1 , wherein ring 1 is a C3-10 carbocyclic ring claim 1 , or a pharmaceutically acceptable salt thereof.5. The compound according to claim 1 , wherein ring 3 is a C3-7 saturated carbocyclic ring which may be substituted with a C1-4 alkyl group claim 1 , or a 3- to 7-membered saturated heterocyclic ring which may be substituted with a C1-4 alkyl group claim 1 , or a pharmaceutically acceptable salt thereof.6. The compound according to claim 1 , wherein Z is a carboxyl group which may be substituted with a C1-8 alkyl group claim 1 , or a pharmaceutically acceptable salt thereof.7. A pharmaceutical composition comprising the compound represented by general formula (I-1) according to claim 1 , or a pharmaceutically acceptable salt thereof.8. The pharmaceutical composition according to claim 7 , which is an S1Pbinder and/or modulator.9. The pharmaceutical composition according to claim 7 , which is an agent for preventing and/or treating a S1P-mediated disease.10. The pharmaceutical composition according to claim 9 , wherein the S1P-mediated disease is neurodegenerative disease claim 9 , autoimmune disease claim 9 , infection or cancer.11. The pharmaceutical composition according to claim 10 , wherein the neurodegenerative disease is schizophrenia claim 10 , Binswanger's disease claim 10 , multiple sclerosis claim 10 , neuromyelitis optica claim 10 , Alzheimer's disease claim 10 , cognitive impairment claim 10 , amyotrophic lateral sclerosis or spinocerebellar ataxia.12. A method for preventing and/or treating a S1P-mediated disease claim 1 , comprising administering to a mammal an effective amount of the compound represented by general formula (I-1) according to claim 1 , or a pharmaceutically acceptable salt thereof.1314-. (canceled)15. The compound according to claim 2 ...

THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF

The invention provides compounds having the general Formula (I); 3. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris selected from the group consisting of F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —CN claim 1 , —OH claim 1 , —NH claim 1 , Calkyl and Chaloalkyl.5. The compound or pharmaceutically acceptable salt of claim 1 , wherein ring “A” is a Cheterocycle and is selected from the group consisting of azetidine claim 1 , pyrrolidine claim 1 , piperidine claim 1 , morpholine claim 1 , homopiperazine claim 1 , piperazine and 8-azabicyclo[3.2.1]octane claim 1 , and is optionally substituted.16. The compound or pharmaceutically acceptable salt of claim 1 , wherein:{'sup': 'o', 'sub': '1-6', 'Ris hydrogen or Calkyl;'}{'sup': 1', '2, 'sub': '1-8', 'Rand Rare each independently selected from the group consisting of hydrogen and Calkyl;'}{'sup': '3', 'Ris selected from the group consisting of hydrogen and F;'}{'sup': 4', '1', '4, 'sub': '1-4', 'Ris selected from the group consisting of hydrogen or Calkyl; or Rand Rare combined to form a 3- to 7-membered heterocycle ring as described above;'}{'sup': '5', 'sub': 1-8', '3-8, 'Ris selected from the group consisting of F, Cl, Calkyl, and Ccycloalkyl;'}{'sub': '1-6', 'L is Calkylene;'}the subscript m represents the integer 0 or 1;{'sup': 1', '2', '1', '2, 'Xand Xare each independently selected from the group consisting of absent and —O—, and wherein if the subscript m is 0 then one of Xor Xis absent;'}the ring “A” in is selected from the group consisting of:{'sub': '2-11', 'claim-text': [{'sup': 'AA', 'sub': 1-8', '1-8', '1-8, 'Ris independently selected from the group consisting of Calkyl, Chaloalkyl, Cheteroalkyl, F, Cl, Br and I;'}, 'n is an integer from 0 to 5;', {'sup': A', 'RA', 'RA', 'A', 'RA', 'RA', 'RAi', 'RA, 'sub': 6-10', '1-2', '1-2', '6-10', '1-4', '1-4', '1-4', '2', '1-4, 'Ris selected from the group consisting of (Caryl)-(X)—, and (5- to 10-membered heteroaryl)-(X)—, wherein said ...

Ketamine derivatives and compositions thereof

Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain.

PSMA Imaging Agents

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

ALANINE-BASED MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE

The description relates to Inhibitors of Apoptosis Proteins (IAPs) binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the IAP E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type. 1. A compound having a chemical structure:{'br': None, 'PTM-L-ILM,'}wherein ILM is a IAP E3 ubiquitin ligase binding moiety; L is a linker group coupling ILM and PTM; and PTM is a protein target moiety that binds to a target protein, a target polypeptide; or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate or polymorph thereof2. The compound of claim 1 , wherein the target protein or polypeptide has a biological function selected from the group consisting of structural claim 1 , regulatory claim 1 , hormonal claim 1 , enzymatic claim 1 , genetic claim 1 , immunological claim 1 , contractile claim 1 , storage claim 1 , transportation claim 1 , and signal transduction.3. The compound of claim 1 , wherein the PTM group binds a protein selected from the group consisting of B7.1 and B7 claim 1 , TINFRlm claim 1 , TNFR2 claim 1 , NADPH oxidase claim 1 , BclIBax and other partners in the apotosis pathway claim 1 , C5a receptor claim 1 , HMG-CoA reductase claim 1 , PDE V phosphodiesterase type claim 1 , PDE IV phosphodiesterase type 4 claim 1 , PDE I claim 1 , PDEII claim 1 , PDEIII claim 1 , ...

