ГЕТЕРОЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ АНТАГОНИСТОВ CCR2B

Изобретение относится к новым соединениям общей формулы (I) или к их фармацевтически приемлемым солям, обладающим CCR2B антагонистической активностью, и к фармацевтической композиции на их основе. ! , ! где Р представляет собой фенил, возможно замещенный 1 или 2 заместителями, независимо выбранными из галогена, С1-4алкила, циано, трифторметила, С1-4алкокси и трифторметилтио, a R2 имеет значения, указанные в формуле изобретения. 2 н. и 14 з.п. ф-лы.

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 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.

НОВЫЕ ПИПЕРАЗИНАМИДНЫЕ ПРОИЗВОДНЫЕ

Изобретение относится к новым пиперазинамидным производным формулы (I), где Х представляет собой N или СН; Y представляет собой N или СН; R1 представляет собой низший алкил, фенил, фенил-низший алкил, где фенил необязательно может быть замещен 1-2 заместителями, независимо выбранными из группы, состоящей из галогена, низшего алкила; R2 представляет собой низший алкил, фенил, нафтил или гетероарил, выбранный из диметилизоксазолила, хинолинила, тиофенила или пиридинила, где фенил или гетероарил необязательно могут быть замещены 1 заместителем, независимо выбранным из группы, состоящей из галогена, низшей алкоксигруппы, фтор-низшего алкила, низшего алкокси-карбонила и фенила; R3 представляет собой фенил, пиридинил или пиразинил, где фенил, пиридинил или пиразинил замещены 1-2 заместителями, независимо выбранными из группы, состоящей из галогена, низшего алкила и фтор-низшего алкила; R4, R5, R6, R7, R8, R9, R10 и R11 независимо друг от друга представляют собой водород, а также к их физиологически ...

АЛЛОСТЕРИЧЕСКИЕ МОДУЛЯТОРЫ МЕТАБОТРОПНЫХ ГЛУТАМАТНЫХ РЕЦЕПТОРОВ

Изобретение относится к новым соединениям общей формулы I и их фармацевтически приемлемым солям. Соединения настоящего изобретения обладают свойствами положительного аллостерического модулятора mGluR5. В общей формуле I ! ! W представляет собой 6-членное гетероциклоалкильное кольцо с 1-2 гетероатомами, выбранными из N, О; R1 и R2 независимо представляют собой водород, C1-С6-алкил; Р и Q, каждый независимо, выбран из: ! ! R3, R4, R5, R6 и R7 независимо представляют собой водород; галоген; -CN; нитро; C1-С6-алкил; С3-С6-циклоалкил; галоген-С1-С6-алкил; 5-6-членный гетероарил с 1-2 атомами N в качестве гетероатомов; 6-членный гетероцикл с 2 гетероатомами, представляющими собой N, О; фенил, необязательно замещенный галогеном; нафтил; -OR8; где необязательно два заместителя вместе с находящимися между ними атомами образуют 9-10-членное бициклическое арильное или гетероарильное кольцо с 1-2 гетероатомами, выбранными из N, S; R8 представляет собой водород, C1-С6-алкил; D, Е, F, G и Н независимо ...

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 ...

СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНОГО ДИАЗАБИЦИКЛООКТАНА И ЕГО ПРОМЕЖУТОЧНОГО СОЕДИНЕНИЯ

Изобретение относится к области органической химии, способу получения производного диазабициклооктана формулы (IV), включающему взаимодействие соединения формулы (I) с ROH, выбранной из 1-гидроксипирролидин-2,5-диона, 2-гидрокси-3a,4,7,7a-тетрагидро-1H-изоиндол-1,3(2H)-диона, 2-гидроксигексагидро-1H-изоиндол-1,3(2H)-диона и 4-гидрокси-4-азатрицикло[5.2.1.0]дец-8-ен-3,5-диона, с получением соединения формулы (II), где Rпредставляет собой водород, OBn, P и Rявляются такими, как описано ниже, с последующим карбонилированием карбонилирующим агентом, выбранным из фосгена, дифосгена и трифосгена, с получением соединения формулы (II), где Rпредставляет собой ClCO- или ClCOCO-, OBn, P и Rявляются такими, как описано ниже, удаление защитной группы P и обработку основанием с получением соединения, представленного следующей формулой (III), и взаимодействие с соединением RONHс получением соединения формулы (IV), где OBn представляет собой бензилокси, P представляет собой NH-защитную группу, удаляемую ...

РАСТВОРИМЫЕ С5аR АНТАГОНИСТЫ

FIELD: biochemistry.SUBSTANCE: invention relates to compounds of Formula (I):in which R1is selected from a group consisting of H,R2is selected from a group consisting of H,R3is H,or; wherein two of R1, R2and R3are H, and one of R1, R2and R3differs from H, or its pharmacologically acceptable salts modulating C5a receptor. Pharmaceutical compositions containing such compounds and treatment methods are also described.EFFECT: compounds and pharmaceutical compositions containing such compounds can be used in medicine.25 cl, 2 dwg, 25 ex ...

ИНГИБИТОРЫ ФЕРМЕНТА ДИАЦИЛГЛИЦЕРИН О-АЦИЛТРАНСФЕРАЗА ТИПА 1

Изобретение относится к соединениям формулы (I) или их фармацевтически приемлемым солям, где Q является фенилом или пиридинилом; А является пиразолилом или триазолилом, где каждый А является независимо дополнительно незамещенным или замещенным 1 или 2 заместителями, представленными R, или А является формулой (a); Vявляется C(R), Vявляется N или C(R) и Vявляется N; иди Vявляется N, Vявляется C(R) и Vявляется N или C(R); Rявляется водородом, Rявляется водородом, Салкилом, -OR, -SR, арилом, выбранным из фенила, гетероарилом, выбранным из тиенила, или циклоалкилом, выбранным из циклопропила; Rявляется водородом или арилом, выбранным из фенила; Rявляется водородом или Салкилом; Rявляется водородом, Салкилом, -OH, -S(O)R, или гетероарилом, выбранным из тетразолила, где гетероарил соединен с атомом азота через углеродный атом кольца; R, R, R, R, R, R, R, R, R, R, Rи R, в каждом случае, являются независимо водородом, Салкилом или Сгалогеналкилом; и Rв каждом случае, является независимо водородом ...

ОПТИЧЕСКИ АКТИВНОЕ ПРОИЗВОДНОЕ ДИАЗАБИЦИКЛООКТАНА И СПОСОБ ЕГО ПОЛУЧЕНИЯ

Изобретение относится к оптически активному диазабициклооктановому производному формулы (F), где Rобозначает COR, COM или CONH, причем R обозначает метильную группу, трет-бутильную группу, аллильную группу, бензильную группу или 2,5-диоксопирролидин-1-ильную группу, и М обозначает атом водорода, неорганический катион, выбранный из лития, калия, натрия, или органический катион, причем органическим катионом является соль аммония, образованная из амина, выбранного из циклогексиламина; и Rобозначает бензильную группу или аллильную группу. Также изобретение относится к способу получения соединения формулы (F) и промежуточных соединений, к промежуточным соединениям, кристаллическим формам соединения формулы (F), а также применению соединения формулы (F) в качестве фармацевтического промежуточного соединения для получения ингибитора β-лактамазы, и к способу его получения. Технический результат: получены новые производные (2S,5R)-7-оксо-1,6-диазабицикло[3.2.1]октан-2-карбоновой кислоты, а также ...

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.

ИНГИБИТОРЫ МЕТАЛЛО-β-ЛАКТАМАЗЫ

Изобретение относится к новому ингибитору металло-β-лактамазы, который действует как лекарственное средство для ингибирования инактивации β-лактамовых антибиотиков и восстановления антибактериальных активностей. Производные малеиновой кислоты, имеющие общую формулу (I), имеют металло-β-лактамаза-ингибирующую активность. Возможно восстанавливать антибактериальные активности β-лактамовых антибиотиков в отношении бактерий, продуцирующих металло-β-лактамазу, комбинируя соединение общей формулы (I) с β-лактамовыми антибиотиками. Ингибитор металло-β-лактамазы представляет собой соединение формулы (I) или его фармацевтически приемлемую соль, в которой R1 обозначает С2-6-алкил; С3-7-циклоалкил, где указанный цикл может быть замещен гидроксильной группой или может быть конденсирован с арилом; гидроксиметил; - С1-3-алкиленфенил, где указанная фенильная группа может быть замещена гидроксильной группой, С1-6-алкильной группой, гидроксиметильной группой, группой -СООМ, где М обозначает атом водорода ...

БИЦИКЛИЧЕСКОЕ АРОМАТИЧЕСКОЕ СОЕДИНЕНИЕ, ФАРМАЦЕВТИЧЕСКАЯ И КОСМЕТИЧЕСКАЯ КОМПОЗИЦИИ

Изобретение относится к новым биоароматическим соединениям общей формулы I, где значения R1, R2, R3, X и Ar указаны в п.1 формулы. Они обладают активностью в областях дифференциации и пролиферации клеток. Описывается также фармацевтическая композиция, предназначенная для лечения дерматологических, ревматических, респираторных, сердечно-сосудистых и офтальмологических заболеваний, а также и косметическая композиция для гигиены тела и для ухода за волосами. 3 с. и 13 з.п.ф-лы, 4 ил.

ИНГИБИТОРЫ БЕТА-ЛАКТАМАЗ

В настоящей заявке описаны замещенные бициклические бета-лактамы формулы I: ! !которые являются ингибиторами β-лактамаз класса А и класса С, где X, R1 и R2 определены в тексте заявки, а также способ их получения. Соединения формулы I и их фармацевтически приемлемые соли применяют для получения фармацевтической композиции и в производстве лекарственного средства. Заявленные соединения применяются для лечения бактериальных инфекций необязательно в комбинации с β-лактамовым антибиотиком. В частности соединения могут быть использованы с такими β-лактамовыми антибиотиками, как, например, имипенемом, пиперациллином, или цефтазидимом, против микроорганизмов, устойчивых к действию β-лактамовых антибиотиков вследствие присутствия β-лактамаз. 6 н. и 22 з.п. ф-лы, 118 пр., 3 табл., 3 сх., 2 ил.

СТЕРЕОИЗОМЕРНЫЕ СОЕДИНЕНИЯ И СПОСОБЫ ЛЕЧЕНИЯ ЖЕЛУДОЧНО-КИШЕЧНЫХ РАССТРОЙСТВ И РАССТРОЙСТВ ЦЕНТРАЛЬНОЙ НЕРВНОЙ СИСТЕМЫ

... 1. Соединения формулы и их фармацевтически приемлемые соли, в которых связи 3 и 4 находятся в цис-положениях относительно друг друга; L представляет собой -(C1-C6-алкил)- (предпочтительно, -(C3-C5-алкил)-), -(C1-C6 -алкил)-C(O)- или же -C(O)-(C1-C6-алкил)-, где каждая из алкильных групп необязательно замещена 1 или 2 группами, независимо представленными галогеном, C1-C4 -алкокси или OH, и где один углерод в алкильной части L может быть заменен на -N(R9)-; R1 - галоген; R2 - аминогруппа, NH(C1 -C4-алкил) либо N(C1-C4-алкил)(C1-C4-алкил); R3 - OH либо C1-C4-алкокси; R4 - H или метил; и R5 представляет собой -O-C3-C8-циклоалкил, -O-гетероциклоалкил, гетероциклоалкил, арил, -O-арил, -N(R9)-(C0-C6-алкил)-C(O)-арил, либо -N(R9)-C0-C6-алкиларил, -O-гетероарил, -N(R9)-C1-C6(O)-гетероарил, либо -N(R9 )-C0-C6-алкилгетероарил, где каждая из циклических групп может быть незамещенной или замещенной по одной или более замещаемым позициям следующими заместителями C1 -C6-алкил, C1-C6-алкокси, галоген, ...

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

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

СПОСОБ ПОЛУЧЕНИЯ 5R-[(БЕНЗИЛОКСИ)АМИНО]ПИПЕРИДИН-2S-КАРБОНОВОЙ КИСЛОТЫ ИЛИ ЕЁ ПРОИЗВОДНОГО

Настоящая заявка относится к способам получения 5R-[(бензилокси)амино]пиперидин-2S-карбоновой кислоты или ее производных безвредным для окружающей среды путем. В способе применяют L-глутаминовую кислоту в качестве исходного вещества, причем ее сначала подвергают реакции эстерификации в присутствии кислотного реагента, а затем последовательно осуществляют реакцию с 2-галогенацетатом и средством для введения защитной группы для атома N или со средством для введения защитной группы для атома N и 2-галогенацетатом в основных условиях с получением соединения IV; затем полученное соединение IV подвергают внутримолекулярной конденсации с образованием кольца при воздействии сильного основания с получением защитная-группа-для-атома-пиперидин-5-он-2S-карбоксилата (V). Полученное соединение V применяют для получения 5R-[(бензилокси)амино]пиперидин-2S-карбоновой кислоты (или ее сложного эфира) посредством одного из нижеследующих путей. Путь 1: соединение V подвергают удалению защитной группы, конденсации ...

СПОСОБ ПОЛУЧЕНИЯ 5R-[(БЕНЗИЛОКСИ)АМИНО]ПИПЕРИДИН-2S-КАРБОКСИЛАТА И ЕГО ОКСАЛАТОВ

Изобретение относится к способам получения 5R-[(бензилокси)амино]пиперидин-2S-карбоксилата и его оксалата, где L-глутаминовую кислоту или натриевую соль L-глутаминовой кислоты в качестве исходного материала вводят в реакцию с монохлоруксусной кислотой в щелочных условиях посредством реакции замещения с получением N-карбоксиметил-L-глутаминовой кислоты (соединение III), затем соединение III вводят в реакцию со спиртом в присутствии кислотного реагента посредством реакции этерификации с получением сложного диэфира N-алкоксикарбонилметил-L-глутаминовой кислоты (соединения IV), под действием сильного основания соединение IV подвергают внутримолекулярной конденсации с образованием кольца, гидролизу с декарбоксилированием и этерификации с получением пиперидин-5-он-2S-карбоксилата (соединения V), соединение V подвергают конденсации с гидрохлоридной солью бензилоксиамина в присутствии щелочи с получением 5-[(бензилокси)имино]пиперидин-2S-карбоксилата (соединения VI), соединение VI подвергают восстановлению ...

3-МОНО- И 3,5-ДИЗАМЕЩЕННЫЕ ПИПЕРИДИНОВЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ РЕНИНА

... 1. Соединение формулы I ! ! где R1 каждый независимо от других (присутствует, если р>0) означает заместитель, выбираемый из группы, состоящей из заместителя формулы -(С0-С7)алкилен)-(Х)r-((С1-С7)-алкилен)-(Y)s-(С0-С7)алкилен)-Н, где C0-алкилен означает, что присутствует связь вместо связанного алкилена, r и s каждый независимо от другого означают 0 или 1, и каждый из Х и Y, если присутствует и независимо от других, означает -O-, -NV-, -S-, -С(=O)-, -C(=S), -O-СО-, -СО-O-, -NV-CO-; -CO-NV-; -NV-SO2-, -SO2-NV; -NV-CO-NV-, -NV-CO-O-, -O-CO-NV-, -NV-SO2-NV-, где V означает водород или незамещенный или замещенный алкил, как определено ниже; (С2-С7)алкенил, (С2-С7)алкинил, фенил, нафтил, гетероциклил, фенил- или нафтил- или гетероциклил(С1-С7)алкил или (С1-С7)алкилокси, ди(нафтил- или фенил)амино(С1-С7)алкил, ди(нафтил- или фенил(С1-С7)алкил)амино(С1-С7)алкил, бензоил- или нафтоиламино(С1-С7)алкил, фенил- или нафтилсульфониламино(С1-С7)алкил, где фенил или нафтил является незамещенным или замещенным ...

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 ...

ЗАМЕЩЕННЫЕ НИТРИРОВАННЫЕ КАТЕХОЛЫ, ИХ ПРИМЕНЕНИЕ В ЛЕЧЕНИИ НЕКОТОРЫХ РАССТРОЙСТВ ЦЕНТРАЛЬНОЙ И ПЕРИФЕРИЧЕСКОЙ НЕРВНОЙ СИСТЕМЫ И СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ

... 1. Соединение формулы I где R1 и R2, одинаковые или отличные друг от друга, обозначают водород, необязательно замещенный низший алканоил или ароил, необязательно замещенный низший алкоксикарбонил, или необязательно замещенный низший алкилкарбамоил; R3 обозначает водород или необязательно замещенную алканоильную или ароильную группу; R4 обозначает необязательно замещенную насыщенную или частично ненасыщенную низшую алкильную или арильную группу, или, взятый вместе с R3, образует необязательно замещенное насыщенное или частично ненасыщенное карбоциклическое кольцо; A обозначает кислород или группу NR5, где R5 обозначает NHR6, где R6 обозначает необязательно замещенную низшую алкильную или арильную группу, или группу OR7, где R7 обозначает водород, низший алкил или низший алканоил, или A обозначает необязательно замещенный алкилиден, когда R4 обозначает группу OR8, где R8 обозначает необязательно замещенную низшую алканоильную или ароильную группу, и его фармацевтически приемлемые соли. 2.

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 ...

ФТОРЗАМЕЩЕННЫЕ ЦИКЛИЧЕСКИЕ АМИНОСОЕДИНЕНИЯ И СПОСОБЫ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ И ИХ ПРИМЕНЕНИЯ

... 1. Фторзамещенное циклическое аминосоединение общей формулы I, его рацемат, R-изомер, S-изомер и фармацевтически приемлемая соль или их смесь:общая формула I,где m представляет собой целое число от 0 до 3, где m предпочтительно равен 0, 1 или 2;n представляет собой целое число от 0 до 3, где n предпочтительно равен 0, 1 или 2;X представляет собой (СН), СО или SO, где р представляет собой целое число от 0 до 3;Rпредставляет собой замещенный или незамещенный С-Сциклоалкил, замещенный или незамещенный С-Сциклоалкенил, замещенную или незамещенную 3-12-членную гетероциклическую группу, замещенный или незамещенный C-Cарил; заместитель(и) Rпредставляет(ют) собой 1, 2, 3, 4 или 5 одинаковых или отличающихся заместителей, независимо выбранных из группы, состоящей из галогена, С-Салкила, галогенозамещенного C-Cалкила, C-Cалкокси, C-Салкоксикарбонила, галогенозамещенной С-Салкокси, С-Салкенила, С-Салкинила, С-Сциклоалкила, циано, нитро, амино, гидроксила, гидроксиметила, карбоксила, меркапто, сульфонила ...

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 ...

Способ получения галоидзамещенных меркаптоациламинокислот

Способ получения производныхпРОлиНА

SULFONAMIDDERIVATE ALS ASPARTYLPROTEASE-INHIBITOREN

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

Substituierte Pipecoline-Säurederivate als HIV-Protease-Hemmer.