SOLID FORMS OF A PHARMACEUTICALLY ACTIVE COMPOUND

The present application discloses solid forms of compound (1) (1), methods for making them, as well as compositions comprising said solid forms. 2. The solid form according to claim 1 , characterized in that said solid form is a polymorph claim 1 , hydrate claim 1 , hemi-hydrate claim 1 , solvate claim 1 , hemi-solvate or pharmaceutically acceptable salt.31. The solid form according to daily claim 1 , characterized in that it is the amorphous form.4. The solid form according to claim 1 , characterized by the XRPD patterns at 2-theta values of 4.1 claim 1 , 6.9 claim 1 , 7.7 claim 1 , 9.1 claim 1 , 10.9 claim 1 , 13.5 claim 1 , 14.5 claim 1 , 17.2 claim 1 , 20.4 claim 1 , 22.3 25.5.5. The solid form according to claim 1 , characterized by the XRPD patterns at 2-theta values of 4.1 claim 1 , 5.0 claim 1 , 5.7 claim 1 , 6.3 claim 1 , 6.9 claim 1 , 7.9 claim 1 , 8.1 claim 1 , 9.0 claim 1 , 10.0 claim 1 , 14.3 and 19.5.6. The solid form according to claim claim 1 , characterized by the XRPD patterns at 2-theta values of 5.9 claim 1 , 8.3 claim 1 , 9.5 claim 1 , 10.1 claim 1 , 11.3 claim 1 , 14.2 claim 1 , 15.8 claim 1 , 17.6 claim 1 , 19.0 claim 1 , 19.4 claim 1 , 19.8 claim 1 , 20.3 and 25.5.7. The solid form according to claim claim 1 , characterized by the OXPD patterns at 2-theta values of 5.1 claim 1 , 8.0 claim 1 , 8.3 claim 1 , 8.8 claim 1 , 9.3 claim 1 , 10.0 claim 1 , 10.3 claim 1 , 13.7 claim 1 , 14.3 claim 1 , 18.7 claim 1 , 20.2 claim 1 , 20.8 and 27.6.8. The solid form according to claim claim 1 , characterized by the XRPD patterns at 2-theta values of 3.9 claim 1 , 7.8 claim 1 , 8.7 claim 1 , 9.1 claim 1 , 13.7 claim 1 , 14.5 claim 1 , 18.2 and 20.3.9. The solid form according to claim claim 1 , characterized by the XRPD patterns at 2-theta values of 5.5 claim 1 , 7.4 claim 1 , 14.5 claim 1 , 14.8 claim 1 , 15.6 claim 1 , 16.9 claim 1 , 17.8 claim 1 , 18.6 claim 1 , 1.9 claim 1 ,9 claim 1 , 20.5 claim 1 , 24.8 and 26.7.10. The solid form according to claim ...

COMPOSITIONS OF TROFINETIDE

This disclosure describes compounds of Formula (I), stereoisomers, side compounds thereof, pharmaceutical compositions and methods of manufacturing such compounds, using silylation reagents and producing compositions and products made using such methods. More particularly, this disclosure describes manufacture of trofinetide and side products, compositions and products containing such compounds, for pharmaceutical uses to treat neurodegenerative or neurodevelopmental disorders. 36-. (canceled)810-. (canceled)12. The composition according to claim 11 , wherein the compound of Formula (IIIa) claim 11 , or hydrate claim 11 , or pharmaceutically acceptable salt thereof claim 11 , is present in an amount between about 0.001 wt % and about 0.2 wt %.13. (canceled)14. (canceled)16. (canceled)18. (canceled)20. (canceled)22. (canceled)24. (canceled)25. The composition according to claim 2 , whereinsaid composition is obtained by:a) coupling H-MePro-OH and Z-Gly-OH in the presence of an activating reagent, silylating agent and a solvent, orb) coupling Z-Gly-OH and Suc-OH and then coupling the obtained Z-Gly-OSu and H-MePro-OH in the absence or presence of an activating reagent, a solvent and in the absence or presence of a silylating agent;c) coupling the obtained Z-Gly-MePro-OH and H-Glu-OH in the presence of an activating reagent, silylating agent and a solvent;d) obtaining Z-Gly-MePro-Glu-OH; ande) deprotecting Z-Gly-MePro-Glu-OH, to obtain the composition comprising the compound of Formula (Ia).2631-. (canceled)3341-. (canceled)42. The composition according to claim 25 , wherein deprotecting is achieved by hydrogenation.43. The composition according to claim 42 , wherein hydrogenation is performed in the presence of a Pd/C catalyst.44. The composition according to claim 42 , wherein hydrogenation is performed in the presence of a Pd/Si catalyst.45. (canceled)46. (canceled)47. The composition according to claim 42 , wherein the hydrogenation is performed using at least one ...

Selective androgen receptor modulators (sarms) and uses thereof

Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors. Also provided are methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.

PRODRUGS OF GAMMA-HYDROXYBUTYRIC ACID, COMPOSITIONS AND USES THEREOF

The present disclosure discloses prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof. 2. The composition of claim 1 , wherein the composition is a solid.3. The composition of claim 1 , wherein the composition further comprises a solvent for dissolving or dispersing the compound.4. The composition of claim 3 , wherein the solvent comprises water.5. The composition of claim 1 , wherein the composition is in a liquid dosage form.6. The composition of claim 1 , wherein the composition further comprises a flavoring agent claim 1 , sucrose claim 1 , lactose claim 1 , cellulose sugar claim 1 , mannitol claim 1 , maltitol claim 1 , dextran claim 1 , sorbitol claim 1 , starch claim 1 , agar claim 1 , alginates claim 1 , chitins claim 1 , chitosans claim 1 , pectins claim 1 , tragacanth gum claim 1 , gum arabic claim 1 , gelatins claim 1 , collagens claim 1 , casein claim 1 , albumin claim 1 , synthetic or semi-synthetic polymers or glycerides claim 1 , methyl cellulose claim 1 , hydroxypropylmethyl-cellulose claim 1 , or polyvinylpyrrolidone.7. The composition of claim 1 , wherein the composition further comprises a polymeric excipient.8. The composition of claim 1 , wherein the composition comprises a tablet claim 1 , a caplet claim 1 , a capsule claim 1 , a gel cap claim 1 , granules claim 1 , a pill claim 1 , a powder claim 1 , a lozenge claim 1 , a sachet claim 1 , a cachet claim 1 , a suspension claim 1 , an emulsion claim 1 , a solution claim 1 , a slurry claim 1 , or a syrup.9. The composition of claim 1 , wherein the composition is formulated in a unit dosage form.10. The composition of claim 9 , wherein the unit dosage form has a weight from 0.5 grams to 30 grams.11. The composition of claim 10 , wherein the composition is in a liquid dosage form.12. The composition of claim 11 , further comprising a pH adjusting agent selected from sodium hydroxide claim 11 , hydrochloric acid claim 11 , or malic acid.13. The composition of claim 1 , ...

PROLINE AMIDE COMPOUNDS AND THEIR AZETIDINE ANALOGUES CARRYING A SPECIFICALLY SUBSTITUTED BENZYL RADICAL

The present invention relates to proline amide compounds and their azetidine derivatives of formula I wherein the variables are as defined in the claims and the description. The invention further relates to a pharmaceutical composition containing such compounds, to their use as modulators, especially agonists or partial agonists, of the 5-HTreceptor, their use for preparing a medicament for the prevention or treatment of conditions and disorders which respond to the modulation of 5-HTreceptor, to a method for preventing or treating conditions and disorders which respond to the modulation of the 5-HTreceptor, and processes for preparing such compounds and compositions. 2. The compound as claimed in claim 1 , where Ris hydrogen.3. The compound as claimed in any of the preceding claims claim 1 , where Ris C-C-cycloalkyl which carries 1 or 2 substituents selected from the group consisting of fluoro and fluorinated methyl.4. The compound as claimed in any of or claim 1 , where Ris fluorinated C-C-alkyl claim 1 , where the carbon atom of the alkyl group which is bound to O does not carry any fluorine atom.5. The compound as claimed in any of or claim 1 , where Ris C-C-cycloalkyl-methyl claim 1 , where the cycloalkyl moiety carries 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 or 6 substituents selected from the group consisting of fluoro and fluorinated methyl.6. The compound as claimed in any of or claim 1 , where Ris phenyl-C-C-alkyl claim 1 , where the phenyl ring carries 1 claim 1 , 2 claim 1 , 3 or 4 substituents selected from the group consisting of fluoro and fluorinated methyl claim 1 , and may additionally carry one Cl substituent.7. The compound as claimed in any of or claim 1 , where Ris hetaryl-C-C-alkyl claim 1 , where hetaryl is a 5- or 6-membered monocyclic heteroaromatic ring containing 1 heteroatom selected from the group consisting of N and O as ring member claim 1 , where the heteroaryl ring carries 1 or 2 substituents selected from the group ...

PHENYL DERIVATIVE

The compound of the formula (I-1): 1. A method of preventing and/or treating a S1P2-mediated disease , comprising administering to a mammal an effective amount of 2-{4-[3-(4-fluorophenoxy)-5-{[(4-hydroxy-4-isobutyl-1-piperidinyl)carbonyl]amino}phenoxy]phenyl}-2-methylpropanoic acid , or a salt thereof.2. The method according to claim 1 , wherein the S1P2-mediated disease is a disease resulting from vascular constriction claim 1 , fibrosis claim 1 , peripheral arterial occlusive disease claim 1 , hepatitis claim 1 , hepatic cirrhosis claim 1 , or hepatic failure.3. The method according to claim 2 , wherein the disease resulting from vascular constriction is cerebral vasospastic disease claim 2 , cardiac vasospastic disease claim 2 , coronary vasospastic disease claim 2 , hypertension claim 2 , pulmonary hypertension claim 2 , myocardial infarction claim 2 , angina claim 2 , arrhythmia claim 2 , portal hypertension claim 2 , varix claim 2 , or ischemia-reperfusion injury.4. The method according to claim 2 , wherein the fibrosis is pulmonary fibrosis claim 2 , hepatic fibrosis claim 2 , kidney fibrosis claim 2 , myocardial fibrosis claim 2 , or skin fibrosis. This is a Divisional of U.S. patent application Ser. No. 15/089,690 filed Apr. 4, 2016 (allowed), which is a Divisional of U.S. patent application Ser. No. 14/592,100 filed Jan. 8, 2015 (issued as U.S. Pat. No. 9,340,499 on May 17, 2016), which is a Continuation of U.S. application Ser. No. 14/347,178 filed Mar. 25, 2014 (issued as U.S. Pat. No. 8,975,409 on Mar. 10, 2015), which is a National Stage Entry of PCT International Application No. PCT/JP2012/074968 filed Sep. 27, 2012, which claims benefit of Japanese Patent Application No. 2011-213987 filed Sep. 29, 2011 of which disclosures are incorporated herein by reference in their entirety.The present invention relates to a compound represented by the formula (I-1):wherein all the symbols have the same meanings as described hereinbelow, and a salt thereof, a ...