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

Hydantoinverbindungen

FKBP INHIBITOREN

VERFAHREN ZUR HERSTELLUNG VON 3-AMIDINOPHENYLALANIN-DERIVATEN

SUBSTITUIERTE HETEROCYCLISCHE VERBINDUNGEN UND DEREN VERWENDUNG ZUR BEHANDLUNG MULTIPLER MEDIKAMENTENRESISTENZ

MOLEKÜLMODELL FÜR VLA-4-INHIBITOREN

Neuroleptische Perhydro-1H-pyrido/1,2-a/pyrazine

Condensation products of tetracycline

Water-soluble aminomethyl derivatives of tetracycline having a low content of epitetra-cycline are prepared by reacting 1 mole of tetracycline, 1 to 2 moles of formaldehyde and 1 mole of an aliphatic or aromatic amino-acid, or a compound havin the general Formula I wherein n represents an integer from 1 to 3 inclusive, in a a lower aliphatic alcohol of 1 to 8 carbon atoms inclusive (e.g. EtOH or MeOH) and in the presence of sufficient amount of tertiary organic base (e.g. triethylamine, trimethylamine or pyridine) to impart to the mixture a pH from 7.5 to 8.5 at a temperature of 10 DEG to 50 DEG C. for 5 to 15 mins. Novel tetracycline derivatives of the Formula II wherein n is as above defined are prepared when one of the reactants is the compound of general Formula I. The derivatives are precipitated from the reaction mixture by cooling and acidification to pH 4-5. Examples of compounds prepared by this Mannich reaction are 3 - (carboxymethyl - 1 ...

Novel levo-1-n-butyl-2',6'-pipecoloxylidide and the Preparation Thereof

... 1,180,712. Levo - -1 - n - Butyl - 21,61 - pipecoloxylidide. STERLING DRUG Inc. 10 May, 1968 [18 May, 1967], No. 22420/68. Heading C2C. Novel levo - 1 - n - butyl - 21,61- pipecoloxylidide, free or substantially free from its optical antipode, and acid addition salts thereof are prepared (a) by reacting dl-21,61-pipecoloxylidide with O,O-dibenzoyl-d-tartaric acid to form a mixture of the diastereoisomeric O,O-dibenzoyl-d-tartrates, treating said mixture with boiling acetone, separating the acetone-insoluble dextro - 21,61 - pipecoloxylidide O,O - dibenzoyl - d-tartrate, isolating the levo-21,61-pipecoloxylidide O,O-dibenzoyl-d-tartrate from the acetone solution thereof, generating the levo-21,61- pipecoloxylidide base, e.g. with an inorganic base, from its O,O-dibenzoyl-d-tartrate and N- butylating said base, e.g. with n-butyraldehyde under catalytically hydrogenating conditions or with an n-butyl ...

Treatment

6,7-Di(lower alkoxy)-4-amino-2-(substituted piperidino) quinazolines

The title compounds wherein the substituent on the piperidino group is in, the 3- or 4-position and has the formula -(CH2)nCONR<1>R<2>,- O(CH2)nCONR<1>R<2> or - OCH(phenyl)CONR<1>R<2> wherein n is 0, 1 or 2; R<1> is hydrogen or lower alkyl; and R<2> is lower alkyl, phenyl, cycloalkyl, or lower alkyl substituted by certain stated substituents, with the proviso that any O, N or halogen atom in R<2> is separated by at least 2 carbon atoms from the nitrogen atom to which R<2> is attached; or R<1> and R<2> taken together with the nitrogen atom to which they are attached from a morpholino group optionally substituted by 1 or 2 lower alkyl groups, or a 1,2,3,4-tetrahydroiso -quinolyl group optionally substituted on the benzene ring portion by 1 or 2 lower alkoxy groups wherein phenyl groups are optional substituted are antihypertensives. Also claimed are the compounds' pharmaceutically acceptable bioprecursors and acid addition salts, processes for the preparation of the compounds, and pharmaceutical ...

AMINO ACID DERIVATIVES

Method of preparing amides of n-alkyl piperidine mono-carboxylic acid and n-alkyl pyrrolidine -a-monocarboxylic acid

Amides of the general formul and wherein R1 is an alkyl group, R2 an alkyl group of 1-5 carbon atoms or chlorine, R3 a hydrogen atom, an alkyl group of 1-5 carbon atoms, an alkoxy or a hydroxy group, and R4 a hydrogen atom, chlorine, an alkyl group of 1-5 carbon atoms or an alkoxy group, or in which R2, R3 and R4 are all hydrogen, are prepared by reacting an appropriately substituted aniline magnesium halide with the appropriate pyridine, piperidine, pyrrole or pyrrolidine monocarboxylic acid ester, which may or may not be N-alkylated, hydrolysing the reaction product and, where required, hydrogenating the heterocyclic ring and alkylating the nitrogen atom thereof. In the examples: (1) ethyl magnesium bromide and 2 : 6-dimethylaniline give 2 : 6-dimethylaniline magnesium bromide, this is refluxed with N-methylpipecolic acid ethyl ester and the product on hydrolysis with dilute Hcl gives N-methylpipecolic acid 2 : 6-dimethylanilide; (2) nipecotic ...

New carbonylated (AZA) cyclohexanes as dopamine D3 receptor ligands

Asymmetric ureas and medical uses thereof

3-Ox (adi) azolylpropanohydroxamic acids useful as procollagen c-proteinase inhibitors

"Diborane reduction of certain aryl piperidines".

A process for the preparation of a compound of formula (1); in which r3 is hydrogen, c1-6alkul or c1-6 alkylaryl, by reduction using diborane, of a compound of formula (11): in which r3 is as defined in relation to formula (1)and r4 is c1-6 alkyl.

HIV Protease inhibitors.

Hiv protease inhibitors, obtainable by chemical systhesis, inhibit or block the biologocal activity of the hiv protease enzyme, causing the replication of the hiv virus to terminate. These compounds as well as pharmaceutical compositions that contain these compounds and optionally other anti-viral agents as active ingrediants, are suitable for treating patients or hosts infected with the hiv virus, which is known to cause aids.

Substituted pipecolinic and acid derivatives as HIV protease inhibitors.

Disclosed herein are compounds of formula 1 wherein x is a terminal group, for example, an aryloxycarbonyl, an alkanoyl or an optionally mono or disubstituted carbamoyl, b is absent or an amino acid residue, for example, val or asn, r1 is hydrogen or a ring substituent, for example, fluoro or methyl, r2 is alkyl and y is a ring substituent for example, phenoxy, 2-pyridinylmethoxy, phenylthio or 2-pyridinylthio. The compounds inhibit the activity of human immunodeficiency virus (hiv)protease and interfere with hiv induced cytopathogenic effects in human cells. These properties render the compounds useful for combating hiv infections.

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

Piperazine and piperidine derivatives.

The present invention relates to piperazine and piperidine derivatives, which are especially useful for treating or preventing neuronal damage, particularly damage asssociated with neurological diseases. These compounds are also useful for stimulating nerve growth. The invention also provides compositions comprising the compounds of the present invention and methods of utilizing those compositions for treating or preventing neuronal damage or for stimulating nerve growth.

New carbonylated (AZA) cyclohexanes as dopamine D3receptor ligands

Heterocyclic compounds as inhibitors of rotamase enzymes.

Compounds of the formula: wherein r1, y, w, a and r2 are as defined above are inhibitors of rotamase enzymes in particular fkbp-12 and fkbp-52. The compounds therefore moderate neuronal regeneration and outgrowth and can be used for treating neurological disorders arising from neurodegenerative diseases and nerve damage.

FKBP inhibitors.

Compounds of formula (i), their salts and solvates, wherein the substituents are as described herein, are fkbp inhibitors.

SUBSTITUTED PIPECOLINIC ACID DERIVATIVES AS HIV PROTEASE INHIBITORS

Novel process

Caspase inhibitors and uses thereof.

This invention provides caspase inhibitors having the formula: (i)wherein ring a is an optionally substituted piperidine, tetrahydorquinoline or tettrahydroisoquinolone ring; r1 is hydrogen, chn2, r, or -ch2y; r is an optionally substituted group selected from an aliphatic group, an aryl group, an aralkyl group, a heterocyclic group, or an heterocyclylalkyl group; y is an electronegative leaving group; r2 is co2h, ch2co2h, or esters, amides or isosteres thereof; an optionally substituted aryl group; and r3 is hydrogen, an optionally substituted c1-6alkyl, f2, cn, aryl or r3 is attched to ar to form an unsaturated or partially saturated five or six membered fused ring having 0-2 heteroatoms. The compounds ae useful for treating caspase-mediated disease in mammals.

ASYMMETRIC UREAS AND MEDICAL USES THEREOF

NOVEL PIPERAZINE

A compound of formula (1)or the pharmaceutically acceptable salt thereof; wherein a,b,c,d,e,j,R1,R2,R3, and R4, are as defined above useful to treat inflammation and other immune disorders.

3-OX(ADI)AZOLYLPROPANOHYDROXAMIC ACIDS USEFUL AS PROCOLLAGEN C-PROTEINASE INHIBITORS

Compound of formula (I): wherein X is C1-6alkylene or C2-6 alkenylene, each of which is optionally substituted by one or more fluorine atoms; R is aryl or C3-8 cycloalkyl optionally substituted by one or more fluorine atoms; W is N or CZ; are procollagen C-proteinase (PCP) inhibitors useful in treating conditions mediated by PCP.

New carbonylated (AZA) cyclohexanes as dopamine D3 receptor ligands

Substituted aryl acylthioureas and related compounds; inhibitors of viral replication

HIV protease inhibitors

N,N' -substituted-1,3-diamino -2-hydroxypropane derivatives.

Disclosed are compounds of the formula (0, wherein the variables RN, RC, R1, R25, R2, and R3 are as defined herein. These compounds have activity as inhibitors of betasec-retase and are therefore useful in treating a variety of discorders such as Alzheimer's Disease.

P-SUBSTITUTED ASYMMETRIC UREAS AND MEDICAL USES THEREOF

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Phenoxyethyl piperidine compounds

3-Ox (adi) azolylpropanohydroxamic acids useful as procollagen c-proteinase inhibitors

Asymmetric ureas and medical uses thereof

Hiv protease inhibitors

Heterocyclially substituted benzoylureas, method for their production and their use as medicaments.

N,N'-substituted-1,3-diamino-2-hydroxypropane derivatives.

Substituted pipecolinic acid derivatives as hiv protease inhibitors

Derived from the quinolyl propyl piperidin and their use as antimicrobic agents.

FKBP inhibotors.

Process of obtaining new amilides.

Caspase inhibitors and uses thereof

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

P-SUBSTITUTED ASYMMETRIC UREAS AND MEDICAL USES THEREOF

Asymmetric ureas and medical uses thereof

Novel process

SUBSTITUTED PIPECOLINIC ACID DERIVATIVES AS HIV PROTEASE INHIBITORS

HIV protease inhibitors

New carbonylated (AZA) cyclohexanes as dopamine D3 receptor ligands

Fkbp inhibitors

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Substituted aryl acylthioureas and related compounds; inhibitors of viral replication

Phenoxyethyl piperidine compounds

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

P-SUBSTITUTED ASYMMETRIC UREAS AND MEDICAL USES THEREOF

SUBSTITUTED PIPERAZINE AS MODULATORS OF THE MELANOCORTINREZEPTORS

TYROSINDERIVATE

PROCEDURE FOR THE PRODUCTION OF NEW ALKYLENIMIN DERIVATIVES AND YOUR SALTS

MODEL OF MOLECULES FOR VLA-4-INHIBITOREN

PROCEDURE FOR THE PRODUCTION OF 3 - AMIDINOPHENYLALANIN DERIVATIVES

N-ACETYL-L-PIPECOLIC ACID AS PROMOTER OF THE PRODUCTION OF THE NEUROTROPHI FACTOR

PYRROLIDIN AND PIPERIDINDERIVATE AS NK1 ANTAGONIST

Novel N-substituted 3-piperidine- or 3- tetrahydropyridinecarboxylic acids and derivatives

Analogues of hexahydronicotinic acid (nipecotinic acid) are the novel compounds of the present invention. The analogues are GABA uptake inhibitors for use for the treatment of epilepsy and the like. The invention also provides pharmaceutical preparations for the treatment of epilepsy.

Design, synthesis and evaluation of procaspase activating compounds as personalized anti-cancer drugs

Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed that have lower neurotoxicity effects than other compounds.

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.

Diacylethylenediamine compound

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

Metallo-beta-lactamase inhibitors

A new metallo-β-lactamase inhibitor which acts as a medicament for inhibiting the inactivation of β-lactam antibiotics and recovering anti-bacterial activities is disclosed. The maleic acid derivatives having the general formula (I) have metallo-β-lactamase inhibiting activities. It is possible to recover the anti-bacterial activities of β-lactam antibiotics against metallo-β-lactamase producing bacteria by combining the compound of the general formula (I) with β-lactam antibiotics.

Compound inhibiting in vivo phosphorus transport and medicine containing the same

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

Compositions and methods useful for treating diseases

The present invention relates to a chemotherapeutic cancer treatment in which compounds of Formula Ia′, Ib′, Ic′, or II′ (referred to as a group as BH3Is) are administered to a mammal for the treatment of B-cell Lymphoma or other hematopoietic cancers, including diseases associated with MCL-1. In another aspect, the invention provides a method for treating particular types of hematopoietic cancers, such as B-cell lymphoma, using a combination of one or more compounds selected from the group consisting of compounds or Formula Ia, Ib, Ic, or II in combination with other therapies, for example, a class of therapeutics known as 26S proteosome inhibitors, such as, for example, Bortezomib. In another aspect the present invention relates to autoimmune treatment with pharmaceutical compositions comprising one or more compounds of Formula Ia′, Ib′, Ic′, or II′. In another aspect, this invention relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have unique in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.

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.

PYRENYLOXYSULFONIC ACID FLUORESCENT AGENTS

The invention provides a novel class of reactive fluorescent agents that are based on a pyrene sulfonic acid nucleus. The agents are readily incorporated into conjugates with other species by reacting the reactive group with a group of complementary reactivity on the other species of the conjugate. Also provided are methods of using the compounds of the invention to detect and/or quantify an analyte in a sample. In an exemplary embodiment, the invention provides multi-color assays incorporating the compounds of the invention. 125.-. (canceled)27. The compound of wherein s is 1 and t is 2.28. The compound of wherein the linker arm comprises a straight-chain claim 26 , saturated chain of atoms and includes unsubstituted polyalkylene.30. The compound of wherein s is 1 and t is 2.32. The conjugate of wherein s is 1 and t is 2.33. The conjugate of wherein the linker arm comprises a straight-chain claim 31 , saturated chain of atoms and includes unsubstituted polyalkylene.35. The conjugate of claim 34 , wherein the linker arm comprises a cleavable group.36. The conjugate of claim 34 , wherein the linker arm comprises —C(O)NH— claim 34 , —C(O)O— claim 34 , —NH— claim 34 , —S— claim 34 , or —O—.37. The conjugate of claim 34 , wherein s is 1 claim 34 , and t is 2.38. A kit for the detection of an analyte in a sample claim 26 , wherein said kit comprises a compound of .39. A kit for the detection of an analyte in a sample claim 29 , wherein said kit comprises a compound of .40. A kit for the detection of an analyte in a sample claim 31 , wherein said kit comprises a conjugate of .41. A kit for the detection of an analyte in a sample claim 34 , wherein said kit comprises a conjugate of . NOT APPLICABLENOT APPLICABLENOT APPLICABLEThe present invention relates to novel fluorescent compounds that have utility in detecting one or more selected analytes in a sample. The invention is of use in a variety of fields including immunology, diagnostics, molecular biology and fluorescence ...

METHOD FOR PRODUCING OPTICALLY ACTIVE 3-AMINOPIPERIDINE OR SALT THEREOF

The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing. 118.-. (canceled) The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate, and to intermediates useful for producing the 3-aminopiperidine.As methods for producing an optically active 3-aminopiperidine or salt thereof, or a derivative of optically active 3-aminopiperidine, for example, the following methods are known:1) a method, wherein L-ornithine monohydrochloride is methyl-esterified, and then (S)-3-amino piperidone is obtained by chromatography with an ion exchange resin, the (S)-3-amino piperidone is reacted with lithium aluminum hydride to be (S)-3-aminopiperidine, an inorganic salt is removed by filtration, and the target compound is purified (Non-patent Document 1);2) a method, wherein ethyl nipecotate is optically resolved using L-tartaric acid, the nitrogen atom is protected with benzyloxycarbonyl group, the ethyl ester is hydrolyzed in alkaline condition, Curtius rearrangement is carried out using ...

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.

Guanidine compound

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

C5ar antagonists

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

PRODRUGS OF A PIPERIDINYL DERIVATIVE AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY

The present application describes prodrugs of the compound of formula (I): 3. A pharmaceutical composition comprised of a pharmaceutically acceptable carrier and a therapeutically effective amount of one or more of the compounds of .4. A pharmaceutical composition comprised of a pharmaceutically acceptable carrier and a therapeutically effective amount of one or more of the compounds of .5. A method for modulation of chemokine or chemokine receptor activity comprising administering to a patient in need thereof a therapeutically effective amount of one or more of the compounds of .6. The method of claim 5 , wherein the chemokine or chemokine receptor activity is CCR-1 or CCR-1 receptor activity.7. A method for treating a disorder comprising administering to a patient in need thereof a therapeutically effective amount of one or more of the compounds of ; wherein said disorder is selected from osteoarthritis claim 1 , aneurysm claim 1 , fever claim 1 , cardiovascular effects claim 1 , Crohn's disease claim 1 , congestive heart failure claim 1 , autoimmune diseases claim 1 , HIV-infection claim 1 , HIV-associated dementia claim 1 , psoriasis claim 1 , idiopathic pulmonary fibrosis claim 1 , transplant arteriosclerosis claim 1 , physically- or chemically-induced brain trauma claim 1 , neuropathic pain claim 1 , inflammatory bowel disease claim 1 , alveolitis claim 1 , ulcerative colitis claim 1 , systemic lupus erythematosus claim 1 , nephrotoxic serum nephritis claim 1 , glomerulonephritis claim 1 , asthma claim 1 , multiple sclerosis claim 1 , atherosclerosis claim 1 , rheumatoid arthritis claim 1 , restenosis claim 1 , organ transplantation claim 1 , multiple myeloma claim 1 , colorectal cancer claim 1 , hepatocellular cancer and other cancers.8. A method for treating inflammatory diseases comprising administering to a patient in need thereof a therapeutically effective amount of one or more of the compounds of .9. A method for preparing a medicament for the treatment ...