N-ACYLOXYSULFONAMIDE AND N-HYDROXY-N-ACYLSULFONAMIDE DERIVATIVES

The invention provides certain N-acyloxysulfonamide and N-hydroxy-N-acylsulfonamide derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the invention provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or develop of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy. 2. The compound of claim 1 , wherein L is —SO—.3. The compound of claim 1 , wherein Y is aryl and said aryl is unsubstituted or substituted with one or more substituents independently selected from W.4. The compound of claim 1 , wherein Y is aryl and said aryl is unsubstituted or substituted with one or two substituents independently selected from W.5. The compound of claim 1 , wherein Y is phenyl and said phenyl is unsubstituted or substituted with one or more substituents independently selected from W.6. The compound of claim 1 , wherein W is halo or —SO.7. The compound of claim 1 , wherein W is chloro claim 1 , bromo or —SO.8. The compound of claim 1 , wherein R is alkyl or phenyl claim 1 , wherein said alkyl and phenyl are unsubstituted or substituted with one or more halos.9. The compound of claim 2 , wherein Y is alkyl and said alkyl is unsubstituted or substituted with one or more substituents independently selected from W.10. The compound of claim 2 , wherein Y is alkyl and said alkyl is unsubstituted or substituted with one or more halos.11. The compound of claim 9 , wherein R is alkyl or phenyl claim 9 , wherein said alkyl and phenyl are unsubstituted or substituted with one or more substituents independently selected from halo claim 9 , nitro claim 9 , alkylsulfonyl and trihalomethyl.12. The compound of claim 1 , wherein the ...

PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF DIABETES

An object is to provide a novel compound which has a glycogen synthase activation ability, but activates a receptor PPAR to a low degree and is highly safe. Provided is a compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof: 4. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Arin the general formula (I) has 2 or 3 substituents which are halogen atoms.5. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein in the general formula (I) claim 1 , Rin the ring (II) represents a methyl group claim 1 , or Rin the ring (III) represents a hydrogen atom or a methyl group.6. The compound according to or a pharmaceutically acceptable salt thereof claim 3 , wherein Lin the formula (V-I) in the general formula (I) represents a bond or an alkylene group having 1 to 5 carbon atoms.7. The compound according to or a pharmaceutically acceptable salt thereof claim 3 , wherein in the general formula (I) claim 3 , each of Rand Rin the substituent (V-I) represents a hydrogen atom or a methyl group claim 3 , and Rin the substituent (VI-I) represents a hydrogen atom or a methyl group.8. A pharmaceutical composition comprising the compound according to or a pharmaceutically acceptable salt thereof.9. A pharmaceutical composition for treating diabetes mellitus claim 1 , comprising the compound according to or a pharmaceutically acceptable salt thereof.10. A glycogen synthase activator comprising the compound according to or a pharmaceutically acceptable salt thereof. The present invention relates to a novel compound having a glycogen synthase activation function, and to a pharmaceutical composition for treating diabetes mellitus comprising the compound.Diabetes mellitus is an important disease for people of today. The incidence of diabetes mellitus has recently been on an upward trend. Many drugs for treating diabetes mellitus have been developed based on the ...

Substituted biaryl compounds for inflammation and immune-related uses

The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein A, Y, L, R 1 , W 1 and W 2 are defined herein. These compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

Augmenting Moieties for Anti-Inflammatory Compounds

Augmented or synergized anti-inflammatory constructs are disclosed including anti-inflammatory amino acids covalently conjugated with other anti-inflammatory molecules such as nonsteroidal anti-inflammatory drugs, vanilloids and ketone bodies. Further conjugation with a choline bioisostere or an additional anti-inflammatory moiety further augments the anti-inflammatory activity. 121-. (canceled)23. (canceled)24. The conjugate of claim 22 , wherein said amino acid is selected from the group consisting of valine claim 22 , glycine claim 22 , proline and phenylalanine.25. The conjugate of claim 22 , wherein said augmenting moiety is an amino acid ester of H—OCHCHC(CH)or H—OCHCHSi(CH) claim 22 , or an amino acid amide of HNCHCHC(CH)or HNCHCHSi(CH).26. The conjugate of claim 22 , wherein said anti-inflammatory compound is selected from the group consisting of non-steroidal anti-inflammatory drugs (NSAIDs) claim 22 , vanilloids and ketone bodies.27. The conjugate of claim 26 , wherein said NSAID is selected from the group consisting of diclofenac claim 26 , ibuprofen claim 26 , naproxen claim 26 , and indomethacin; wherein said vanilloid is selected from the group consisting of vanillyl alcohol claim 26 , 3-methoxy-4-acetyloxybenzyl alcohol claim 26 , and vanillylamine; and wherein said ketone body is selected from the group consisting of 3-hydroxybutyrate and homologues thereof.30. (canceled)31. The conjugate of claim 28 , wherein Qis —CHCHC(CH)or —CHCHSi(CH).32. (canceled)33. A method of increasing the activity of an anti-inflammatory drug claim 28 , comprising conjugating said anti-inflammatory drug with an amino acid augmenting moiety to provide an amino acid conjugate of .3436-. (canceled)37. The method of claim 33 , wherein Qis selected from the group consisting of —CHCHC(CH)and —CHCHSi(CH).3839-. (canceled)40. The amino acid conjugate of claim 28 , wherein for the NSAID-CO— moiety claim 28 , the NSAID is selected from the group consisting of diclofenac claim 28 , ...

TETRACYCLINE COMPOUNDS

The present invention is directed to a compound represented by Structural Formula (I): 125-. (canceled)27. The compound of claim 26 , wherein:{'sup': 2', '3, 'sub': 1', '3', '1', '3', '1', '3, 'Rand Rtaken together with the nitrogen atom to which they are bound form a ring selected from pyrrolidine, piperidine, piperazine or morpholine, wherein the ring is optionally substituted with one or more substituents independently selected from fluoro, —OH, —C-Calkyl and —C-Calkylene-O—C-Calkyl, and wherein the ring is optionally fused to phenyl or spirofused to cyclopropyl.'}28. The compound of claim 27 , wherein:{'sup': 2', '3, 'Rand Rtaken together with the nitrogen atom to which they are bound form a ring selected from pyrrolidine and piperidine.'}29. The compound of claim 28 , wherein X is chloro.30. The compound of claim 29 , wherein:{'sup': 2', '3, 'Rand Rtaken together with the nitrogen atom to which they are bound form a ring selected from pyrrolidine and piperidine, wherein the ring is fused to phenyl.'}32. The compound of claim 26 , wherein:{'sub': 3', '10', '1', '3', '1', '3', '1', '3, 'the (4-7 membered) monocyclic heterocylic ring, or a (6-13 membered) bicyclic heterocylic ring, wherein the (4-7 membered) monocyclic heterocylic ring, or the (6-13 membered) bicyclic heterocyclic ring is substituted with at least one substituent independently selected from C-Ccarbocyclyl, (4-13 membered) heterocyclyl, and is optionally substituted with one or more substituents independently selected from fluoro, —OH, —C-Calkyl and —C-Calkylene-O—C-Calkyl.'}33. The compound of claim 32 , wherein:{'sup': 2', '3, 'the Rand Rtaken together with the nitrogen atom to which they are bound form a ring selected from pyrrolidine, piperidine, piperazine or morpholine.'}34. The compound of claim 33 , wherein:{'sub': 3', '10, 'the C-Ccarbocyclyl is a phenyl.'}35. The compound of claim 34 , wherein Rand Rtaken together with the nitrogen atom to which they are bound form a ring selected from ...

Non-aqueous Electrolyte Solution Additive, and Non-aqueous Electrolyte Solution for Lithium Secondary Battery and Lithium Secondary Battery which Include the Same

The present invention relates to a non-aqueous electrolyte solution additive, and a non-aqueous electrolyte solution for a lithium-ion battery and a lithium-ion battery which include the same, and particularly, to a non-aqueous electrolyte solution, which may remove an acid generated by the decomposition of a lithium salt while being able to suppress the dissolution of metal impurities causing failure in the battery by using and including a Lewis base compound containing a propargyl group as a non-aqueous electrolyte solution additive for a lithium-ion battery, and a lithium secondary battery in which transition metal dissolution in a positive electrode and a low-voltage phenomenon are improved. 8. A non-aqueous electrolyte solution for a lithium secondary battery , the non-aqueous electrolyte solution comprising:a lithium salt;an organic solvent; anda non-aqueous electrolyte solution additive,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein the non-aqueous electrolyte solution additive is the non-aqueous electrolyte solution additive of .'}9. The non-aqueous electrolyte solution for a lithium secondary battery of claim 8 , wherein the non-aqueous electrolyte solution additive is included in an amount of 0.05 wt % to 5 wt % based on a total amount of the non-aqueous electrolyte solution.10. The non-aqueous electrolyte solution for a lithium secondary battery of claim 9 , wherein the non-aqueous electrolyte solution additive is included in an amount of 0.5 wt % to 3 wt % based on the total amount of the non-aqueous electrolyte solution.11. A lithium secondary battery comprising a negative electrode claim 9 , a positive electrode claim 9 , a separator disposed between the negative electrode and the positive electrode claim 9 , and a non-aqueous electrolyte solution claim 9 ,wherein the positive electrode comprises a positive electrode active material selected from the group consisting of a lithium-nickel-manganese-cobalt-based oxide and a lithium-manganese- ...