Analogs of Benzoquinone-Containing Ansamycins and Methods of Use Thereof

The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

N-ADAMANTYL BENZAMIDES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE

Novel substituted benzamide based inhibitors, their use in therapy, pharmaceutical compositions comprising the compounds, the use of said compounds in the manufacture of medicaments, and therapeutic methods comprising the administration of said compounds are described. The present compounds modulate the activity of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and are accordingly useful in the treatment of diseases in which such a modulation is beneficial, such as the metabolic syndrome. 2. The method of claim 1 , wherein the compound is 4-{2-[3-(5-Hydroxy-adamantan-2-ylcarbamoyl)-phenoxy]-ethyl}-piperidine-1-carboxylic acid isopropylamide or a pharmaceutically acceptable salt thereof.3. The method of claim 1 , wherein the compound is 3-(6-Chloro-pyridin-3-ylmethoxy)-N-(5-hydroxy-adamantan-2-yl)-benzamide or a pharmaceutically acceptable salt thereof.4. The method of claim 1 , wherein the compound is N-(5-Hydroxy-adamantan-2-yl)-3-(tetrahydro-pyran-4-ylmethoxy)-benzamide or a pharmaceutically acceptable salt thereof.5. The method of claim 1 , wherein the compound is N-(5-Hydroxy-adamantan-2-yl)-3-[2-(2-oxo-pyrrolidin-1-yl)-ethoxy]-benzamide or a pharmaceutically acceptable salt thereof.6. The method of claim 1 , wherein the compound is 3-(5-Chloro-pyridin-2-yloxy)-N-(5-hydroxy-adamantan-2-yl)-benzamide or a pharmaceutically acceptable salt thereof.7. The method of claim 1 , wherein the compound is 3-(6-Bromo-pyridin-3-yloxy)-N-(5-hydroxy-adamantan-2-yl)-benzamide or a pharmaceutically acceptable salt thereof.8. The method of claim 1 , wherein the compound is N-(5-Hydroxy-adamantan-2-yl)-3-phenethyloxy-benzamide or a pharmaceutically acceptable salt thereof.9. The method of claim 1 , wherein the compound is N-(5-Hydroxy-adamantan-2-yl)-3-[2-(tetrahydro-pyran-4-yl)-ethoxy]-benzamide or a pharmaceutically acceptable salt thereof.10. The method of claim 1 , wherein the compound is 3-Benzyloxy-N-(5-hydroxy-adamantan-2-yl)-benzamide or a pharmaceutically acceptable ...

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 ...

BETA-LACTAMASE INHIBITORS

Substituted bicyclic beta-lactams of Formula I: 2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein bond a is a single bond and X is —CH— or —CHCH—.3. The compound according to or claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris OSOM.4. The compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Ris OSOH.5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C(O)N(R)R.6. The compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris HetA claim 5 , CH-HetA claim 5 , CHCH-HetA claim 5 , CH(CH)-HetA claim 5 , or CH(CHOH)-HetA.7. The compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein HetA is an optionally fused claim 6 , saturated heterocyclic ring selected from the group consisting of azetidinyl claim 6 , pyrrolidinyl claim 6 , oxopyrrolidinyl claim 6 , piperidinyl claim 6 , piperazinyl claim 6 , tetrahydropyranyl claim 6 , tetrahydrothiopyranyl claim 6 , morpholinyl claim 6 , 1 claim 6 ,1-dioxidotetrahydrothiopyranyl claim 6 , azepanyl claim 6 , oxazepanyl claim 6 , azocanyl claim 6 , and azabicyclo[3.1.0]cyclohexyl claim 6 , wherein the heterocyclic is optionally substituted with 1 or 2 (CH)N(R)Rand optionally substituted with 1 or 2 (CH)R.9. The compound according to claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein T is H claim 8 , CH claim 8 , pyrrolidin-3-yl claim 8 , piperidin-4-yl claim 8 , (CH)OCH claim 8 , (CH)OH claim 8 , (CH)F claim 8 , (CH)-piperidinyl claim 8 , (CH)-pyrrolidinyl; and T′ is H claim 8 , F claim 8 , O—Calkyl claim 8 , OH claim 8 , NH claim 8 , N(H)CH claim 8 , N(CH).10. The compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris HetB.11. The compound according to claim 12 , or a pharmaceutically acceptable salt thereof ...

PROLINAMIADE DERIVATIVES AS THROMBIN INHIBITOR, PREPRARATION METHOD AND APPLICATION THEREOF

Provided are a compound of formula (I), pharmaceutically acceptable salts thereof, preparation methods and applications thereof for inhibiting thrombin, and applications in the treatment and prevention of thrombin-mediated and thrombin-related diseases. 6. The compound of formula (I) claim 1 , pharmaceutically acceptable salt and pharmaceutically acceptable prodrug thereof according to claim 1 , characterized in that the pharmaceutically acceptable salt is selected from the salts derived from pharmaceutically acceptable inorganic acid and organic acid.7. The compound of formula (I) claim 6 , pharmaceutically acceptable salt and pharmaceutically acceptable prodrug thereof according to claim 6 , characterized in that the inorganic acid and organic acid are selected from sulfuric acid claim 6 , sulfurous acid claim 6 , hydrochloric acid claim 6 , acetic acid claim 6 , hydrobromic acid claim 6 , nitric acid claim 6 , phosphoric acid claim 6 , metaphosphoric acid claim 6 , pyrophosphoric acid claim 6 , maleic acid claim 6 , fumaric acid claim 6 , succinic acid claim 6 , citric acid claim 6 , perchloric acid claim 6 , p-toluenesulfonic acid claim 6 , tartaric acid claim 6 , formic acid claim 6 , acetic acid claim 6 , propanoic acid claim 6 , heptylic acid claim 6 , oxalic acid claim 6 , benzoic acid claim 6 , propandioic acid claim 6 , succinic acid claim 6 , succinic acid claim 6 , cis-butenedioic acid claim 6 , hydroxybutanoic acid claim 6 , citric acid claim 6 , methanesulfonic acid claim 6 , benzenesulfonic acid claim 6 , lactic acid or mandelic acid.8. The compound of formula (I) claim 6 , pharmaceutically acceptable salt and pharmaceutically acceptable prodrug thereof according to claim 6 , characterized in that the inorganic acid and organic acid are selected from hydrochloric acid or acetic acid.9. The compound of formula (I) claim 1 , pharmaceutically acceptable salt and pharmaceutically acceptable prodrug thereof according to claim 1 , characterized in that the ...

PROCESS FOR PREPARING CYCLIC AMINE COMPOUNDS

A cyclic amine compound having a prescribed configuration can be efficiently prepared by reducing an imine derivative in the presence of a sulfonic acid. Specifically, a cyclic amine compound which is substituted with an amino group and a carboxyl group in which both groups are arranged in the trans configuration can be prepared efficiently. 2. The process according to claim 1 , wherein Ris Calkyloxy group claim 1 , Calkenyloxy group claim 1 , Caralkyloxy group claim 1 , Caryloxy group claim 1 , Ctrialkylsilyloxy group claim 1 , amino group claim 1 , Calkylamino group claim 1 , Calkenylamino group claim 1 , Caralkylamino group claim 1 , Carylamino group claim 1 , Cdialkylamino group claim 1 , Cdialkenylamino group claim 1 , Cdiaralkylamino group claim 1 , Cdiarylamino group claim 1 , thiol group claim 1 , Calkylthio group claim 1 , Calkenylthio group claim 1 , Caralkylthio group claim 1 , or Carylthio group.3. The process according to claim 1 , wherein the sulfonic acid is sulfuric acid or camphorsulfonic acid; and the reducing agent is borane.4. The process according to claim 1 , wherein Ris benzyloxy group or dibenzylamino group; Ris hydrogen atom; Ris benzyloxy group; and n is 2.5. The process according to claim 4 , further comprising the steps of forming a salt of said cyclic amine compound and oxalic acid claim 4 , and precipitating the salt as a solid in methanol claim 4 , in ethanol claim 4 , in isopropanol claim 4 , in a mixed solvent containing methanol claim 4 , in a mixed solvent containing ethanol claim 4 , or in a mixed solvent containing isopropanol.7. The process according to claim 6 , wherein P is benzyloxycarbonyl group. The present invention relates to a process for producing a cyclic amine compound, specifically, a cyclic amine compound which has an amino group and a carboxyl group as substituents and their configuration is trans, and especially a trans-5-aminopiperidine-2-carboxylic acid derivative, which is useful for an intermediate for ...

C5aR ANTAGONISTS

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

PHENOXYETHYL PIPERIDINE COMPOUNDS

The present invention provides a compound of the Formula II: 2. A compound according to wherein Ris H.3. A compound according to wherein Ris H and Ris methyl.8. A method of treating osteoarthritis in a patient claim 1 , comprising administering to a patient in need of such treatment an effective amount of a compound claim 1 , or pharmaceutically acceptable salt thereof claim 1 , as in .9. A method of treating rheumatoid arthritis in a patient claim 1 , comprising administering to a patient in need of such treatment an effective amount of a compound or pharmaceutically acceptable salt thereof claim 1 , as in .10. A method of treating pain associated with osteoarthritis or rheumatoid arthritis in a patient claim 1 , comprising administering to a patient in need of such treatment an effective amount of a compound or a pharmaceutically acceptable salt thereof claim 1 , as in .11. A pharmaceutical composition claim 1 , comprising a compound or a pharmaceutically acceptable salt thereof as in in combination with one or more pharmaceutically acceptable carriers claim 1 , diluents claim 1 , or excipients.12. The pharmaceutical composition according to claim 11 , further comprising one or more other therapeutic agents. The present invention relates to novel phenoxyethyl piperidine compounds, to pharmaceutical compositions comprising the compounds, to methods of using the compounds to treat physiological disorders, and to intermediates and processes useful in the synthesis of the compounds.The present invention is in the field of treatment of inflammatory conditions, such as arthritis, including osteoarthritis and rheumatoid arthritis, and further including pain associated with these conditions. Arthritis affects millions of patients in the United States alone and is a leading cause of disability. Treatments often include NSAIDs (nonsteroidal anti-inflammatory drugs) or COX-2 inhibitors, which may produce untoward cardiovascular and/or gastrointestinal side effects. As such, ...

PROCESS INTERMEDIATES AND METHODS FOR THE PREPARATION OF PROCESS INTERMEDIATES FOR THE SYNTHESIS OF ARGATROBAN MONOHYDRATE

Methods are provided for the synthesis of key intermediates for the synthesis of Argatroban monohydrate, ethyl (2R,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl. Such intermediates are also provided. 135-. (canceled)36. An ethyl (2R ,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate comprising in an amount HCl between about 1 mol/mol and about 2 mol/mol.37. A solvate of the compound of having an organic solvent or water content of at least 0.5 mol/mol.38. A dihydrochloride form of the compound of having a weight/weight chloride content between about 12 and about 16%.39. A dihydrochloride form of the compound of claim 36 , wherein said compound is solvated by ethanol and has a weight/weight chloride content between about 11 and about 15%.40. A Method for obtaining ethyl (2R claim 36 ,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl claim 36 , solvated or unsolvated claim 36 , comprising exposing a mixture of ethyl (2R claim 36 ,4R)-1-[(2S)-2-amino-5[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate and ethyl (2S claim 36 ,4S)-1-[(2S)-2-amino-5[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl claim 36 , solvated or unsolvated claim 36 , to an organic or aqueous solvent or to a mixture thereof claim 36 , followed by the selective precipitation and isolation of ethyl (2R claim 36 ,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl claim 36 , solvated or unsolvated.41. The method of comprising:a) exposing a mixture of ethyl (2R,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl, solvated or unsolvated, and ethyl (2S,4S)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl] ...

Guanidine compound

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

METHOD FOR PRODUCING 5-HYDROXYPIPERIDINE-2-CARBOXYLIC ACID

A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by the formula (10) below: The present application is a Divisional application of U.S. application Ser. No. 15/108,141, filed Jun. 24, 2016, which is a National Stage of international Patent Application No. PCT/JP2014/084518 filed Dec. 26, 2014, which claims priority to Japanese Application No. 2013-272766 filed Dec. 27, 2013. The disclosures of U.S. application Ser. No. 15/108,141 and International Patent Application No. PCT/JP2014/084518 are incorporated by reference herein in their entireties.The present invention relates to a method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid and synthetic intermediates thereof (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid, which is produced by the method of the present invention, is useful as a synthetic intermediate for a β-lactamase inhibitor and the like.(2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid is a useful intermediate for the synthesis of an agent and the like that inhibits β-lactamases in bacteria exhibiting the resistance against the β-lactam class of antibiotics, which β-lactamases are the major cause of the resistance in the bacteria.A production method using glutamic acid or pyroglutamic acid as a starting raw material has been known as a method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid. Specifically, Patent Document 1 describes that a protected 5-hydroxypiperidine-2-carboxylic acid compound as an intermediate of N-protected oxo-azacycloalkylcarboxylic acids is produced from pyroglutamic acid as a starting raw material through the homologation process to increase carbon atoms and the cyclization process.Moreover, Non-Patent Document 1 describes that a protected 5-hydroxypiperidine-2-carboxylic acid compound is produced from glutamine as a starting raw material through the homologation process to increase carbon atoms and the cyclization process.Non-Patent ...

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) ...

DIAZABICYCLO[4.3.1]DECANE DERIVATIVES FOR TREATMENT OF PSYCHIATRIC DISORDERS

The present invention relates to diazabicyclo[4.3.1]decane derivatives, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said diazabicyclo[4.3.1]decane derivatives can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions. 4. Compound according to selected from the group consisting of:(1S,5S,6R)-5-acetyl-10-((3,5-dichlorophenyl)sulfonyl)-3-(2-methoxyethyl)-3,10-diazabicyclo[4.3.1]decan-2-one,2-((1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-3-(2-methoxyethyl)-2-oxo-3,10-diazabicyclo[4.3.1]decan-5-yl)acetaldehyde,(1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-5-(2-hydroxypropan-2-yl)-3-(2-methoxyethyl)-3,10-diazabicyclo[4.3.1]decan-2-one,(1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-5-((R)-1-hydroxyethyl)-3-(2-methoxyethyl)-3,10-diazabicyclo[4.3.1]decan-2-one,(1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-5-((S)-1-hydroxyethyl)-3-(2-methoxyethyl)-3,10-diazabicyclo[4.3.1]decan-2-one,(1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-5-(2-hydroxyethyl)-3-(2-methoxyethyl)-3,10-diazabicyclo[4.3.1]decan-2-one,(1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-3-(2-methoxyethyl)-2-oxo-3,10-diazabicyclo[4.3.1]decane-5-carbaldehyde,(1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-3-(2-methoxyethyl)-2-oxo-3,10-diazabicyclo[4.3.1]decane-5-carboxylic acid,(1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-3-(2-methoxyethyl)-2-oxo-3,10-diazabicyclo[4.3.1]decane-5-carboxamide,(1S,5R,6R)-10-((3,5-dichlorophenyl)sulfonyl)-3-(2-methoxyethyl)-5-((methylamino)methyl)-3,10-diazabicyclo[4.3.1]decan-2-one,(1S,5R,6R)-10-((3,5-dichlorophenyl)sulfonyl)-5-(hydroxymethyl)-3-(2-methoxyethyl)-3,10-diazabicyclo[4.3.1]decan-2-one,(1S,5R,6R)-10-((3,5-dichlorophenyl)sulfonyl)-3-(2-methoxyethyl)-5-(methoxymethyl)-3,10-diazabicyclo[4.3.1]decan-2-one,(1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-5-ethyl-3-(2- ...

ADO-RESISTANT CYSTEAMINE ANALOGS AND USES THEREOF

The present disclosure is directed to methods for treating diseases for which cysteamine is indicated and compounds useful in such methods. 2. The method of claim 1 , wherein Rand Rare independently selected from the group consisting of H claim 1 , methyl claim 1 , and ethyl.3. The method of claim 1 , wherein Rand R claim 1 , taken together with the nitrogen atom to which they are attached claim 1 , form a 5-membered heterocyclic ring.4. The method of claim 1 , wherein Ris methyl claim 1 , optionally wherein Ris methyl.5. (canceled)6. The method of claim 1 , wherein Rand R claim 1 , taken together with the carbon atom to which they are attached claim 1 , form a 3-membered carbocyclic ring.7. The method of claim 1 , wherein Ris methyl claim 1 , optionally wherein Ris methyl.8. (canceled)9. The method of claim 1 , wherein Rand R claim 1 , taken together with the carbon atom to which they are attached claim 1 , form a 3-membered carbocyclic ring.10. The method of claim 1 , wherein G is —CRRNRR claim 1 , and Rand R claim 1 , taken together with the atoms to which they are attached claim 1 , form a 6-membered heterocyclic ring claim 1 , optionally wherein Ris methyl.11. (canceled)12. The method of claim 1 , wherein G is —NRR claim 1 , and Rand R claim 1 , taken together with the atoms to which they are attached claim 1 , form a 4- or 6-membered heterocyclic ring.13. (canceled)14. (canceled)17. (canceled)18. (canceled)20. The method of wherein L is a 3- claim 19 , 4- claim 19 , 5- claim 19 , 6- claim 19 , 7- claim 19 , or 8-membered cycloalkyl ring or a 6-membered aryl ring.21. The method of wherein L is Calkyl.22. (canceled)23. The method of wherein A is a 3- claim 19 , 4- claim 19 , 5- claim 19 , 6- claim 19 , 7- claim 19 , or 8-membered monocyclic heterocycloalkyl ring claim 19 , a 6- claim 19 , 7- claim 19 , or 8-membered bicyclic heterocycloalkyl ring claim 19 , or a 5- or 6-membered heteroaryl ring.25. (canceled)26. (canceled)27. (canceled)28. (canceled)29. The ...

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 ...

NOVEL IMAGING COMPOSITION AND USES THEREOF

The invention discussed in this application relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. 2. The conjugate of claim 1 , wherein L is OR.3. The conjugate of claim 2 , wherein R is Cto Calkyl.4. The conjugate of claim 2 , wherein OR is selected from O-p-toluenesulfonate claim 2 , O-methanesulfonate claim 2 , O-trifluoromethanesulfonate claim 2 , O-benzenesulfonate claim 2 , and O-m-nitrobenzenesulfonate.5. The conjugate of claim 1 , wherein the target molecule is a polypeptide.6. The conjugate of claim 5 , wherein the polypeptide is an antibody.7. The conjugate of claim 6 , wherein the antibody is selected from trastuzumab claim 6 , rituximab and cetuximab.8. The conjugate of claim 1 , wherein the target molecule is a peptide.9. The conjugate of claim 8 , wherein the peptide is a targeting peptide.10. The conjugate of claim 9 , wherein the targeting peptide is selected from a cyclic RGD sequence claim 9 , bombesin and glu-N(CO)N-lys PSMA. This application is a Continuation of U.S. patent application Ser. No. 15/963,599, filed Apr. 26, 2018, which is a Continuation of U.S. patent application Ser. No. 15/518,333, filed Apr. 11, 2017, now U.S. Pat. No. 9,980,930, issued on May 29, 2018 and is a National Stage Application, filed under 35 U.S.C. 371, of International Application No. PCT/AU2015/050640, filed on Oct. 16, 2015, which claims priority to, and the benefit of, AU Application No. 2014904138, filed Oct. 16, 2014. The contents of each of these applications are incorporated by reference in their entirety.The present invention relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. The present invention also relates to compositions including the compounds, and to methods of imaging patients using the compounds.Zirconium-89 (Zr) is a positron-emitting ...

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- ...