Novel high penetration drugs and their compositions thereof for treatment of parkinson diseases

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

N-PHENYL-CARBOXAMIDE DERIVATIVES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B

Inhibitors of HBV replication of Formula (I) 4. A compound according to claim 1 , wherein Ris fluoro or methyl claim 1 , and Ris fluoro.5. A compound according to claim 1 , wherein X is —(SO)— claim 1 , and Ris —NRR.6. A compound according to claim 1 , wherein Ris a 3-7 membered saturated ring optionally containing one oxygen.7. A compound according to claim 1 , wherein Ris a branched C-Calkyl optionally substituted with one or more fluoro claim 1 , or Ris a C-Ccycloalkyl wherein said C-Ccycloalkyl is substituted with one or more fluoro or C-Calkyl substituted with one or more fluoro.8. A compound according to wherein claim 7 , Ris a branched C-Calkyl substituted with one or more fluoro.9. A method of treating an HBV infection comprising administering a therapeutically effective amount of at least one compound of .10. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier.11. A product containing (a) a compound of Formula (I) as defined in claim 1 , and (b) HBV inhibitor claim 1 , as a combined preparation for simultaneous claim 1 , separate or sequential use in the treatment of HBV infection.12. A compound according to claim 1 , wherein at least one of R claim 1 , Rand Ris fluoro claim 1 , and one other of R claim 1 , Rand Ris selected from the group consisting of hydrogen claim 1 , halogen claim 1 , CN claim 1 , CHF claim 1 , CHF claim 1 , CF claim 1 , C-Calkyl and cyclopropyl.13. A compound according to claim 1 , wherein Ris methyl and Ris fluoro.19. A compound according to claim 1 , wherein said compound is selected from the group consisting ofN-(4-fluoro-3-methyl-phenyl)-1-isobutylsulfonyl-pyrrolidine-3-carboxamide,(3S)—N-(4-fluoro-3-methyl-phenyl)-1-isobutylsulfonyl-pyrrolidine-3-carboxamide,(3R)—N-(4-fluoro-3-methyl-phenyl)-1-isobutylsulfonyl-pyrrolidine-3-carboxamide,(3S)—N-(4-fluoro-3-methyl-phenyl)-1-propylsulfonyl-pyrrolidine-3-carboxamide,(3S)-1-(cyclopropylmethylsulfonyl)-N-(4-fluoro-3-methyl- ...

Smac mimetic dimers and trimers useful as anti-cancer agents

The invention provides small molecule mimics of the Smac peptide that are dimer-like or trimer-like compounds having two or three amide-containing domains connected by a linker. These compounds are useful to promote apoptosis. The invention includes pharmaceutical compositions comprising such compounds and methods to use them to treat conditions including cancer and autoimmune disorders.

METHOD FOR PRODUCING OPTICALLY ACTIVE ALPHA-SUBSTITUTED PROLINE

The present invention aims to provide an industrial method practically suitable for producing optically active α-substituted prolines from an acyclic ketone compound by a small number of steps under mild conditions. The present invention relates to a production method of an optically active α-substituted proline (4) and/or an optically active α-substituted prolinamide (5), including (a) reacting an acyclic ketone compound (1) with at least one selected from ammonia, an ammonium salt, primary amine and a salt of primary amine, and a cyanating agent to give a cyclic nitrogen-containing compound (2), (b) hydrating the cyclic nitrogen-containing compound (2) to give an α-substituted prolinamide (3), and (c) resolving the α-substituted prolinamide (3) by one or more of (d) enzymatical hydrolysis, (e) resolution by diastereomeric salt formation, and (f) separation by column chromatography. The present invention relates to an industrial method for producing optically active α-substituted proline from an acyclic ketone compound. An optically active α-substituted proline produced by the present invention is a compound useful for peptide structural chemistry, or as a pharmaceutical intermediate.Optically active α-substituted prolines are considered to produce only a peptide having a low rotational degree of freedom and a limited conformation, since they tolerate only highly limited torsion angles in peptides containing them, and are drawing much attention in recent years (see, for example, non-patent document 1). Moreover, since they have structures with less fluctuation, they are considered to be useful as partial structures of highly selective pharmaceutical products, and have been actively utilized for drug discovery studies.As a synthesis method of optically active α-substituted prolines, a method using L-proline as a starting material, which includes protecting amino acid with pivalaldehyde, and performing alkylation using a strong base and an alkylating agent is known ( ...