Compounds and uses thereof for the modulation of hemoblogin

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

SOLUBLE C5aR ANTAGONISTS

Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I): 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Ris selected from the group consisting of O—(CO)—Calkylene-NRR claim 1 , O—(CO)—Calkylene-NR(CO)—Calkylene-NRR claim 1 , O—P(O)OROR claim 1 , O—CH—O—P(O)ORORand O—(CO)—Carylene-Calkylene-Cheterocyclyl claim 1 , wherein the Cheterocyclyl is selected from the group consisting of piperidinyl claim 1 , piperazinyl claim 1 , pyrrolidinyl claim 1 , morpholinyl and azetidinyl and wherein the piperidinyl claim 1 , piperazinyl claim 1 , pyrrolidinyl claim 1 , morpholinyl and azetidinyl are optionally substituted with 1 to 6 Rgroups.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of —CH—O—P(O)ORORand —P(O)OROR.12. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of —(CO)—Calkylene- NRR claim 1 , —(CO)—O—Calkylene-O—P(O)OROR claim 1 , —P(O)ORO(CO)—Calkyl claim 1 , —P(O)ORNRR claim 1 , —(CO)—O—Calkylene-O—(CO)—Calkenylene-COH claim 1 , —(CO)—Calkylene-NR(CO)—Calkylene- NRRwherein the Calkylene- NRRmay be optionally substituted by with NRR claim 1 , —(CO)—O—Calkylene-O—(CO)—Calkylene-NRR claim 1 , and —(CO)—O—Calkylene-Caryl-O—P(O)ORORwherein the Caryl is optionally substituted with 1 to 5 Rwhich can be the same or different.15. The compound of any one of to claim 1 , to and to claim 1 , which is in the form of a pharmaceutically acceptable salt.16. The compound of wherein the pharmaceutically acceptable salt is selected from the group consisting of ammonium claim 15 , calcium claim 15 , magnesium claim 15 , potassium claim 15 , sodium claim 15 , zinc claim 15 , arginine claim 15 , betaine claim 15 , caffeine claim 15 , choline claim 15 , N claim 15 ,N′-dibenzylethylenediamine claim 15 , diethylamine claim 15 , 2-diethylaminoethanol claim 15 , 2- ...

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.

PIPECOLATE-DIKETOAMIDES FOR TREATMENT OF PSYCHIATRIC DISORDERS

The present invention relates to compounds having a pipecolate diketoamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said pipecolate diketoamide compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions. 5. Compound according to selected from the group consisting of:2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1S,2R)-1-hydroxy-2-methylcyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid,(S)—((R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl) 1-(2-((1S,2R)-1-hydroxy-2-methylcyclohexyl)-2-oxoacetyl)piperidine-2-carboxylate,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1S,2R)-2-ethyl-1-hydroxy-cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid,(S)—((R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl)1-(2-((1S,2R)-2-ethyl-1-hydroxycyclohexyl)-2-oxoacetyl)piperidine-2-carboxylate,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1S,2S)-1-hydroxy-2-(hydroxyl methyl)cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1R,2R)-1-hydroxy-2-methyl cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1R,2R)-2-ethyl-1-hydroxy cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-(2-cyclohexyl-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy) acetic acid,2-{3-[(1R)-3-(3,4-dimethoxyphenyl)-1-({1-[2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl]piperidin-2-yl}carbonyloxy)propyl]phenoxy}acetic acid,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-oxo-2-(4-phenoxyphenyl)acetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid, and2-(3-((R)-3-(3,4-dimethoxyphenyl)-1 ...

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- ...

INHIBITORS OF THE PD-1/PD-L1 PROTEIN/PROTEIN INTERACTION

The present invention provides novel compounds of formula (I) that are useful as inhibitors of the PD-1/PD-L1 protein/protein interaction. 2. A compound according to claim 1 , wherein Ris a hydrogen atom.3. A compound according to claim 1 , wherein X is CHand Y is O or X is O and Y is CH.4. A compound according to claim 1 , wherein z is a bond claim 1 , CH claim 1 , CH(CH) claim 1 , —CH—NH— or C═O; especially wherein z is CH.5. A compound according to claim 1 , wherein Ris a hydrogen atom claim 1 , a Calkyl group or a heteroalkyl group having from 1 to 6 carbon atoms and from 1 to 5 heteroatoms selected from O claim 1 , S and N (especially O and N).6. A compound according to claim 1 , wherein Ris hydrogen claim 1 , methyl or a group of formula CHCHOH claim 1 , CHCHNHor CHCHNHCOCH.10. A compound according to claim 1 , wherein Aris unsubstituted or wherein Aris substituted by a halogen atom.11. A compound according to claim 1 , wherein Aris substituted by two groups that together are part of a C-Ccycloalkyl group or a heterocycloalkyl group containing 5 or 6 ring atoms selected from O claim 1 , S claim 1 , N and C.12. A compound according to claim 1 , wherein Aris substituted by two groups which together form a group of formula —O—CHCH—O— claim 1 , —O—CH—O— or —O—CF—O—.13. A compound according to claim 1 , wherein Ris methyl or CN.18. A pharmaceutical composition comprising a compound according to or a pharmaceutically acceptable ester claim 1 , prodrug claim 1 , hydrate claim 1 , solvate or salt thereof claim 1 , optionally in combination with a pharmaceutically acceptable carrier.19. Use of a compound or a pharmaceutical composition according to for the preparation of a medicament for the treatment of cancer claim 1 , viral diseases and infectious diseases and neurodegenerative diseases such as: Schizophrenia claim 1 , Alzheimer claim 1 , Multiples Sclerosis claim 1 , Parkinson claim 1 , Corea Huntington claim 1 , Spinocerebellar ataxia type 1 (SCA1) claim 1 , ...

BETA-LACTAMASE INHIBITOR AND PROCESS FOR PREPARING THE SAME

A diazabicyclooctane compound, which is a beta-lactame inhibitor, represented by the following formula (I): 7. The compound of claim 1 , which is selected from the group consisting of(2S,5R)-N-(2-aminoethoxy)-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide,(2S,5R)-N-[2-(methylamino)ethoxy]-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide,(2S,5R)-7-oxo-N-[2-(propan-2-ylamino)ethoxy]-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide,(2S,5R)-N-[2-(dimethylamino)ethoxy]-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide,(2S,5R)-N-{[(2S)-2-aminopropyl]oxy}-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide,(2S,5R)-N-{[(2R)-2-aminopropyl]oxy}-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide,(2S,5R)-N-(3-aminopropoxy)-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide,(2S,5R)-N-[(2S)-azetidin-2-ylmethoxy]-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide,(2S,5R)-7-oxo-N-[(2R)-pyrrolidin-2-ylmethoxy]-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide,(2S,5R)-7-oxo-N-[(2S)-piperidin-2-ylmethoxy]-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide,(2S,5R)-7-oxo-N-[(3S)-pyrrolidin-3-yloxy]-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide and(2S,5R)-N-(azetidin-3-ylmethoxy)-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide, or a pharmaceutically acceptable salt thereof, or a solvate thereof.8. A pharmaceutical composition comprising a pharmaceutically effective amount of the diazabicyclooctane compound represented by the formula (I) of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof claim 1 , and a pharmaceutically acceptable carrier.9. A pharmaceutical composition comprising the compound of and a β-lactam antibiotic claim 1 , in a combined pharmaceutically effective amount claim 1 , and optionally a pharmaceutically acceptable carrier.10. The pharmaceutical composition of claim 8 , for treating a bacterial ...

PROCESSES FOR PREPARING HETEROCYCLIC COMPOUNDS INCLUDING TRANS-7-OXO-6-(SULPHOOXY)-1,6-DIAZABICYCLO[3,2,1]OCTANE-2-CARBOXAMIDE AND SALTS THEREOF

The present invention relates to compounds and processes for preparing compounds of Formula (I), 114-. (canceled)16. The compound of claim 15 , wherein R5 is benzyloxy and R6 and R7 are hydrogen.17. The compound of claim 15 , wherein R5 is allyl or trialkylsilyl and R6 and R7 are hydrogen.18. The compound of claim 15 , wherein R5 is benzyloxy and R1 claim 15 , R2 claim 15 , R6 and R7 are hydrogen.19. The compound of claim 15 , wherein R1 is a heterocycle.20. The compound of claim 15 , wherein R7 is amide.21. The compound of claim 15 , herein R1 is piperidinyl claim 15 , R5 is benzyloxy and R2 claim 15 , R6 and R7 are hydrogen.22. The compound of claim 15 , wherein R1 claim 15 , R2 and R6 are hydrogen.23. The compound of claim 15 , wherein R5 is OSOH.24. The compound of claim 15 , wherein R1 claim 15 , R2 and R6 are hydrogen claim 15 , R5 is OSOH and R7 is carbamoyl.25. The compound of claim 15 , wherein R1 is piperidinyl claim 15 , R2 and R6 are hydrogen claim 15 , R5 is OSOh and R7 is carbamoyl.2644-. (canceled)45. A pharmaceutical composition comprising the compound of or a salt thereof claim 15 , and a pharmaceutical acceptable carrier.48. A pharmaceutical composition comprising the compound of or a salt thereof claim 45 , and a pharmaceutical acceptable carrier. This application claims priority under 35 U.S.C. §119, based on U.S. Provisional Application Ser. No. 61/498,522 filed on Jun. 17, 2011, which is hereby incorporated by reference in its entirety.The present invention relates to novel compounds and processes for preparing compounds of Formula (I), including compounds such as trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and salts thereof (e.g., NXL-104).U.S. Pat. No. 7,112,592 discloses novel heterocyclic compounds and their salts, processes for making the compounds and methods of using the compounds as antibacterial agents. One such compound is sodium salt of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide. ...

Substituted 3-phenylpropylamine derivatives for the treatment of ophthalmic diseases and disorders

The present invention relates generally to compositions and methods for treating neurodegenerative diseases and disorders, particularly ophthalmic diseases and disorders. Provided herein are substituted 3-phenylpropylamine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compositions are useful for treating and preventing ophthalmic diseases and disorders, including age-related macular degeneration (AMD) and Stargardt's Disease.

SUBSTITUTED CYCLIC HYDROXAMATES AS INHIBITORS OF MATRIX METALLOPROTEINASES

The present invention provides compounds of the formula I: 4. A compound according to claim 3 , wherein the compound is of formula III wherein:ring A is a 5-7 membered non-aromatic carbocycle or heterocycle comprising carbon atoms, and from 1-2 ring heteroatoms selected from the group consisting of O, N, NR, provided that ring A contains other than a O—O bond;P is D-Q-L-Y, wherein{'sup': a1', 'a1', 'a1', 'a1', 'a1, 'sub': p', 'p', 'p, 'D is absent or is selected from the group consisting of O, NR, C(O), C(O)NR, NRC(O), S(O), S(O)NR, and NRS(O);'}{'sub': 3-13', 'p, 'sup': b', 'b, 'Q is absent or is selected from the group consisting of a Ccarbocycle substituted with 0-5 R, and a 5-14 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O), and said heterocycle being substituted with 0-5 R;'}{'sup': a1', 'a1', 'a1', 'a1, 'sub': p', 'p', 'p, 'L is absent or is selected from the group consisting of O, NR, C(O), C(O)NR, S(O), S(O)NR, and NRS(O);'}{'sub': 5-7', 'p, 'sup': c', 'c, 'Y is selected from the group consisting of H, a Ccarbocycle substituted with 0-5 Rand a 5-6 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O), and said heterocycle being substituted with 0-5 R;'}{'sub': p', 'p', 'p', 'p, 'provided that D, Q, L and Y do not combine to form a N—N, N—O, O—N, O—O, S(O)—O, O—S(O)or S(O)—S(O)group;'}{'sub': 1-10', '2-10', '2-10', '2', '3', '2', '2', '2', '3', '3', '2', '3', '2', 'r', 'r', 'r', 'r', 'r', 'r', 'r', 'r', 'p', 'r', '2', 'r', '2', 'r', '2', '3-10', 'p, 'sup': b1', 'b1', 'b1', 'd', 'd1', 'a', 'd', 'd1', 'd', 'd1', 'a', 'd', 'd1', 'd', 'd1', 'a', 'd', 'd1', 'a', 'd', 'd1', 'a', 'a1', 'd', 'd1', 'd', 'd1', 'a', 'd', 'd1', 'a', 'd', 'd1', 'a1', 'a2', 'a1', 'a2', 'd', 'd, 'R, at each occurrence, is independently selected from (Calkylene substituted with 1-3 R)-M, (Calkenylene substituted with 1-3 R)-M, (Calkynylene substituted with 1 ...

Apoe4-targeted theraputics that increase sirt1

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

S1P MODULATING AGENTS

Compounds of formula (I) or (II) can modulate the activity of S1P receptors. 132-. (canceled)33. A method for treating stroke in a mammal , comprising administering to said mammal an effective amount of a compound selected from the group consisting of:1-((6-(trans-4-tert-butylcyclohexyloxy)quinazolin-2-yl)methyl)piperidine-4-carboxylic acid;1-(1-(6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)-2,2,2-trifluoroethyl)piperidine-4-carboxylic acid;1-((6-(4-isopropylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(cis-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(4-butylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(spiro[4.5]decan-8-yloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(cis-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(trans-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(trans-4-tert-butylcyclohexyloxy)quinolin-2-yl)methyl)piperidine-4-carboxylic acid;1-(6-(trans-4-tert-butylcyclohexyloxy)-2-naphthoyl)piperidine-4-carboxylic acid;1-((6-((4-tert-butylcyclohexylidene)methyl)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((2-(trans-4-tert-butylcyclohexyloxy)quinolin-6-yl)methyl)piperidine-4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-ethyl-piperidine-4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-propyl-piperidine- 4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-3-methyl-piperidine-4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-phenyl-piperidine-4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-perhydro-azepine-4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2 ...

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 ...

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 ...

THROMBIN INHIBITORS

Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: (I) or a pharmaceutically acceptable salt thereof, wherein Q is CH, NR, O, S, S(O) or S(O), wherein Ris H, Calkyl, aryl, or Ccycloalkyl; Ris a heterocycle or —(CRR)1-2NH2, wherein Rand R, each time in which they occur, are independently H, Calkyl, —CHF, —CHF, CFor —CHOH; Ris OH, NHor NHSOCH; and Ris Calkyl. 3. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris tetrazole or —CHNH.4. A compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Ris —CHNH.5. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris OH.6. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —C(CH).7. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H or CH.8. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.9. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.11. A compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , which is(2S)—N-[2-(aminomethyl)-5-chlorobenzyl]-1-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]piperidine-2-carboxamide,(2S)—N-[2-(aminomethyl)-5-chlorobenzyl]-1-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]piperazine-2-carboxamide,(2S)—N-[2-(aminomethyl)-5-chlorobenzyl]-1-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]-4-methylpiperazine-2-carboxamide,(3 S)—N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]morpholine-3-carboxamide,(3R)—N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]thiomorpholine-3-carboxamide,(3R)—N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]thiomorpholine-3-carboxamide 1-oxide, or(3R)—N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]thiomorpholine-3- ...

INHIBITORS OF HEPATITIS B VIRUS CONVALENTLY CLOSED CIRCULAR DNA FORMATION AND THEIR METHOD OF USE

Pharmaceutical compositions of the invention comprise covalently closed circular DNA formation inhibitors having a disease-modifying action in the treatment of diseases associated with the formation of covalently closed circular DNA that include hepatitis B infection, and any disease involving formation of covalently closed circular DNA. 16. A compound selected from the group consisting of:2-[Benzenesulfonyl-(2-chloro-5-trifluoromethyl-phenyl)-amino]-N-pyridin-4-ylmethyl-acetamide;2-[(2-Chloro-5-trifluoromethyl-phenyl)-(toluene-4-sulfonyl)-amino]-N-pyridin-4-ylmethyl-acetamide;2-[(2-Chloro-5-trifluoromethyl-phenyl)-(4-fluoro-benzenesulfonyl)-amino]-N-pyridin-4-ylmethyl-acetamide;2-(N-(2-chloro-5-(trifluoromethyl)phenyl)phenylsulfonamido)-N-(pyridin-4-ylmethyl)propanamide;4 (N-(2-chloro-5-(trifluoromethyl)phenyl)phenylsulfonamido)-N-(pyridin-4-ylmethyl)butanamide;2-(4-chloro-N-(2-chloro-5-(trifluoromethyl)phenyl)phenylsulfonamido)-N-(pyridin-4-ylmethyl)acetamide;2-(N-(2-chloro-5-(trifluoromethyl)phenyl)-4-methoxyphenylsulfonamido)-N-(pyridin-4-ylmethyl)acetamide;2-(N-(5-chloro-2-fluorophenyl)phenylsulfonamido)-N-(pyridin-4-ylmethyl)acetamide;2-(N-(2-chlor-5-(trifluoromethyl)phenyl)-4-(trifluoromethyl)phenylsulfonamido)-N-(pyridin-4-ylmethyl)acetamide;2-(2-chloro-N-(2-chloro-5-(trifluoromethyl)phenyl)-4-(trifluoromethyl)phenylsulfonamido)-N-(pyridin-4-ylmethyl)acetamide;2-(N-(2-chloro-5-(trifluoromethyl)phenyl)phenyl sulfonamido)-N-(pyridin-3-ylmethyl)acetamide;2-(N-(2-chloro-5-(trifluoromethyl)phenyl)phenyl sulfonamido)-N-(pyrimidin-5-ylmethyl)acetamide;2-(N-(2-chloro-5-(trifluoromethyl)phenyl)phenyl sulfonamido)-N-(pyrimidin-4-ylmethyl)acetamide;N-(2-chloro-5-(trifluoromethyl)phenyl)-N-(2-(3,4-dihydro-2,6-naphthyridin-2(1H)-yl)-2-oxoethyl)benzenesulfonamide;tert-butyl 4-((2-(N-(2-chloro-5-(trifluoromethyl)phenyl)phenylsulfonamido)acetamido)methyl) piperidine-1-carboxylate;tert-butyl (2-(2-(N-(2-chloro-5-(trifluoromethyl)phenyl)phenylsulfonamido)acetamido)ethyl) ...

CYTOTOXIC AND ANTI-MITOTIC COMPOUNDS, AND METHODS OF USING THE SAME

Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity. 4. The compound according to or , wherein each optionally substituted alkyl , optionally substituted alkylamino , optionally substituted cycloalkyl , optionally substituted aryl , optionally substituted heterocyclyl and optionally substituted heteroaryl is , independently , optionally substituted with ═O , ═S , —OH , —OR , —OCR , —SH , —SR , —SOCR , —NH , —N , —NHR , —N(R) , —NHCOR , —NRCOR , —I , —Br , —Cl , —F , —CN , —COH , —COR , —CHO , —COR , —CONH , —CONHR , —CON(R) , —COSH , —COSR , —NO , —SOH , —SORor —SORwherein each Ris , independently , alkyl optionally substituted with halogen , —OH or —SH.5. The compound according to or , wherein each optionally substituted aryl and optionally substituted heteroaryl is , independently , selected from the group consisting of optionally substituted phenyl , optionally substituted naphthyl , optionally substituted anthracyl , optionally substituted phenanthryl , optionally substituted furyl , optionally substituted pyrrolyl , optionally substituted thiophenyl , optionally substituted benzofuryl , optionally substituted benzothiophenyl , optionally substituted quinolinyl , optionally substituted isoquinolinyl , optionally substituted imidazolyl , optionally substituted thiazolyl , optionally substituted oxazolyl , and optionally substituted pyridinyl.128. The composition according to any one of - wherein R claims 2 , R claims 2 , and R claims 2 , are each methyl.138. The composition according to any one of - claims 2 , wherein Ris H claims 2 , Ris methyl claims 2 , and Ris methyl.1413. A pharmaceutical composition ...