ORGANIC ANION LITHIUM IONIC COCRYSTAL COMPOUNDS AND COMPOSITIONS

A cocrystal having the formula LiX.aM, or a solvate or hydrate thereof, wherein X is a conjugate base of an organic acid, M is a neutral organic molecule, and a is from 0.5 to 4, pharmaceutical compositions comprising such cocrystals, cocrystal solvates, or cocrystal hydrates, and methods of preparing such cocrystals, cocrystal solvates, or cocrystal hydrates, and such pharmaceutical compositions. 1. A cocrystal having the formula LiX.aM , or a solvate or hydrate thereof , wherein X is a conjugate base of an organic acid , M is a neutral organic molecule , and a is from 0.5 to 4.2. The cocrystal claim 1 , solvate or hydrate of wherein M is an amino acid.3. The cocrystal claim 1 , solvate or hydrate of wherein M is leucine.4. The cocrystal claim 1 , solvate or hydrate of wherein M is a neutral zwitterionic compound claim 1 , a xanthine claim 1 , a polyphenol claim 1 , or a flavonoid.5. The cocrystal claim 1 , solvate or hydrate of wherein X is acetate claim 1 , adipate claim 1 , diacetate claim 1 , alginate claim 1 , aminosalicylate claim 1 , anhydromethylenecitrate claim 1 , arecoline claim 1 , arginine claim 1 , ascorbate claim 1 , asparatete claim 1 , benzenesulfonate (benzene) claim 1 , benzoate claim 1 , bicarbonate claim 1 , bisulfate claim 1 , bitartrate claim 1 , butylbromide claim 1 , butyrate claim 1 , calcium edentate claim 1 , calcium edentate claim 1 , camphorate claim 1 , camsylate (camphorsulfonate) claim 1 , citrate claim 1 , dihydrochloride claim 1 , edentate claim 1 , edisylate (1 claim 1 ,2-ethanedisulfonate) claim 1 , estolate (lauryl sulfate) claim 1 , esylate (ethanesulfonate) claim 1 , fumarate claim 1 , gluceptate (glucoheptonate) claim 1 , gluconate claim 1 , digluconate claim 1 , glucuronate claim 1 , glutamate claim 1 , glycerophosphate claim 1 , glucollylarsanilate (p-glycollamidophenylarsonate) claim 1 , hexylresorcinate claim 1 , hydrabamine (N claim 1 ,N′-di(dehydroabietyl)ethylenediamine) claim 1 , hydroxynaphthoate claim 1 , ...

TREPROSTINIL PRODRUGS

Provided are novel prodrugs of treprostinil, as well as methods of making and methods of using these prodrugs. 146-. (canceled)48. A pharmaceutical composition claim 47 , comprising (A) an effective amount of the compound of and (B) a pharmaceutically acceptable carrier.49. A method of treating pulmonary hypertension comprising administering to a subject in need thereof the composition of .50. The method of claim 49 , wherein the composition is administered orally.51. The method of claim 49 , wherein the subject has detectable treprostinil plasma levels for at least 24 hours following said administration.52. The method of claim 49 , wherein the composition is administered by an injection.53. The method of claim 52 , wherein the administration is performed subcutaneously.54. The method of claim 53 , wherein said administration is continuous subcutaneous administration.55. The method of claim 52 , wherein said administration results in no or less pain at a site of the injection compared to administering treprostinil.56. The method of claim 49 , wherein the subject is a human being.57. The method of claim 49 , wherein upon said administration said compound converts to a metabolic product claim 49 , which consists essentially of treprostinil.58. The method of claim 57 , wherein said metabolic product consists of treprostinil.61. The method of claim 60 , wherein Ris C-Calkylene and each of Rand Rare H.62. The method of claim 49 , wherein Ris —C(O)—CHR—N(R) claim 49 , wherein Ris the side group of an amino acid.63. The method of claim 62 , wherein the amino acid is alanine claim 62 , valine or glycine.64. The method of claim 49 , wherein Ris a third drug moiety linked to the compound via an ester.65. The method of claim 49 , wherein the second drug moiety is a pain relief drug moiety.66. The method of claim 49 , wherein the second drug moiety is a nonsteroidal anti-inflammatory drug moiety.67. The method of claim 66 , wherein the second drug moiety is selected from the ...

PRODRUG OF AN ICE INHIBITOR

This invention describes an ICE inhibitor prodrug (I) having good bioavailability. 112.-. (canceled)14. The topical formulation of claim 13 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the active ICE inhibitor II claim 13 , or the pharmaceutically acceptable salt thereof.15. The topical formulation of claim 13 , wherein the topical formulation is an ointment.16. The topical formulation of claim 15 , wherein the pharmaceutically acceptable carrier claim 15 , adjuvant claim 15 , or vehicle is a mineral oil claim 15 , liquid petroleum claim 15 , white petroleum claim 15 , propylene glycol claim 15 , polyoxyethylene polyoxypropylene compound claim 15 , emulsifying wax claim 15 , or water claim 15 , or a combination thereof.17. The topical formulation of claim 13 , wherein the topical formulation is a cream or a lotion.18. The topical formulation of claim 17 , wherein the pharmaceutically acceptable carrier claim 17 , adjuvant claim 17 , or vehicle is a mineral oil claim 17 , sorbitan monostearate claim 17 , polysorbate 60 claim 17 , cetyl esters wax claim 17 , cetearyl alcohol claim 17 , 2-octyldodecanol claim 17 , benzyl alcohol claim 17 , or water claim 17 , or a combination thereof.19. The topical formulation of claim 13 , wherein the active ICE inhibitor II claim 13 , or the pharmaceutically acceptable salt thereof claim 13 , is in an amount of about 5% w/w to about 95% w/w of the topical formulation.20. The topical formulation of claim 13 , further comprising an additional agent claim 13 , wherein the additional agent is an anti-inflammatory agent claim 13 , a matrix metalloprotease inhibitor claim 13 , a lipoxygenase inhibitor claim 13 , a cytokine antagonist claim 13 , an immunosuppressant claim 13 , an anti-cancer agent claim 13 , an anti-viral agent claim 13 , a cytokine claim 13 , a growth factor claim 13 , an immunomodulator claim 13 , a prostaglandin claim 13 , an anti-vascular hyperproliferation compound claim 13 ...

INHIBITORS OF CREATINE TRANSPORT AND USES THEREOF

This invention relates to compounds that inhibit creatine transport and/or creatine kinase, pharmaceutical compositions including such compounds, and methods of utilizing such compounds and compositions for the treatment of cancer. 2. The compound of claim 1 , wherein Ris hydrogen.4. The compound of any one of to claim 1 , wherein Rcombines with Rwith the atoms to which they are attached to form an optionally substituted C-Ccycloalkyl ring.7. The compound of any one of to claim 1 , wherein Ris hydrogen claim 1 , hydroxyl claim 1 , or NH.8. The compound of any one of to claim 1 , wherein Ris hydrogen.9. The compound of any one of to claim 1 , wherein m is 1 and Ris deuterium claim 1 , optionally substituted C-Calkyl claim 1 , optionally substituted C-Calkenyl claim 1 , optionally substituted C-Calkynyl claim 1 , or Rand Rcombine with the atoms to which they are attached to form an optionally substituted C-Ccycloalkyl ring.10. The compound of claim 9 , wherein Ris deuterium.11. The compound of claim 10 , wherein Ris deuterium.12. The compound of or claim 10 , wherein Rand Rare both deuterium.13. The compound of claim 9 , wherein Ris optionally substituted C-Calkyl claim 9 , optionally substituted C-Calkenyl claim 9 , optionally substituted C-Calkynyl.14. The compound of claim 13 , wherein Ris methyl claim 13 , ethyl claim 13 , n-propyl claim 13 , iso-propyl claim 13 , —CD claim 13 , —CF claim 13 , —CHF claim 13 , —CHF claim 13 , —CH═CH claim 13 , or —C≡CH.15. The compound of or claim 13 , wherein Ris hydrogen or methyl.16. The compound of any one of to claim 13 , wherein Ris hydrogen.17. The compound of any one of to claim 13 , wherein Ris hydrogen claim 13 , NH claim 13 , or methyl.18. The compound of claim 9 , wherein Rand Rcombine with the atoms to which they are attached to form an optionally substituted C-Ccycloalkyl ring.19. The compound of claim 18 , wherein said optionally substituted C-Ccycloalkyl ring is an optionally substituted C-Ccycloalkyl ring.20. The ...

N-acyloxysulfonamide and n-hydroxy-n-acylsulfonamide derivatives

The invention provides certain N-acyloxysulfonamide and N-hydroxy-N-acylsulfonamide derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the invention provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or develop of a disease or condition. In some embodiments, the disease or condition is selected, from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy.

Radiolabeled Inhibitors of the Amino Acid Transporters ASCT1 and ASCT2

The invention features compounds and methods relating to hydroxy-proline analog inhibitors of the ASCT1 and ASCT2 neutral amino acid transporters useful for diagnostic purposes. These analogs are potent and selective inhibitors of ASCT2 and ASCT1-mediated amino acid transport as evidenced by significantly reduced glutamine or alanine transport-associated currents or radiolabeled substrate (amino acid) uptake in oocytes expressing ASCT2 or ASCT1. Selectivity has been established in the same manner whereby reduced substrate associated current or substrate uptake is unobserved in oocytes expressing ATA2, SN1, or EAAT(s) (excitatory amino acid transporter). The compounds and methods of the invention include radiolabeled inhibitors that can be used in research or clinical applications (e.g., for the treatment of cancer or ischemia-related central nervous system injury). 2. The compound of claim 1 , wherein said halogen is fluorine.3. The compound of claim 1 , wherein said halogen or radionuclide is fluorine-18.4. The compound of claim 1 , wherein said radionuclide is selected from the group consisting of carbon-11 claim 1 , nitrogen-13 claim 1 , oxygen-15 claim 1 , fluorine-18 claim 1 , zinc-62 claim 1 , copper-62 claim 1 , gallium-68 claim 1 , germanium-68 claim 1 , strontium-82 claim 1 , technicium-94m claim 1 , iodine 124 claim 1 , or rubidium-82.5. The compound of claim 3 , wherein said fluorine-18 has a specific activity of at least 1.0 Ci/mmol.6. The compound of claim 3 , wherein said fluorine-18 has a specific activity of at least 2.0 Ci/mmol.7. The compound of in combination with a pharmaceutically acceptable excipient.8. The compound of selected from the group consisting of trans-3-benzyloxy-cis-4-hydroxy-L-proline claim 1 , (2S claim 1 ,3S claim 1 ,4S)-3-phenoxy-4-hydroxy-proline claim 1 , cis-4-hydroxy-trans-3-methoxy-L-proline claim 1 , and cis-4-hydroxy-trans-3-isopropoxy-L-proline.10. The method of claim 9 , wherein said halogen is fluorine.11. The method ...