SUBSTITUTED 2-HYDROXY-4-(2-(PHENYLSULFONAMIDO)ACETAMIDO)BENZOIC ACID ANALOGS AS INHIBITORS OF STAT PROTEIN

In one aspect, the invention relates to substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. 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. 220.-. (canceled) This application is a continuation application of U.S. application Ser. No. 13/813,916 filed May 10, 2013, while is a national phase application of PCT/US2011/046340 filed Aug. 2, 2011, which claims priority to U.S. Application No. 61/369,796 filed Aug. 2, 2010 and to U.S. Application No. 61/422,046 filed Dec. 10, 2010, each of which is hereby incorporated by reference in its entirety.This invention was made with government support under grant numbers CA106439 and CA128865 awarded by the National Cancer Institute of the National Institutes of Health. The United States government has certain rights in the invention.STAT proteins were originally discovered as latent cytoplasmic transcription factors that mediate cytokine and growth factor responses (Darnell, J. E., Jr. (1996) Recent Prog. Norm. Res. 51, 391-403; Darnell. J. E. (2005) Nat. Med. 11, 595-596). Seven members of the family, STAT1, STAT2, STAT3, STAT4, STAT5a and STAT5b, and STATE, mediate several physiological effects including growth and differentiation, survival, development and inflammation. STATs are SH2 domain-containing proteins. Upon ligand binding to cytokine or growth factor receptors. STATs become phosphorylated on critical Tyr residue (Tyr705 for STAT3) by growth factor receptors, cytoplasmic Janus kinases (Jaks) or Src family kinases. Two phosphorylated ...

S1P MODULATING AGENTS

Compounds of formula (I) or (II) can modulate the activity of S1P receptors. 132-. (canceled)34. The method of claim 33 , wherein the compound is 1-((6-(trans-4-tert-butylcyclohexyloxy)quinazolin-2-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.35. The method of claim 33 , wherein the compound is 1-(1-(6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)-2 claim 33 ,2 claim 33 ,2-trifluoroethyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.36. The method of claim 33 , wherein the compound is 1-((6-(spiro[4.5]decan-8-yloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.37. The method of claim 33 , wherein the compound is 1-((6-(cis-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.38. The method of claim 33 , wherein the compound is 1-((6-(trans-4-tert-butylcyclohexyloxy)quinolin-2-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.39. The method of claim 33 , wherein the compound is 1-(6-(trans-4-tert-butylcyclohexyloxy)-2-naphthoyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.40. The method of claim 33 , wherein the compound is 1-((6-((4-tert-butylcyclohexylidene)methyl)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.41. The method of claim 33 , wherein the compound is 1-((2-(trans-4-tert-butylcyclohexyloxy)quinolin-6-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.42. The method of claim 33 , wherein the compound is 1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-3-methyl-piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.43. The method of claim 33 , wherein the compound is 1-[6-(4-tert-butyl- ...

ASYMMETRIC UREAS AND MEDICAL USES THEREOF

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the ghrelin receptor. The compounds have the general formula (I): 135.-. (canceled)36. A method of agonizing activity of a ghrelin receptor in a human subject comprising administering to said subject an effective amount of a compound selected from the group consisting of 3-(1-(2 ,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1 ,3 ,3-trimethylpiperidin-4-yl)urea , 1-hydroxy-3-(1-(4-methoxynaphthalen-1-yl)ethyl)-1-(1-methylpiperidin-4-yl)urea , and 3-(1-(2 ,3-dichloro-4-methoxyphenyl)ethyl)-1-hydroxy-1-(1-methylpiperidin-4-yl)urea , or a pharmaceutically acceptable salt thereof.37. A method of treating a disease or disorder associated with expression or activity of a ghrelin receptor in a human subject comprising administering to said subject an effective amount of a ghrelin receptor agonist selected from the group consisting of 3-(1-(2 ,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1 ,3 ,3-trimethylpiperidin-4-yl)urea , 1-hydroxy-3-(1-(4-methoxynaphthalen-1-yl)ethyl)-1-(1-methylpiperidin-4-yl)urea , and 3-(1-(2 ,3-dichloro-4-methoxyphenyl)ethyl)-1-hydroxy-1-(1-methylpiperidin-4-yl)urea , or a pharmaceutically acceptable salt thereof.38. The method of claim 37 , wherein said disease or disorder is an eating disorder claim 37 , gastrointestinal disease claim 37 , gastric disorder claim 37 , or cachexia resulting from cancer claim 37 , congestive heart failure claim 37 , wasting due to ageing or AIDS.39. The method of claim 38 , wherein said eating disorder is anorexia nervosa.40. The method of claim 38 , wherein said gastric disorder is selected from the group consisting of Post-operative ileus (POI) claim 38 , diabetic gastroparesis claim 38 , and opioid induced bowel dysfunction.41. The method of claim 38 , wherein said gastrointestinal disease is selected from the group consisting of irritable bowel syndrome claim 38 , ...

ASYMMETRIC UREAS AND MEDICAL USES THEREOF

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the ghrelin receptor. The compounds have the general formula (I): 2. The compound of claim 1 , or a pharmaceutically acceptable salt or adduct thereof claim 1 , wherein R is aryl or heteroaryl.3. The compound of claim 1 , or a pharmaceutically acceptable salt or adduct thereof claim 1 , wherein R is selected from the group consisting of phenyl claim 1 , naphthalene claim 1 , tetrahydronaphthalenyl claim 1 , indenyl claim 1 , isoindenyl claim 1 , indanyl claim 1 , anthracenyl claim 1 , phenanthrenyl claim 1 , benzonaphthenyl claim 1 , fluorenyl claim 1 , indolizinyl claim 1 , pyrindinyl claim 1 , pyranopyrrolyl claim 1 , 4H-quinolizinyl claim 1 , purinyl claim 1 , naphthyridinyl claim 1 , pyridopyridinyl claim 1 , pteridinyl claim 1 , indolyl claim 1 , isoindolyl claim 1 , indoleninyl claim 1 , isoindazolyl claim 1 , benzazinyl claim 1 , phthalazinyl claim 1 , quinoxalinyl claim 1 , quinazolinyl claim 1 , benzodiazinyl claim 1 , benzopyranyl claim 1 , benzothiopyranyl claim 1 , benzoxazolyl claim 1 , indoxazinyl claim 1 , anthranilyl claim 1 , benzodioxolyl claim 1 , benzodioxanyl claim 1 , benzoxadiazolyl claim 1 , benzofuranyl claim 1 , isobenzofuranyl claim 1 , benzothienyl claim 1 , isobenzothienyl claim 1 , benzothiazolyl claim 1 , benzothiadiazolyl claim 1 , benzimidazolyl claim 1 , benzotriazolyl claim 1 , benzoxazinyl claim 1 , benzisoxazinyl claim 1 , and tetrahydroisoquinolinyl claim 1 , which is optionally independently substituted with from one to six substituents independently selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkoxy claim 1 , haloalkyl claim 1 , cyano claim 1 , —NO claim 1 , —OR claim 1 , hydroxy claim 1 , amino claim 1 , alkyl claim 1 , alkenyl claim 1 , cycloalkyl claim 1 , aryl claim 1 , arylalkyl claim 1 , heterocycloalkyl claim 1 , heterocycloalkylalkyl claim 1 , ...

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- ...

COMPOUNDS FOR THE TREATMENT OF DYSLIPIDEMIA AND OTHER DISEASES

The present invention relates to compounds of the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation. The present invention is directed towards compounds which can be used to treat diseases such as hyperlipidemia and also have a beneficial effect on cholesterol. 2. The compound as claimed in wherein A′ is selected from optionally substituted aryl or heteroaryl groups.3. The compound as claimed in wherein when ‘A’ represents and aryl group claim 2 , aryl group is selected from substituted or unsubstituted monocyclic or bicyclic aromatic groups wherein substituents selected from halogen claim 2 , (C-C)alkyl claim 2 , CF claim 2 , OCF claim 2 , OCH claim 2 , SOCHphenyl.4. The compound as claimed in wherein the aryl group is an optionally substituted phenyl group claim 3 , the substituents are selected from (C-C)alkyl claim 3 , CF claim 3 , OCF claim 3 , OCH.5. The compound as claimed in wherein when ‘A’ represents a heteroaryl group claim 2 , the heteroaryl group is selected from single or fused mono claim 2 , bi or tricyclic aromatic groups containing one or more hetero atoms selected from O claim 2 , N or S which optionally substituted with substituents selected from halogen claim 2 , (C-C)alkyl claim 2 , CF claim 2 , OCF claim 2 , OCH claim 2 , SOCHphenyl group further optionally substituted with CH claim 2 , CF claim 2 , OCHor halogen.6. The compound as claimed in wherein the heteroaryl group is selected from pyridyl claim 5 , thienyl claim 5 , furyl claim 5 , pyrrolyl claim 5 , oxazolyl claim 5 , thiazolyl claim 5 , isothiazolyl claim 5 , imidazolyl claim 5 , isoxazolyl claim 5 , oxadiazolyl claim 5 , thiadiazolyl claim 5 , triazolyl claim 5 , tetrazolyl claim 5 , benzofuranyl claim 5 , benzothienyl claim 5 , indolinyl claim 5 , indolyl claim 5 , ...

Substituted 1,1'-biphenyl compounds, analogues thereof, and methods using same

The present invention includes substituted 3,3′bis(phenoxymethyl)-1,1′-biphenyl compounds, analogues thereof, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) and/or hepatitis D virus (HDV) infections in a patient.

TRANS-ISOMERIC HETEROCYCLIC COMPOUNDS AND PREPARATION THEREOF

A trans-isomeric compound of formula (I) below or a pharmaceutically acceptable salt thereof: 2. The compound of claim 1 , wherein Ris C-Calkyl.3. The compound of claim 2 , wherein Ris methyl.8. The method of claim b claim 2 , wherein Ris C-Calkyl.9. The method of claim 8 , wherein Ris methyl.10. The method of claim 6 , wherein the palladium catalyst is Pd(OH)/C claim 6 , Pd/C claim 6 , Pd(OAc) claim 6 , Pd/AlO claim 6 , or a combination thereof claim 6 , optionally containing Pt/C or Rh/C; and the content of palladium in the palladium catalyst is 0.01 wt % to 30 wt %.11. The method of claim 6 , wherein the inert solvent is HO claim 6 , a C-Cester claim 6 , a C-Ccycloalkane claim 6 , tetrahydrofuran (THF) claim 6 , dimethylformamide (DMF) claim 6 , acetonitrile claim 6 , a C-Calcohol claim 6 , an alkylene glycol monoalkyl ether claim 6 , an alkylene glycol monoalkyl ether carboxylate claim 6 , an amide-based solvent claim 6 , an organic acid claim 6 , or a combination thereof claim 6 , optionally combined with one or more inorganic acids.12. The method of claim 11 , wherein the inert solvent is HO claim 11 , a C-Cester claim 11 , a C-Ccycloalkane claim 11 , THF claim 11 , DMF claim 11 , a C-Calcohol claim 11 , propylene glycol monomethyl ether claim 11 , propylene glycol monomethyl ether acetate claim 11 , N claim 11 ,N-dimethylacetamide claim 11 , a C-Ccarboxylic acid claim 11 , a C-Csulfonic acid claim 11 , or a combination thereof claim 11 , optionally combined with hydrochloric acid.13. The method of claim 12 , wherein the inert solvent is HO claim 12 , methanol claim 12 , ethanol claim 12 , isopropanol claim 12 , formic acid claim 12 , acetic acid claim 12 , ethyl acetate claim 12 , methanesulfonic acid claim 12 , or a combination thereof claim 12 , optionally combined with hydrochloric acid.14. The method of claim 11 , wherein the inert solvent is an organic acid or a combination of the organic acid with one or more solvents selected from the group consisting ...

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 ...

PROCESSES FOR PREPARING A DIAZABICYCLOOCTANE COMPOUND

A process for preparing a diazabicyclooctane compound represented by the following formula (I): This application is a Divisional application of U.S. application Ser. No. 15/973,861, filed May 8, 2018, which is a Divisional application of U.S. application Ser. No. 15/583,238, filed May 1, 2017 (now U.S. Pat. No. 10,023,573), which is a Divisional application of U.S. application Ser. No. 14/872,988, filed Oct. 1, 2015 (now U.S. Pat. No. 9,708,320), which is a Divisional application of U.S. application Ser. No. 14/404,288, filed Nov. 26, 2014 (now U.S. Pat. No. 9,181,250), which is a U.S. National Stage application of International Application No. PCT/JP2013/064971, filed May 30, 2013, which claims priority of Japanese Application No. 2012-122603, filed May 30, 2012, the entire contents of all of which are incorporated by reference herein.The present invention relates to a novel diazabicyclooctane derivative represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof. The present invention also relates to a process for preparing the same, and a use thereof as a β-lactamase inhibitor for the treatment of bacterial infection. The present invention further relates to a pharmaceutical composition and a method of treating bacterial infection using the compound of the present invention.Penicillins and cephalosporins are β-lactam antibiotics which are most widely and frequently used in the clinic. However, the acquisition of resistance to β-lactam antibiotics by various pathogens severely has had a damaging effect on maintaining the effective treatment of bacterial infections. The most significant known mechanism related to the acquisition of bacterial resistance is the production of class A, C, and D β-lactamases having a serine residue at the active center. These enzymes decompose the β-lactam antibiotic, resulting in the loss of the antimicrobial activities. Class A β-lactamases preferentially hydrolyze penicillins while class C β- ...

Substituted piperidines as sodium channel blockers

The present disclosure provides substituted piperidines or pyrrolidines having Formula IA: and the pharmaceutically acceptable salts and solvates thereof, wherein R 1 , R 2a , R 2b , R 6 , A, X, m and n are defined as set forth in the specification. In certain embodiments, Compounds of the present disclosure are useful for treating pain. The present disclosure is also directed to the use of Compounds of the present disclosure to treat a disorder responsive to blockade of one or more sodium channels.

Cycloalkyl Amine Compounds

Cycloalkyl amine compounds of Formula (I), 2. The compound of claim 1 , wherein Rand Rare both H claim 1 , and R claim 1 , R claim 1 , Rand Rare all H.3. (canceled)5. The compound of claim 4 , wherein Ris H.7. (canceled)9. The compound of claim 1 , wherein ring A is unsubstituted.10. The compound of claim 1 , wherein ring A is substituted with one or more C-Calkyl.11. The compound of claim 10 , wherein ring A is substituted with one C-Calkyl.12. The compound of claim 1 , wherein ring A is optionally substituted C-Ccycloalkyl.13. The compound of claim 12 , wherein the compound is of Formula (Ia) or (Ib) and ring A is unsubstituted cyclobutyl.14. The compound of claim 12 , wherein the compound is of Formula (Ic) and ring A is unsubstituted cyclopentyl.15. The compound of claim 12 , wherein the compound is of Formula (Ic) and ring A is optionally substituted cyclobutyl.16. The compound of claim 2 , wherein each of Rand R claim 2 , independently claim 2 , is H claim 2 , halo claim 2 , or cyano.17. The compound of claim 16 , wherein at least one of Rand Ris halo.18. The compound of claim 17 , wherein each of Rand Ris chloro.19. The compound of claim 16 , wherein Rand R claim 16 , together with the carbon atoms to which they are attached claim 16 , form phenyl claim 16 , pyridyl claim 16 , pyrrolyl claim 16 , furanyl claim 16 , thienyl claim 16 , thiazolyl claim 16 , oxazolyl claim 16 , imidazolyl claim 16 , pyrazolyl claim 16 , isoxazolyl claim 16 , triazolyl claim 16 , oxadiazolyl claim 16 , pyridazinyl claim 16 , pyrazinyl claim 16 , or pyrimidyl.20. The compound of claim 2 , wherein one of Rand Ris H and the other is C-Calkyl optionally substituted with halo or is C-Ccycloalkyl optionally substituted with C-Calkyl.21. The compound of claim 20 , wherein the other of Rand Ris isopropyl or t-butyl claim 20 , optionally substituted with one or more halo groups.22. The compound of claim 1 , wherein one of Rand Ris C-Calkyl optionally substituted with halo and the other is ...

Methods of preparing hydroxylamine derivatives useful in the preparation of anti-infective agents

The present invention relates to processes for the preparation of N-protected 4-((2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxamido)piperidine-1-carboxylates. Such compounds have application in the preparation of beta-lactamase inhibitors such as 7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamides and esters, in particular, the beta lactamase inhibitor, (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. The present invention also encompasses intermediates useful in the disclosed processes and methods for their preparation.

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.

NIPECOTIC ACID DERIVATIVE AND USE THEREOF FOR MEDICAL PURPOSES

A compound has an sEH-inhibiting activity and provides a pharmaceutical having a therapeutic effect and a prophylactic effect on chronic renal disease and pulmonary hypertension based on the sEH-inhibiting action. The nipecotic acid derivatives are represented by the chemical formula below and pharmaceutically acceptable salts thereof. 16.-. (canceled)8. The nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to claim 7 , wherein{'sup': 2', '3', '2', '3, 'sub': 1', '6', '2', 'l, 'Rand Reach independently represents a hydrogen atom or C-Calkyl, or together represent —(CH)—, with the proviso that Rand Rdo not simultaneously represent a hydrogen atom;'}{'sup': '4', 'Rrepresents a substituent in the 2-position of the benzene ring; and'}{'sup': '5', 'Rrepresents a substituent in the 4-position of the benzene ring.'}9. The nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to claim 7 , wherein{'sup': 1', '6', '7', '6', '7, 'sub': '2', 'Rrepresents —N(R)C(═O)Ror —N(R)S(═O)R;'}{'sup': '4', 'sub': 1', '6, 'Rrepresents a halogen atom, or C-Calkyl or alkyloxy;'}{'sup': '5', 'sub': 1', '6, 'Rrepresents a halogen atom, cyano, or C-Calkyl or alkyloxy; and'}{'sup': '6', 'Rrepresents a hydrogen atom.'}10. A pharmaceutical comprising as an effective component the nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to .11. A soluble epoxide hydrolase inhibitor comprising as an effective component the nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to .12. A therapeutic or prophylactic agent for chronic renal disease or pulmonary hypertension claim 7 , said agent comprising as an effective component the nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to .13. The nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to claim 8 , wherein{'sup': 1', '6', '7', '6', '7, 'sub': '2', 'Rrepresents —N(R)C(═O) ...

C5aR ANTAGONISTS

Compounds are provided that are modulators of the C5a receptor. The compounds are substituted piperidines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activtation of C5a receptors. 2. The compound of claim 1 , wherein X is hydrogen.35-. (cancelled)1015-. (cancelled)16. The compound of claim 1 , wherein Cis selected from the group consisting of phenyl claim 1 , pyridyl claim 1 , indolyl and thiazolyl claim 1 , each of which is optionally substituted with from 1 to 3 Rsubstituents.17. The compound of claim 1 , wherein Cis selected from the group consisting of phenyl claim 1 , naphthyl claim 1 , pyridyl and indolyl claim 1 , each of which is optionally substituted with from 1 to 3 Rsubstituents.18. The compound of claim 1 , wherein Cis selected from the group consisting of Calkyl claim 1 , Ccycloalkyl claim 1 , CcycloalkylCalkyl claim 1 , phenyl claim 1 , pyridinyl claim 1 , pyrazolyl claim 1 , piperidinyl claim 1 , pyrrolidinyl claim 1 , piperidinylmethyl and pyrrolidinylmethyl claim 1 , each of which is optionally substituted with from 1 to 3 Rsubstituents.1923-. (cancelled)2526-. (cancelled)30. The method of claim 28 , wherein the disease or disorder is an inflammatory disease or disorder.31. The method of claim 30 , wherein the disease or disorder is selected from the group consisting of neutropenia claim 30 , sepsis claim 30 , septic shock claim 30 , Alzheimer's disease claim 30 , multiple sclerosis claim 30 , stroke claim 30 , inflammatory bowel disease claim 30 , chronic obstructive pulmonary disorder claim 30 , inflammation associated with burns claim 30 , lung injury claim 30 , osteoarthritis claim 30 , atopic dermatitis claim 30 , chronic urticaria claim 30 , ischemia-reperfusion injury claim 30 , acute respiratory distress syndrome claim 30 , systemic inflammatory response syndrome claim 30 , multiple organ dysfunction syndrome claim 30 , tissue graft rejection and hyperacute ...

C5aR ANTAGONISTS

Compounds are provided that are modulators of the C5a receptor. The compounds are substituted piperidines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activation of C5a receptors. 2. The compound of claim 1 , wherein X is hydrogen.15-. (canceled)812-. (canceled)1415-. (canceled)16. The compound of claim 1 , wherein Cis selected from the group consisting of phenyl claim 1 , pyridyl claim 1 , indolyl and thiazolyl claim 1 , each of which is optionally substituted with from 1 to 3 Rsubstituents.17. The compound of claim 1 , wherein Cis selected from the group consisting of phenyl claim 1 , naphthyl claim 1 , pyridyl and indolyl claim 1 , each of which is optionally substituted with from 1 to 3 Rsubstituents.18. The compound of claim 1 , wherein Cis selected from the group consisting of Calkyl claim 1 , Ccycloalkyl claim 1 , CcycloalkylCalkyl claim 1 , phenyl claim 1 , pyridinyl claim 1 , pyrazolyl claim 1 , piperidinyl claim 1 , pyrrolidinyl claim 1 , piperidinylmethyl and pyrrolidinylmethyl claim 1 , each of which is optionally substituted with from 1 to 3 Rsubstituents.1929-. (canceled)31. A method for treating a mammal suffering from or susceptible to a disease or disorder involving pathologic activation of C5a receptors claim 1 , comprising administering to the mammal an effective amount of a compound of .32. A method of inhibiting C5a receptor-mediated cellular chemotaxis comprising contacting mammalian white blood cells with a C5a receptor modulatory amount of a compound of .33. The method of claim 31 , wherein the disease or disorder is an inflammatory disease or disorder.34. The method of claim 33 , wherein the disease or disorder is selected from the group consisting of neutropenia claim 33 , sepsis claim 33 , septic shock claim 33 , Alzheimer's disease claim 33 , multiple sclerosis claim 33 , stroke claim 33 , inflammatory bowel disease claim 33 , age-related macular degeneration ...

SUBSTITUTED ASYMMETRIC UREAS AS MODULATORS OF GHRELIN RECEPTOR ACTIVITY

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the ghrelin receptor. The compounds have the general Formula I: 261-. (canceled) The present invention relates to novel asymmetric urea compounds, medical uses thereof, particularly in the treatment of medical conditions modulated by the ghrelin receptor.The growth hormone secretagogue receptor (GHS-R) regulates a number of physiological processes, including growth hormone (GH) release, metabolism, and appetite. Ghrelin, a circulating hormone produced predominantly by endocrine cells in the stomach, is its endogenous ligand. Ghrelin is a 28 amino acid peptide with an acyl side chain required for biological activity (Kojima et al., Nature, 402, 656-660, 1999). Ghrelin has been shown to stimulate growth hormone (GH) release and to increase food intake when administered both centrally and peripherally (Wren et al., Endocrinology, 141, 4325-4328, 2000).Endogenous levels of ghrelin rise on fasting and fall on re-feeding in humans (Cummings et al., Diabetes, 50, 1714-1719, 2001). Ghrelin also appears to play a role in maintaining long term energy balance and appetite regulation. Chronic administration of ghrelin in rodents leads to hyperphagia and weight gain that are independent of growth hormone secretion (Tschop et al., Nature, 407, 908-913, 2000). Circulating ghrelin levels decrease in response to chronic overfeeding and increase in response to chronic negative energy balance associated with anorexia or exercise. Obese people generally have low plasma ghrelin levels (Tschop et al., Diabetes, 50, 707-709, 2001) accordingly to the physiological response of the body in reducing calories intake. Intravenous ghrelin is effective in stimulating food intake in humans. A recent study showed a 28% food intake increase from a buffet meal with a ghrelin infusion compared with saline control (Wren et al., J. Clin. Endocrinology and ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 181-. (canceled)83. The compound of claim 82 , wherein Ris Pand Ris H.84. The compound of claim 82 , wherein Ris H and Ris P.85. The compound of claim 82 , wherein Ris Pand Ris P.88. The compound of claim 82 , wherein each of Rto Ris H.89. The compound of claim 82 , wherein at least one of Rto Ris deuterium.90. The compound of claim 82 , wherein Z is —OH claim 82 , —OR claim 82 , —N(R)Ror P.91. The compound of claim 82 , wherein Z is P.92. The compound of claim 82 , wherein Z is —OH.93. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or excipients.94. The pharmaceutical composition of claim 93 , which is formulated for transdermal delivery claim 93 , optionally via a patch.95. A method of treating pulmonary hypertension claim 82 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.96. The method of claim 95 , wherein the pulmonary hypertension is pulmonary arterial hypertension.97. The method of claim 95 , wherein the compound is administered orally claim 95 , topically or parenterally.98. The method of claim 97 , wherein the compound is administered transdermally claim 97 , optionally via a patch.99. The method of claim 95 , further comprising administering an additional therapeutic agent.100. The method of claim 99 , wherein the additional therapeutic agent is selected from the group consisting of vasoactive agents claim 99 , diuretics claim 99 , anticoagulants and cardiac glycosides. This application is ...

IMMUNE CHECKPOINT INHIBITORS, COMPOSITIONS AND METHODS THEREOF

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis aryl.3. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis aryl optionally substituted by halogen claim 1 , (C-C)alkyl or (C-C)haloalkyl.4. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis NH(R) or N(R)(R).5. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris (C-C)alkyl or halogen.6. The compound of claim 5 , or a stereoisomer claim 5 , a tautomer or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris CH.7. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare independently H claim 1 , (C-C)alkyl or Rand Rcombine together with the nitrogen atom to form a heterocyclyl.8. The compound of claim 7 , or a stereoisomer claim 7 , a tautomer or a pharmaceutically acceptable salt thereof claim 7 , wherein Rand Rare independently H or (C-C)alkyl claim 7 , wherein (C-C)alkyl is optionally substituted by OH or C(O)OH.9. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rcombine together with the nitrogen atom to form a heterocyclyl claim 1 , optionally substituted by C(O)OH.10. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein “n” is 1.11. A compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable ...

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

Inhibitors of HBV replication of formula (I) 112-. (canceled)16. The compound of claim 13 , wherein each of Ra claim 13 , Rb claim 13 , Rc claim 13 , Rd claim 13 , Re claim 13 , Rf claim 13 , Rg claim 13 , Rh and Ri is hydrogen.17. The compound of claim 13 , wherein at least one of Ra claim 13 , Rb claim 13 , Rc claim 13 , Rd claim 13 , Re claim 13 , Rf and Rg is methyl.18. The compound of claim 13 , wherein Ris fluoro.19. The compound of claim 13 , wherein Ris selected from the group consisting of fluoro claim 13 , chloro claim 13 , —CHF claim 13 , —CHF claim 13 , —CF claim 13 , —CN and methyl.20. The compound of claim 13 , wherein Ris selected from the group consisting of fluoro claim 13 , chloro and bromo.21. The compound of claim 13 , wherein Ris fluoro; Ris selected from the group consisting of fluoro claim 13 , chloro claim 13 , —CHF claim 13 , —CHF claim 13 , —CF claim 13 , —CN and methyl; and Ris selected from the group consisting of fluoro claim 13 , chloro and bromo.22. The compound of claim 13 , wherein Ris fluoro and Ris methyl.23. The compound of claim 13 , wherein Ris fluoro; Ris selected from the group consisting of fluoro and chloro; and Ris selected from the group consisting of hydrogen claim 13 , fluoro and chloro.24. The compound of claim 13 , wherein Ris a branched C-Calkyl optionally substituted with one or more fluoro.25. The compound of claim 13 , wherein Ris selected from the group consisting of —CH(CH) claim 13 , —CH(CH) claim 13 , —CH(CH) claim 13 , —(CH)(CH)CH claim 13 , —(CH)(CH)CH—OH claim 13 , —CH(CH)CF claim 13 , CH(CH)CF.26. The compound of claim 13 , wherein Ris —CH(CH).27. The compound of claim 13 , wherein Ris —CH(CH)CF.28. The compound of claim 13 , wherein Ris fluoro; and Ris —CH(CH)CF.29. The compound of claim 13 , wherein Ris a 4-5 membered saturated ring containing one oxygen claim 13 , said 4-5 membered saturated ring optionally substituted with methyl.30. A pharmaceutical composition comprising the compound of and a ...

ESTER SUBSTITUTED ION CHANNEL BLOCKERS AND METHODS FOR USE

The invention provides compounds of Formula (I), or pharmaceutically acceptable salts thereof: 2. The compound of claim 1 , wherein Ris methyl or ethyl.3. The compound of claim 1 , wherein Xis —NHC(O)—.4. The compound of claim 1 , wherein Ris methyl claim 1 , and Ris selected from the group consisting of hydrogen claim 1 , methyl claim 1 , halogen claim 1 , nitrile claim 1 , methoxy claim 1 , and ethoxy.5. The compound of claim 1 , wherein Rare methyl and Ris hydrogen.6. The compound of claim 1 , wherein each of Rand Ris independently selected from hydrogen claim 1 , D claim 1 , substituted or unsubstituted alkyl; or Rand Rtogether form a substituted or unsubstituted C-Ccycloalkyl or substituted or unsubstituted heterocyclic.7. The compound of claim 6 , wherein Rand Rare both hydrogen.8. The compound of claim 6 , wherein Ris hydrogen and Ris a C-Calkyl.9. The compound of claim 8 , wherein Ris hydrogen and Ris methyl claim 8 , ethyl claim 8 , n-propyl claim 8 , or n-butyl.10. The compound of claim 6 , wherein Rand Rare taken together with the carbon to which they are attached to form a substituted or unsubstituted C-Ccycloalkyl.11. The compound of claim 1 , wherein each of R claim 1 , Rand Ris the same or different and is selected from a substituted or unsubstituted alkyl claim 1 , a substituted or unsubstituted aryl claim 1 , or a substituted or unsubstituted heteroaryl.12. The compound of claim 11 , wherein each of R claim 11 , Rand Ris the same.13. The compound of claim 1 , wherein Rand Rare the same or different and are each independently a substituted or unsubstituted alkyl claim 1 , and Ris a substituted or unsubstituted arylalkyl claim 1 , or a substituted or unsubstituted heteroarylalkyl.15. The compound of claim 1 , wherein two of R claim 1 , Rand Rtogether with the N to which they are attached form an optionally substituted 5- to 10-membered heterocyclic ring having claim 1 , zero claim 1 , one claim 1 , or more heteroatoms in addition to the N.16. The ...

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Chemical entities that are curcumin derivatives, pharmaceutical compositions and methods of treatment of cancer are described. 2. At least one chemical entity of wherein Ris chosen from hydrogen claim 1 , optionally substituted alkyl claim 1 , optionally substituted cycloalkyl claim 1 , and optionally substituted heterocycloalkyl.3. At least one chemical entity of wherein Ris chosen from optionally substituted alkyl claim 1 , optionally substituted cycloalkyl claim 1 , and optionally substituted heterocycloalkyl.4. At least one chemical entity of wherein Rand Rare independently chosen from optionally substituted alkyl.5. At least one chemical entity of wherein Rand Rare joined together to form an optionally substituted 4- to 8-membered heterocycloalkyl ring.6. At least one chemical entity of wherein Rand Rare joined together to form an optionally substituted pyrrolidin-1-yl claim 5 , morpholin-1-yl claim 5 , piperidin-1-yl claim 5 , piperazin-1-yl claim 5 , 1 claim 5 ,4-diazepan-1-yl claim 5 , and 1 claim 5 ,4-diazocan-1-yl.7. At least one chemical entity of any one of to wherein Ris chosen from hydrogen claim 5 , optionally substituted alkyl claim 5 , optionally substituted cycloalkyl claim 5 , optionally substituted heterocycloalkyl claim 5 , optionally substituted aryl claim 5 , optionally substituted heteroaryl claim 5 , optionally substituted aminocarbonyl claim 5 , and optionally substituted phosphato.8. At least one chemical entity of wherein Ris chosen from hydrogen claim 7 , optionally substituted lower alkyl claim 7 , and optionally substituted aminocarbonyl.9. At least one chemical entity of wherein Ris hydrogen.10. At least one chemical entity of wherein Ris optionally substituted lower alkyl.11. At least one chemical entity of wherein Ris methyl.12. At least one chemical entity of wherein Ris lower alkyl substituted with hydroxyl or amino.13. At least one chemical entity of wherein Ris optionally substituted aminocarbonyl.14. At least one chemical ...

SELECTIVE FKBP51 LIGANDS FOR TREATMENT OF PSYCHIATRIC DISORDERS

The present invention relates to compounds having a selective FKBP51 ligand scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said selective FKBP51 ligand compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions. 4. The compound according to selected from the group consisting of:2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-(((S)-1-((S)-2-(3,4,5-trimethoxyphenyl)pent-4-enoyl)pyrrolidine-2-carbonyl)oxy)propyl)phenoxy)acetic acid,A09 (S)-(R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl-1-((S)-3-cyclopropyl-2-(3,4,5-trimethoxyphenyl)propanoyl)pyrrolidine-2-carboxylate,A15 (S)-(R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl-1-((S)-2-((R)-cyclohex-2-en-1-yl)-2-(3,4,5-trimethoxyphenyl)acetyl)pyrrolidine-2-carboxylate, andA21 (S)-(R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl-1-((S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl) acetyl)pyrrol-idine-2-carboxylate,5. A method for inhibiting a FK506-binding protein comprising contacting a cell with an effective amount of a compound according to .6. A method for treating a disease comprising administering a therapeutically effective amount of a compound according to to a subject in need thereof claim 1 , wherein the disease is selected from a psychiatric disorder claim 1 , a neurological disorder claim 1 , a metabolic disease claim 1 , cancer claim 1 , a glucocorticoid hyposensitivity syndrome claim 1 , peripheral glucocorticoid resistance claim 1 , an infectious disease claim 1 , alopecia claim 1 , abnormally elevated intraocular pressure claim 1 , macular degeneration claim 1 , oxidative damage to eye tissues claim 1 , vision disorder claim 1 , a sleeping disorder claim 1 , asthma claim 1 , diabetes claim 1 , traumatic brain injury claim 1 , ...

PROCESSES AND INTERMEDIATES IN THE PREPARATION OF C5aR ANTAGONISTS

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds. 18.-. (canceled).10. A compound of claim 9 , in salt form as a L-DTTA salt.11. A compound of claim 9 , wherein Ris CF.12. A compound of claim 9 , wherein Ris Cl.13. A compound of claim 9 , in salt form as a bis L-DTTA salt.15. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris F claim 14 , and Ris CH.16. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris Cl claim 14 , and Ris H.17. A method in accordance with claim 14 , wherein Ris Cl claim 14 , Ris F claim 14 , and Ris CH.18. A method in accordance with claim 14 , wherein LG is halogen.1920.-. (canceled). This application is a continuation of U.S. patent application Ser. No. 14/867,669 filed Sep. 28, 2015, which application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/057,107, filed Sep. 29, 2014, each of which is incorporated herein by reference.NOT APPLICABLEThe complement system plays a central role in the clearance of immune complexes and in immune responses to infectious agents, foreign antigens, virus infected cells and tumor cells. Inappropriate or excessive activation of the complement system can lead to harmful, and even potentially life-threatening consequences due to severe inflammation and resulting tissue destruction. These consequences are clinically manifested in various disorders including septic shock; myocardial, as well as, intestinal ischemia/reperfusion injury; graft rejection; organ failure; nephritis; pathological inflammation; and autoimmune diseases.The activation of the complement pathway generates biologically active fragments of complement proteins, e.g. C3a, C4a and C5a anaphylatoxins and C5b-9 membrane attack complexes (MAC), all which mediate inflammatory responses by affecting leukocyte chemotaxis; activating macrophages, neutrophils, platelets, mast cells and endothelial cells; and increasing vascular permeability, ...

INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the disclosure. 2. The compound of claim 1 , wherein X is CH.3. The compound of claim 1 , wherein X is N.4. The compound of claim 1 , wherein Ris H.5. The compound of claim 1 , wherein Ris Calkyl.6. The compound of claim 1 , wherein Ris H.7. The compound of claim 1 , wherein Ris Calkyl.8. The compound of claim 1 , wherein Ris Calk-OCalkyl.9. The compound of claim 1 , wherein Ris H.10. The compound of claim 1 , wherein Ris Calkyl.11. The compound of claim 1 , wherein Ris phenyl optionally substituted with one claim 1 , two or three substituents independently selected from halogen claim 1 , Calk-O—Calkyl claim 1 , or —CN.12. The compound of claim 11 , wherein Ris 4-chlorophenyl claim 11 , 4-chloro-2-fluorophenyl claim 11 , 4-chloro-3-fluorophenyl claim 11 , 3-fluoro-4-methoxyphenyl claim 11 , 2-fluoro-4-methoxyphenyl claim 11 , or 4-cyano-3-methoxyphenyl.13. The compound of claim 1 , wherein Ris heteroaryl optionally substituted with one claim 1 , two or three substituents independently selected from halogen claim 1 , optionally substituted phenyl claim 1 , optionally substituted benzyl claim 1 , optionally substituted Calkyl claim 1 , Chaloalkyl claim 1 , Calk-O—Calkyl claim 1 , heterocyclyl claim 1 , and —CN.14. The compound of claim 13 , wherein Ris 1H-pyrazol-4-yl claim 13 , thiazol-2-yl claim 13 , furan-3-yl claim 13 , benzo[d][1 claim 13 ,3]dioxol-5-yl claim 13 , 2 claim 13 ,3-dihydrobenzofuran-5-yl claim 13 , benzofuran-5-yl claim 13 , benzo[b]thiophen-5-yl claim 13 , pyrimidin-5-yl claim 13 , 1H-indazol-4-yl claim 13 , 1H-pyrrolo[2 claim 13 ,3-c]pyridin-3-yl claim 13 , benzo[d]thiazol-2-yl claim 13 , imidazo[1 claim 13 ,2-a]pyridin-2-yl claim 13 , benzo[c][ ...

Anti-viral compounds

Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

Lipids and lipid compositions for the delivery of active agents

or a pharmaceutically acceptable salt thereof, wherein R1-R4, L1, n and p are defined herein. The compounds of formula (X) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues.

THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF

The invention provides compounds having the general Formula (I); 2. The method of claim 1 , wherein Ris F or Cl; and Ris selected from the group consisting of F claim 1 , Cl claim 1 , Calkyl claim 1 , Calkoxy claim 1 , and Ccycloalkyl.3. The method of claim 1 , wherein Ris F or Cl and Ris selected from the group consisting of F claim 1 , Cl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , and cyclopentyl.4. The method of claim 1 , wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is an optionally substituted Calkylene.5. The method of claim 1 , wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)CH)—CH— claim 1 , or —CHCHCHCH—.6. The method of claim 1 , wherein Xis —O—; the subscript m is 1 and -(L)- is —CH— claim 1 , —C(H)(CH)— claim 1 , or —CH—CH—.7. The method of claim 1 , wherein Xis absent; Xis —O— or —N(H)—; the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)(CH)—CH— claim 1 , or —CHCHCHCH—.8. The method of claim 1 , wherein Xand Xare absent; the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)(CH)—CH— claim 1 , or —CHCHCHCH—.9. The method of claim 1 , wherein Xand Xare absent: the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , and —CH—CH—.10. The method of claim 1 , wherein m is 0; Xis selected from —O— and —N(H)—; and Xis absent. This application is a divisional of U.S. application Ser. No. 16/150,070, filed 2 Oct. 2018 ...

PROCESS FOR PRODUCING HETEROCYCLIC COMPOUND

The present invention provides a method of efficiently producing an optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative. The optically active piperidine-3-carboxamide or a derivative thereof, which is obtained by subjecting 1,4,5,6-tetrahydropyridine-3-carboxamide or a derivative thereof to an asymmetric reduction in the presence of a catalyst, is used as an intermediate. 2. The method according to claim 1 , wherein the organic metal complex is a transition metal complex.3. The method according to claim 2 , wherein the transition metal complex is a ruthenium complex.4. The method according to claim 3 , wherein the ruthenium complex is represented by the formula:{'br': None, 'sup': 'a', 'sub': '2', '[Ru(OCOR)L*]\u2003\u2003(VIII)'}wherein{'sup': 'a', 'sub': '1-3', 'Ris an optionally substituted Calkyl group; and'}{'sup': 'a', 'Lis a diphosphine ligand.'} This application is a divisional of U.S. application Ser. No. 15/125,299, which is the U.S. National Stage application of PCT/JP2015/057541, filed Mar. 13, 2015, which claims priority from Japanese application 2014-052809, filed Mar. 14, 2014.The present invention relates to a production method of an optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative which is useful as a dipeptidylpeptidase inhibitor, and various intermediates useful therefor, and production methods thereof.An optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative is known to be useful as a dipeptidylpeptidase inhibitor and an agent for the treatment of diabetes.Patent Document 1 discloses a method of producing a 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative by reacting optically active 3-aminopiperidine with a 6-chloro-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative.Patent Document 2 discloses a method of efficiently producing an optically active 8-(3-aminopiperidin-1-yl)xanthine derivative by ...

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 4. (canceled)7. The compound of claim 2 , wherein ring B is substituted with 1-3: halo claim 2 , C-Calkyl claim 2 , COR claim 2 , or COOR; and{'sup': '15', 'sub': 1', '6', '6', '10', '1', '6', '6', '10, 'Ris C-Calkyl, C-Caryl, 5-10 membered heteroaryl or a 4-10 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N, S, and oxidized forms of N and S, wherein the C-Calkyl, C-Caryl, 5-10 membered heteroaryl or 4-10 membered heterocyclyl is optionally substituted.'}8. (canceled)10. A composition comprising a compound of and at least one pharmaceutically acceptable excipient.11. A method for increasing oxygen affinity of hemoglobin S in a subject claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .12. A method for treating oxygen deficiency associated with sickle cell anemia or acute respiratory distress syndrome claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .13. A composition comprising a compound of and at least one pharmaceutically acceptable excipient.14. A method for increasing oxygen affinity of hemoglobin S in a subject claim 9 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .15. A method for treating oxygen deficiency associated with sickle cell anemia or acute respiratory distress syndrome claim 9 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .16. A method for increasing oxygen affinity of hemoglobin S in a ...

FREE BASE CRYSTALLINE FORM OF A COMPLEMENT COMPONENT C5a RECEPTOR

Provided herein is a free base crystalline form of a complement component 5a receptor having the formula of Compound 1 12.-. (canceled)3. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by XRPD peaks at 12.4 claim 11 , 15.2 claim 11 , 16.1 claim 11 , 24.4 claim 11 , and 24.7 degrees 2θ (±0.2 degrees 2θ)4. The method of claim 11 , wherein the free base crystalline form of Compound 1 is characterized by an X-ray powder diffraction pattern substantially in accordance with .5. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a differential scanning calorimetry thermogram (DSC) comprising an endothermic peak at around 216° C.6. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a melting point onset of about 213° C. as determined by differential scanning calorimetry thermogram (DSC).7. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a DSC substantially in accordance with .810.-. (canceled)12. The method of claim 11 , wherein the disease or disorder is an inflammatory disease or disorder.13. The method of claim 12 , wherein the disease or disorder is selected from the group consisting of neutropenia claim 12 , sepsis claim 12 , septic shock claim 12 , Alzheimer's disease claim 12 , multiple sclerosis claim 12 , stroke claim 12 , inflammatory bowel disease claim 12 , age-related macular degeneration claim 12 , chronic obstructive pulmonary disorder claim 12 , inflammation associated with burns claim 12 , lung injury claim 12 , osteoarthritis claim 12 , atopic dermatitis claim 12 , chronic urticaria claim 12 , ischemia-reperfusion injury claim 12 , acute respiratory distress syndrome claim 12 , systemic inflammatory response syndrome claim 12 , multiple organ dysfunction syndrome claim 12 , tissue graft rejection claim 12 , cancer and hyperacute ...

PROCESS FOR PRODUCING HETEROCYCLIC COMPOUND

The present invention provides a method of efficiently producing an optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative. 2. The method according to claim 1 , wherein the organic metal complex is a transition metal complex.3. The method according to claim 2 , wherein the transition metal complex is a ruthenium complex.4. The method according to claim 3 , wherein the ruthenium complex is represented by the formula:{'br': None, 'sup': a', 'a, 'sub': '2', '[Ru(OCOR)L]\u2003\u2003(VIII)'}wherein{'sup': 'a', 'sub': '1-3', 'Ris an optionally substituted Calkyl group; and'}{'sup': 'a', 'Lis a diphosphine ligand.'} The present invention relates to a production method of an optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative which is useful as a dipeptidylpeptidase inhibitor, and various intermediates useful therefor, and production methods thereof.An optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative is known to be useful as a dipeptidylpeptidase inhibitor and an agent for the treatment of diabetes.Patent Document 1 discloses a method of producing a 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative by reacting optically active 3-aminopiperidine with a 6-chloro-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative.Patent Document 2 discloses a method of efficiently producing an optically active 8-(3-aminopiperidin-1-yl)xanthine derivative by subjecting racemic 3-aminopiperidine to acylation with phthalic anhydride, subjecting the obtained 3-phthalimide piperidine to optical resolution with optically active tartaric acid, coupling the obtained optically resolved compound with a xanthine ring, and subjecting the obtained compound to deacylation.Patent Document 3 discloses a method of optically resolving racemic piperidine-3-carboxamide with optically active lactic acid.Patent Document 4 discloses a method of producing an optically ...

PIPERIDINE/PIPERAZINE DERIVATIVES

The invention relates to a DGAT inhibitor of formula 3. The compound as claimed in or wherein X represents —O—C(═O)—; —NR—C(═O)—; —Z—C(═O)—; —Z—NR—C(═O)—; —NR—C(═S)—.4. The compound as claimed in wherein X represents —NR—C(═O)— or —Z—C(═O)—.5. The compound as claimed in any one of the preceding claims wherein A represents N.6. The compound as claimed in any one of the preceding claims wherein Rrepresents arylor Het.7. The compound as claimed in wherein Rrepresents optionally substituted phenyl claim 6 , optionally substituted fluorenyl or an optionally substituted monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from O claim 6 , S claim 6 , S(═O)or N.8. The compound as claimed in any one of the preceding claims wherein Rrepresents Ccycloalkyl claim 6 , phenyl claim 6 , 2 claim 6 ,3-dihydro-1 claim 6 ,4-benzodioxinyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms claim 6 , wherein said phenyl or heterocycle are optionally substituted with one to four substituents.9. The compound as claimed in any one of the preceding claims wherein Y represents —C(═O)—NR— or —NR—C(═O)—.12. The compound as claimed in or wherein Rand Reach independently represent halo or Calkyl.13. The compound as claimed in any one of the preceding claims wherein Rrepresents hydrogen.14. The compound as claimed in wherein X represents —O—C(═O)—; —NR—C(═O)—; —Z—C(═O)—; —Z—NR—C(═O)—; —NR—C(═S)—; Z represents Calkanediyl; Rrepresents hydrogen; Y represents —C(═O)—NR— or —NR—C(═O)—; Rrepresents arylor Het; Rrepresents Ccycloalkyl claim 1 , phenyl claim 1 , 2 claim 1 ,3-dihydro-1 claim 1 ,4-benzodioxinyl claim 1 , or a 6-membered aromatic heterocycle containing 1 or 2 N atoms claim 1 , wherein said Ccycloalkyl claim 1 , phenyl claim 1 , 2 claim 1 ,3-dihydro-1 claim 1 ,4-benzodioxinyl claim 1 , or heterocycle may optionally be substituted with one to four substituents claim 1 , each substituent independently selected from halo; ...

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 2. (canceled)3. The compound of claim 1 ,{'sub': 2', '2', '2, 'wherein Y—Z is —CHO— or —CHCH—.'}4. The compound of claim 3 , wherein Ris C-Calkoxy.6. (canceled)7. The compound of claim 1 , wherein ring B is substituted with 1-3substituents selected from halo claim 1 , C-Calkyl claim 1 , COR claim 1 , and COOR; and{'sup': '15', 'sub': 1', '6', '6', '10, 'Ris C-Calkyl, C-Caryl, 5-10 membered heteroaryl or a 4-10 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N, S, and oxidized forms of N and S, wherein the alkyl, aryl, heteroaryl or heterocyclyl is optionally substituted.'}8. (canceled)9. (canceled)10. A composition comprising a compound of claim 1 , and at least one pharmaceutically acceptable excipient.11. A method for increasing oxygen affinity of hemoglobin S in a subject claim 1 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .12. A method for treating sickle cell disease claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of . This application is a continuation of U.S. application Ser. No. 15/688,185, filed Aug. 28, 2017, which is a continuation of U.S. application Ser. No. 14/836,869, filed Aug. 26, 2015, now U.S. Pat. No. 9,776,960, which is a continuation of U.S. application Ser. No. 14/599,341, filed Jan. 16, 2015, which is a continuation of U.S. application Ser. No. 13/815,735, filed Mar. 15, 2013, now U.S. Pat. No. 8,952,171, which are incorporated herein by reference in their entirety.This invention provides compounds and pharmaceutical compositions ...

INSOLUBLE COMPLEX OR SOLVATE THEREOF, PHARMACEUTICAL COMPOSTION AND USE THEREOF

The present invention provides a complex of formula (I) or a solvate thereof (wherein n is 1 to 4), a pharmaceutical composition, and use of the pharmaceutical composition in the prevention or treatment of surgical pain, intraoperative pain and postsurgical pain. The technical solution according to the present invention provides a medicament which can be produced by a simple production process and can stably release a local anesthetic in body for a long period. The medicament can be released for at least three days or more, which can prolong the analgesic effect on the postsurgical pain, can be used conveniently by the physician and the patient, and has a good treatment compliance. 2. The complex or the solvate thereof according to claim 1 , wherein n is 2.3. The complex or the solvate thereof according to claim 2 , wherein the solvate is a methanol solvate claim 2 , an ethanol solvate claim 2 , or a hydrate.4. The complex or the solvate thereof according to claim 2 , wherein the complex or the solvate is an ethanol solvate having a polymorph A claim 2 , wherein an X-ray powder diffraction pattern thereof claim 2 , measured with Cu—Kα radiation claim 2 , has diffraction peaks at about 4.9±0.2 claim 2 , 9.8±0.2 claim 2 , and 12.0±0.2 represented by 2θ.5. The complex or the solvate thereof according to claim 4 , wherein the X-ray powder diffraction pattern of the polymorph A is substantially as shown in .6. The complex or the solvate thereof according to claim 2 , wherein the complex or the solvate thereof is a methanol solvate having a polymorph B claim 2 , wherein an X-ray powder diffraction pattern thereof claim 2 , measured with Cu—Kα radiation claim 2 , has diffraction peaks at about 10.9±0.2 claim 2 , 12.6±0.2 claim 2 , and 13.7±0.2 represented by 2θ.7. The complex or the solvate thereof according to claim 6 , wherein the X-ray powder diffraction pattern of the polymorph B is substantially as shown in .8. The complex or the solvate thereof according to claim 2 , ...

FACTOR XIIa INHIBITORS

This invention relates to compounds of formula (I). The compounds of formula (I) are modulators of Factor XII, specifically Factor XIIa. The compounds are inhibitors of Factor XIIa and may be useful as anticoagulants. The compounds of formula (I) may be used in methods of treatment (or prevention) of blood disorders related to bleeding or coagulation. 3. The compound of any preceding claim wherein L is selected from bond , —O— , or —C(O)O—.4. The compound of any preceding claim , wherein Ris H and/or Ris H and/or Ris H.5. The compound of any preceding claim wherein Ris selected from substituted or unsubstituted: phenyl or a 5 or 6 membered heterocycloalkyl ring system.6. The compound of any preceding claim wherein Ar is selected from phenyl , 6 membered heteroaryl or 9 to 10 membered bicyclic heteroaromatic ring system (preferably 9 membered) , wherein Ar is unsubstituted or substituted with Calkyl , —OR , —NRRor Calkyl substituted by —NRR. Optionally , Ar is unsubstituted or substituted with methyl , chloro , —OMe , —NHor —CHNH.8. The compound of wherein Ar is azaindole claim 6 , benzotriazole or N-methyl benzotriazole.9. The compound of any preceding claim wherein Ris H claim 6 , Me or —C(O)Me.10. The compound of any preceding claim wherein -L-(CRR)— is selected from: a bond claim 6 , CH claim 6 , —NH— claim 6 , —NHCH— claim 6 , —NH(CH)— claim 6 , —NH(CH)— claim 6 , —N(Me)- claim 6 , —N(C(O)Me)CH— claim 6 , —NHC(O)— claim 6 , —NHC(O)CH— claim 6 , —NHC(O)(CH)— claim 6 , or NHC(O)(CH)—.11. The compound of any preceding claim wherein Ris selected from: ═CH claim 6 , —CN claim 6 , halo claim 6 , Calkyl claim 6 , Chaloalkyl claim 6 , —OR claim 6 , —NRR claim 6 , phenyl or napthalenyl claim 6 , cyclopropyl claim 6 , cyclobutyl claim 6 , cyclopentyl claim 6 , cyclohexyl claim 6 , tetrahydropyranyl claim 6 , tetrahydrofuranyl claim 6 , piperidinyl claim 6 , piperazinyl claim 6 , morpholinyl claim 6 , pyrrolidinyl claim 6 , pyrazolidinyl claim 6 , imidazolidinyl claim 6 , ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 147-. (canceled)49. The compound of claim 48 , wherein R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , and Rare H.50. The compound of claim 48 , wherein at least one of R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , and Rare is deuterium.51. The compound of claim 48 , wherein Lis —O-alkylene-C(O)—.52. The compound of claim 48 , wherein Lis —O-alkylene-OC(O)—.53. The compound of claim 48 , wherein Lis a bond.54. The compound of claim 48 , wherein the alkylene group is a C-Calkylene group.55. The compound of claim 48 , wherein the alkylene group is a Calkylene group.56. (canceled)5863-. (canceled)66. A composition comprising a compound of claim 48 , or and one or more pharmaceutically acceptable excipients.67. The composition of claim 66 , which is formulated for transdermal delivery.6870-. (canceled)71. A method of treating pulmonary hypertension claim 66 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of claim 66 , or or a pharmaceutically acceptable salt thereof.72. The method of claim 71 , wherein the pulmonary hypertension is pulmonary arterial hypertension.73. The method of claim 71 , wherein the compound is administered transdermally. This application claims priority to U.S. provisional application 61/751,608 filed Jan. 11, 2013 ...

PROCESSES AND INTERMEDIATES IN THE PREPARATION OF C5aR ANTAGONISTS

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds. 2. A compound of claim 1 , in salt form as a bis L-DTTA salt.6. A method of any of claim 1 , or claim 1 , wherein Ris CF claim 1 , Ris F claim 1 , and Ris CH.7. A method of any of claim 1 , or claim 1 , wherein Ris CF claim 1 , Ris Cl claim 1 , and Ris H.8. A method of any of claim 1 , or claim 1 , wherein Ris Cl claim 1 , Ris F claim 1 , and Ris CH.10. A compound of claim 9 , in salt form as a L-DTTA salt.11. A compound of claim 9 , wherein Ris CF.12. A compound of claim 9 , wherein Ris Cl.13. A compound of claim 9 , in salt form as a bis L-DTTA salt.15. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris F claim 14 , and Ris CH.16. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris Cl claim 14 , and Ris H.17. A method in accordance with claim 14 , wherein Ris Cl claim 14 , Ris F claim 14 , and Ris CH.18. A method in accordance with claim 14 , wherein LG is halogen. This application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/057,107, filed Sep. 29, 2014, the entire content of which is incorporated herein by reference.NOT APPLICABLENOT APPLICABLEThe complement system plays a central role in the clearance of immune complexes and in immune responses to infectious agents, foreign antigens, virus infected cells and tumor cells. Inappropriate or excessive activation of the complement system can lead to harmful, and even potentially life-threatening consequences due to severe inflammation and resulting tissue destruction. These consequences are clinically manifested in various disorders including septic shock; myocardial, as well as, intestinal ischemia/reperfusion injury; graft rejection; organ failure; nephritis; pathological inflammation; and autoimmune diseases.The activation of the complement pathway generates biologically active fragments of complement proteins, e.g. C3a, C4a and C5a anaphylatoxins and ...

Quaternary ammonium salt compound, preparation method therefor and use thereof

A quaternary ammonium salt compound of formula I is fast-acting and has a long-term local anaesthetic effect after a single administration, the sensory nerve block time being longer than the motor nerve block time, has both a long-acting local anaesthetic effect and a selective local anaesthetic effect, and also significantly reduces the side effects of quaternary ammonium salt compounds with the structural features of surfactants and is highly safe; thus, the compound of formula I and the pharmaceutically acceptable salt thereof can be used for the preparation of saft drugs having a long-term local anaesthetic effect and a selective local anaesthetic effect

Autotaxin inhibitors

The present invention relates to novel compounds that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in the treatment of an ATX-dependent or ATX-mediated disease or condition. 7. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.8. A pharmaceutical combination comprising a therapeutically effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and one or more therapeutically active co-agent.9. A method of treating a disease or condition selected from fibrosis claim 1 , pruritus claim 1 , cirrhosis claim 1 , cancer claim 1 , diabetes claim 1 , kidney diseases claim 1 , pain claim 1 , asthma and COPD comprising administering to the subject a therapeutically effective amount of a compound according to .10. The method according to claim 9 , wherein the disease or condition is idiopathic pulmonary fibrosis or pruritus. The present invention relates to novel compounds that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in diseases and disorders mediated by autotaxin.Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase (ENPP2), is a secreted ectoenzyme known to possess lysophospholipase D activity (Umezu-Goto et al., 2002), and is responsible for producing the bioactive lipid mediator lysophosphatidic acid (LPA) by the hydrolysis of lysophosphatidylcholine (LPC) (Tokumura et al., 2002). LPA is highly implicated in the pathogenesis of a number of physio-pathological diseases, including cancer (Liu et al., 2009; Mills & Moolenaar, 2003), neuropathic pain (Inoue et al., 2004) and fibrosis (Tager et al., 2008). Following the production of LPA, the lipid binds to specific G protein-coupled receptors of ...

Methods and Compositions for the Synthesis of Multimerizing Agents

The invention features methods and compositions for the synthesis of multimerizing agents. An exemplary method for producing AP20187 may comprise: (a) coupling 2-N,Ndimethylaminomethyl-1,3-diaminopropane with AP20792 to produce the dimeric alcohol, AP20793; and (b) coupling the AP20793 so produced with API7362 to yield AP20187. In particular embodiments, the method further includes the step of producing API7362 by coupling API7360 with methyl-L-pipecolic acid, or a salt thereof. 6. The method of wherein the base is lithium bis(trimethylsilyl)amide.9. The method of in which the reducing agent is LiAlH.13. The method of which further comprises the step of producing 2-N claim 8 ,N-dimethylaminomethyl-1 claim 8 ,3-diaminopropane by the method of .14. The method of which further comprises the step of producing 2-N claim 8 ,N-dimethylaminomethyl-1 claim 8 ,3-diaminopropane by the method of .16. A method for producing AP20187 by:(a) coupling 2-N,N-dimethylaminomethyl-1,3-diaminopropane with AP20792 to produce the dimeric alcohol, AP20793; and(b) coupling the AP20793 so produced with AP17362 to yield AP20187.17. A method for producing AP20187 by:(a) reacting 3-bromo-2-bromomethyl-N,N-dimethylpropylamine or the quaternary salt thereof with diformylamine to produce 2-N,N-dimethylaminomethyl-1,3-diaminopropane;(b) coupling 2-N,N-dimethylaminomethyl-1,3-diaminopropane with AP20792 to produce the dimeric alcohol, AP20793; and(c) coupling the AP20793 so produced with AP17362 to yield AP20187.18. The method of which further includes the step of producing AP17362 by coupling AP17360 with methyl-L-pipecolic acid claim 16 , or a salt thereof.19. The method of which further includes the step of producing AP17362 by coupling AP17360 with methyl-L-pipecolic acid claim 17 , or a salt thereof.2019. The method of any of - which further comprises recovering the compound so produced claims 5 , or a salt thereof claims 5 , from the reaction mixture. The present invention relates to methods ...

PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY ENRICHED 3-AMINOPIPERIDINE

The present invention relates to a process for the preparation of enantiomerically enriched 3-aminopiperidine, as in particular of its R-enantiomer (R)-3-aminopiperidine. The invention also relates to an enantiomerically enriched intermediate of said process and to specific acid-addition salts of 3-aminopiperidine (hereinafter also APIP) that are useful for obtaining a single enantiomer of APIP, and to crystalline (R)-3-aminopiperidine-dihydrochloride-monohydrateand crystalline (S)-3-aminopiperidine-dihydrochloride-monohydrate. 2. The process according to claim 1 , wherein the carboxylic acid A is selected from (S)-2-phenyl sulfonylamino-propionic acid claim 1 , (S)-2-(4-methylphenyl)sulfonylamino-propionic acid claim 1 , (S)-2-(4-chlorophenyl)sulfonylamino-propionic acid claim 1 , (R)-2-(3-phenylureido)-propionic acid and (R)-2-(3-(4-chlorophenyl)ureido)-propionic acid.3. A process for enantiomeric enrichment of 3-aminopiperidine with regard to its S-enantiomer claim 1 , the process comprising the fractional crystallization of 3-aminopiperidine in the form of its acid-addition salt with a chiral carboxylic acid A from a solution claim 1 , suspension or emulsion containing a mixture of the enantiomers of 3-aminopiperidine claim 1 , in particular a racemic mixture of the enantiomers of 3-aminopiperidine claim 1 ,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'where the chiral carboxylic acid A is the compound of the formula A, as defined in , where the chiral carboxylic acid A has an enantiomeric excess with regard to one of its enantiomers.'}4. The process according to claim 3 , wherein the carboxylic acid A is selected from (R)-2-phenyl sulfonylamino-propionic acid claim 3 , (R)-2-(4-methylphenyl)sulfonylamino-propionic acid claim 3 , (R)-2-(4-chlorophenyl)sulfonylamino-propionic acid claim 3 , (S)-2-(3-phenylureido)-propionic acid and (S)-2-(3-(4-chlorophenyl)ureido)-propionic acid.5. The acid-addition salt of 3-aminopiperidine with the chiral carboxylic acid A ...

SUBSTITUTED BENZAMIDES AND METHODS OF USE THEREOF

The invention provides compounds having the general formula I: 24-. (canceled)713-. (canceled)14. The compound of claim 1 , wherein Ris Ccycloalkyl.1517-. (canceled)18. The compound of claim 1 , wherein Xis —O—; the subscript m is 1 and -(L)- is —CH— or —CH—CH—.19. The compound of claim 1 , wherein Xis absent; Xis —O— or —N(H)—; the subscript m is 1; and -(L)- is selected from the group consisting of —C(H)— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)(CH)—CH— or —CHCHCHCH—.20. The compound of claim 1 , wherein Xand Xis absent; the subscript m is 1; and -(L)- is selected from the group consisting of —C(H)— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)(CH)—CH— or —CHCHCHCH—.2122-. (canceled)2530-. (canceled)3236-. (canceled)38. The compound of wherein Ris methyl claim 37 , ethyl claim 37 , cyclopropyl claim 37 , or 1-azetidinyl.39. The compound of claim 37 , wherein —X-(L)-X— is —O— claim 37 , —CH— claim 37 , —CH—O— claim 37 , or —CHCH—O—.42. The compound of claim 37 , wherein A is optionally substituted azetidine claim 37 , pyrrolidine claim 37 , piperidine claim 37 , morpholine claim 37 , homopiperazine claim 37 , and piperazine.4344-. (canceled)4749-. (canceled)51. (canceled)52. A method of treating a disease or condition in a mammal selected from the group consisting of pain claim 1 , depression claim 1 , cardiovascular diseases claim 1 , respiratory diseases claim 1 , and psychiatric diseases claim 1 , and combinations thereof claim 1 , wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound of formula I as described in claim 1 , or a pharmaceutically acceptable salt thereof.5364-. (canceled) The present invention relates to organic compounds useful for therapy and/or prophylaxis in a mammal, and in ...

PHARMACEUTICAL COMBINATION OF AN EP4 ANTAGONIST AND IMMUNE CHECKPOINT INHIBITORS FOR THE TREATMENT OF TUMOURS

The present invention provides a pharmaceutical combination comprising the EP4 antagonist of Formula (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)-benzoic acid or a pharmaceutically acceptable salt thereof and at least one immune checkpoint inhibitor, preferably the sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl) benzoic acid. A polymorphic form A of sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl) benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)benzoate characterized by a powder XRD spectrum with peaks at values of the angle 2θ+0.2° of 4.3, 5.0, 5.8, 6.4, 7.1, 8.3, 8.7, 12.8, 15.3, 15.9 is also described. The combination and the polymorphic form A are described for use in the treatment of tumours. 113-. (canceled)14. A pharmaceutical combination comprising the EP4 antagonist of Formula (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)-benzoic acid or a pharmaceutically acceptable salt thereof and at least one immune checkpoint inhibitor.15. The pharmaceutical combination according to claim 14 , wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride claim 14 , sodium salt claim 14 , potassium salt claim 14 , and lithium salt.16. The pharmaceutical combination according to claim 14 , wherein the EP4 antagonist is sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)benzoic acid.17. A polymorphic form A of sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)benzoic acid characterized by a powder XRD spectrum with peaks at values of the angle 2θ±0.2° of 4.3 claim 14 , 5.0 claim 14 , 5.8 claim 14 , 6.4 claim 14 , 7.1 claim 14 , 8.3 claim 14 , 8.7 claim 14 , 12.8 claim 14 , 15.3 claim 14 , 15.9.18. The polymorphic form A according to for use as a medicament.19. The polymorphic form A ...

ANDROGEN RECEPTOR MODULATOR COMPOUNDS AND METHODS

Provided herein are compounds having a structure selected from among Formula (I), Formula (II), Formula (III), Formula (IV), Formula (V) and Formula (VI) that are androgen receptor modulators and/or androgen receptor binding agents. Also disclosed are methods of making and using such compounds, including, but not limited to, using such compounds for treating various conditions. 2. The method of claim 1 , wherein the androgen receptor is in a cell.3. The method of claim 1 , wherein the compound is an androgen receptor agonist.4. The method of claim 1 , wherein the compound is an androgen receptor antagonist.5. The method of claim 1 , wherein the compound is a compound of Formula II claim 1 , or a pharmaceutically acceptable salt claim 1 , ester claim 1 , amide or prodrug thereof.6. The method of claim 1 , wherein the compound is selected from:N,N-bis(2,2,2-trifluoroethyl)-3-methyl-4-nitroaniline;N,N-bis(2,2,2-trifluoroethyl)-4-nitroaniline;4-Bromo-N,N-bis(2,2,2-trifluoroethyl)-3-(trifluoromethyl)aniline;4-(Bis(2,2,2-trifluoroethyl)amino)-2-(trifluoromethyl)benzonitrile;(5R)—N-(4-nitrophenyl)-5-(dimethyl-tort-butylsilyloxymethyl)-2-pyrrolidone;(5R)—N-(4-nitrophenyl)-5-(hydroxymethyl)-2-pyrrolidone;(2R)—N-(4-nitro-3-trifluoromethylphenyl)-2-(dimethyl-tert-butylsilyloxymethyl)pyrrolidine;(2R)—N-(4-nitro-3-trifluoromethylphenyl)-2-(hydroxymethyl)pyrrolidine;(2R)—N-(4-nitrophenyl)-2-(hydroxymethyl)pyrrolidine;(2R)—N-(3-Trifluoromethyl-4-nitrophenyl)-2-formylpyrrolidine;(2R)—N-(3-Trifluoromethyl-4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine;(2R)—N-(3-Trifluoromethyl-4-nitrophenyl)-2-(1-(R)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine;(2S)—N-(4-nitrophenyl)-2-(hydroxymethyl)pyrrolidine;(2R)—N-(4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine;(2R)—N-(4-nitrophenyl)-2-(R)-(1-(R)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine;(2S)—N-(4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl);(2S)—N-(4-nitrophenyl)-2-(1-(R)-hydroxy-2,2,2-trifluoroethyl) ...

Glutamine Transport Inhibitors and Methods for Treating Cancer

The present disclosure provides compounds of formula: 13. The compound of claim 11 , wherein Rand Rare C claim 11 , CH claim 11 , CH claim 11 , or NH claim 11 , and form a ring.15. The compound of claim 14 , wherein: Xand X claim 14 , Xand X claim 14 , or Xand Xjoin together to form pyrazole claim 14 , pyrrole claim 14 , pyridine claim 14 , pyrrolidine claim 14 , piperidine claim 14 , phenyl claim 14 , cyclohexane claim 14 , cyclopentene claim 14 , tetrahydropyran claim 14 , pyran claim 14 , furan claim 14 , dioxolane claim 14 , dioxane claim 14 , oxazole claim 14 , imidazole claim 14 , thiophene claim 14 , oxathiolane claim 14 , dioxepane claim 14 , or dioxepine.17. A pharmaceutical composition claim 1 , comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.18. A method of treating cancer in a subject in need thereof claim 1 , the method comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to the subject.19. A method of treating cancer in a subject in need thereof claim 5 , the method comprising administering a therapeutically effective amount of a compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , to the subject.20. A method of treating cancer in a subject in need thereof claim 14 , the method comprising administering a therapeutically effective amount of a compound of claim 14 , or a pharmaceutically acceptable salt thereof claim 14 , to the subject. This invention was made with government support under grant numbers P30CA068485, P50CA095103, and P30DK058404 awarded by the National Institutes of Health. The government has certain rights in the invention.Healthy mammalian cells sequester the amino acid glutamine through an evolutionarily redundant family of cell-surface transporters known as the solute carrier family of proteins (SLC). The alanine-serine-cysteine ...

NOVEL IMAGING COMPOSITION AND USES THEREOF

The invention discussed in this application relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. 115-. (canceled)17. The conjugate of claim 16 , wherein L is OR.18. The conjugate of claim 17 , wherein R is Cto Calkyl.19. The conjugate of claim 17 , wherein OR is selected from O-p-toluenesulfonate claim 17 , O-methanesulfonate claim 17 , O-trifluoromethanesulfonate claim 17 , O-benzenesulfonate claim 17 , and O-m-nitrobenzenesulfonate.20. The conjugate of claim 16 , wherein the target molecule is a polypeptide.21. The conjugate of claim 20 , wherein the polypeptide is an antibody.22. The conjugate of claim 21 , wherein the antibody is selected from trastuzumab claim 21 , rituximab and cetuximab.23. The conjugate of claim 16 , wherein the target molecule is a peptide.24. The conjugate of claim 23 , wherein the peptide is a targeting peptide.25. The conjugate of claim 24 , wherein the targeting peptide is selected from a cyclic RGD sequence claim 24 , bombesin and glu-N(CO)N-lys PSMA. The present invention relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. The present invention also relates to compositions including the compounds, and to methods of imaging patients using the compounds.Zirconium-89 (Zr) is a positron-emitting radionuclide that is used in medical imaging applications. In particular, it is used in positron emission tomography (PET) for cancer detection and imaging. It has a longer half-life (t=79.3 hours) than other radionuclides used for medical imaging, such as F. For example, F has a tof 110 minutes, which means that its use requires close proximity to a cyclotron facility and rapid and high-yielding synthesis techniques for the preparation of the agents into which it is incorporated. Zr is not plagued by these same problems, which makes ...

PROCESSES FOR PREPARING HETEROCYCLIC COMPOUNDS INCLUDING TRANS-7-OXO-6-(SULPHOOXY)-1,6-DIAZABICYCLO[3,2,1]OCTANE-2-CARBOXAMIDE AND SALTS THEREOF

The present invention relates to compounds and processes for preparing compounds of Formula (I), 2. The process of claim 1 , wherein R1 claim 1 , R2 and R7 are hydrogen and R3 is OSOH.3. The process of claim 1 , wherein R1 is piperidinyl claim 1 , R2 and R7 are hydrogen and R3 is OSOH.4. The process of claim 1 , wherein R4 is benzyloxy.5. The process of claim 1 , wherein R5 is benzyloxy and R6 and R7 are hydrogen.6. The process of claim 1 , wherein R5 is allyl or trialkylsilyl and R6 is hydrogen.7. The process of claim 1 , comprising treating the compound of Formula (III) with 9-fluorenylmethoxycarbonyl.8. The process of claim 1 , comprising treating the compound of Formula (III) with N claim 1 ,N-carbonyl diimidazole.9. The process of claim 1 , further comprising treating the compound formed after treatment of compound of Formula (III) with a SOcomplex.10. The process of claim 1 , wherein the compound of Formula (I) is trans-7-oxo-6-(sulphooxy)-1 claim 1 ,6-diazabicyclo[3 claim 1 ,2 claim 1 ,1]octane-2-carboxamide or a pharmaceutically acceptable salt thereof.11. The process of claim 1 , wherein the compound of Formula (I) is sodium ({[(2S claim 1 ,5R)-2-carbamoyl-7-oxo-1 claim 1 ,6-diazabicyclo[3.2.1]oct-6-yl]oxy}sulphonyl)oxidanide.12. The process of claim 1 , wherein the compound of Formula (II) is benzyl (2S claim 1 ,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate.13. The process of claim 1 , wherein the compound of Formula (III) is (2S claim 1 ,5R)-5-[(benzyloxy)amino]piperidine-2-carboxamide.14. The process of claim 13 , comprising treating (2S claim 13 ,5R)-5-[(benzyloxy)amino]piperidine-2-carboxamide to prepare (2S claim 13 ,5R)-6-(benzyloxy)-7-oxo-1 claim 13 ,6-diazabicyclo[3.2.1]octane-2-carboxamide.16. The compound of claim 15 , wherein R5 is benzyloxy and R6 and R7 are hydrogen.17. The compound of claim 15 , wherein R5 is allyl or trialkylsilyl and R6 and R7 are hydrogen.18. The compound of claim 15 , wherein R5 is benzyloxy and R1 claim ...

GLYCOSIDASE INHIBITORS AND USES THEREOF

The invention provides compounds for inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc. 2. (canceled)3. The compound of wherein the compound is selected from the following group:(2S,3R,4S,5R,6R)—N-ethyl-3,4,5-trihydroxy-6-(hydroxymethyl)piperidine-2-carboxamide;(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-N,1-dimethylpiperidine-2-carboxamide;(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-N-methyl-1-(5-methylhexyl)piperidine-2-carboxamide;(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-N-methyl-1-(3-phenylpropyl)piperidine-2-carboxamide;(2S,3R,4S,5R,6R)—N-ethyl-3,4,5-trihydroxy-6-(hydroxymethyl)-1-(3-phenylpropyl)piperidine-2-carboxamide;(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-N-methyl-1-(4-phenylbutyl)piperidine-2-carboxamide;(2S,3R,4S,5R,6R)-1-((E)-3-([1,1′-biphenyl]-4-yl)allyl)-3,4,5-trihydroxy-6-(hydroxymethyl)-N-methylpiperidine-2-carboxamide;(2S,3R,4S,5R,6R)-1-(3-([1,1′-biphenyl]-4-yl)propyl)-3,4,5-trihydroxy-6-(hydroxymethyl)-N-methylpiperidine-2-carboxamide (2S,3R,4S)-1-hexyl-3,4-dihydroxy-N-methylpiperidine-2-carboxamide;(2S,3R,4S,5R)-3,4,5-trihydroxy-N-methylpiperidine-2-carboxamide;(2S,3R,4S,5R)-3,4,5-trihydroxy-N,1-dimethylpiperidine-2-carboxamide;(2S,3R,4S,5R)-3,4,5-trihydroxy-1-methylpiperidine-2-carboxamide;(2S,3R,4S,5R)—N-ethyl-3,4,5-trihydroxypiperidine-2-carboxamide;(2S,3R,4S,5R)—N-ethyl-3,4,5-trihydroxy-1-methylpiperidine-2-carboxamide;(2S,3R,4S,5R,6R)—N-ethyl-3,4,5-trihydroxy-6-methylpiperidine-2-carboxamide;(2S,3R,4S,5R,6R)—N-ethyl-3,4,5-trihydroxy-6-methyl-1-phenethylpiperidine-2-carboxamide;(2S,3R,4S,5R)—N-ethyl-3,4,5-trihydroxy-1-(3-phenylpropyl)piperidine-2-carboxamide;(2S,3S,4R,5S,6R)—N-ethyl-4-fluoro-3,5-dihydroxy-6-methyl-1-phenethylpiperidine-2-carboxamide;(2R, ...