ПРОИЗВОДНЫЕ 2-ИМИНОПИРРОЛИДИНА

Предложены производные 2-иминопирролидина общей формулы (I), их соли и фармацевтические композиции, обладающие антагонистическим действием на рецепторы тромбина. Заместители A, R101, R102, R103, R5, R6, Y1, Y2, кольцо В, Ar определены в формуле изобретения. Технический результат: новые производные 2-иминопирролидина проявляют превосходные эффекты в отношении терапии или предупреждения заболеваний, связанных с тромбином. 9 н. и 28 з.п. ф-лы, 3 ил., 4 табл.

НОВОЕ ПРОИЗВОДНОЕ 3-(4-(БЕНЗИЛОКСИ)ФЕНИЛ)ГЕКС-4-ИНОВОЙ КИСЛОТЫ, СПОСОБ ЕГО ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ДЛЯ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ МЕТАБОЛИЧЕСКОГО ЗАБОЛЕВАНИЯ, ВКЛЮЧАЮЩАЯ ЕГО В КАЧЕСТВЕ ЭФФЕКТИВНОГО ИНГРЕДИЕНТА

Изобретение относится к соединению, представленному формулой 1, его оптическому изомеру или его фармацевтически приемлемой соли:[Формула 1], а также к способам его получения и фармацевтической композиции на его основе. Технический результат: получены новые соединения, обладающие способностью активировать фермент GPR40, пригодные для применения для профилактики или лечения метаболического заболевания. 7 н. и 3 з.п. ф-лы, 7 табл., 77 пр., 2 ил.

АМИДНЫЕ ПРОИЗВОДНЫЕ И ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ, СПОСОБ ИХ ПОЛУЧЕНИЯ И МЕДИЦИНСКОЕ ПРИМЕНЕНИЕ

Настоящее изобретение относится к cоединению общей формулы (I), или его энантиомеру, или их смеси, или его фармацевтически приемлемым солям:В формуле (I) кольцо Р выбрано из пятичленного гетероарила, имеющего от одного до двух гетероатомов, выбранных из группы, состоящей из N, О и S, в качестве атома кольца, и пятичленного гетероциклила, имеющего один гетероатом N в качестве атома кольца; кольцо Q выбрано из фенила и пиридила; А, В или Y выбран из -СН- и N; Rвыбран из алкила, содержащего от 1 до 6 атомов углерода, и циклоалкила, содержащего от 3 до 6 атомов углерода, где указанный алкил, содержащий от 1 до 6 атомов углерода, или циклоалкил, содержащий от 3 до 6 атомов углерода, необязательно дополнительно замещен одной или более чем одной группой, выбранной из группы, состоящей из алкила, содержащего от 1 до 6 атомов углерода, галогена и галогеналкила, содержащего от 1 до 6 атомов углерода; Rвыбран из галогена и галогеналкила, содержащего от 1 до 6 атомов углерода; Rявляются одинаковыми ...

ПРОИЗВОДНЫЕ НАФТАЛИНА, ПРИГОДНЫЕ В КАЧЕСТВЕ ЛИГАНДОВ РЕЦЕПТОРОВ 3 ГИСТАМИНА

Изобретение относится к новым производным нафталина формулы I , а также к их фармацевтически приемлемым солям, которые могут найти применение для лечения и/или профилактики заболеваний, связанных с модулированием Н-3 рецепторов. В формуле I R1 выбран из водорода, низшего алкила, фенила, фенила-низшего алкила и низшего алкоксиалкила; R2 выбран из водорода, низшего алкила, С3-С7-циклоалкила, низшего алкоксиалкила или низшего алкилсульфанилалкила (все значения R1 и R2 приведены в формуле изобретения); или R1 и R2 вместе с атомом азота, к которому они присоединены, образуют 4-7-членное насыщенное или частично ненасыщенное гетероциклическое кольцо, которое может содержать еще один гетероатом, выбранный из атомов азота, кислорода и серы, где указанное гетероциклическое кольцо может быть незамещенным или замещенным 1-2 группами, либо оно может быть конденсировано с незамещенным фенильным кольцом; ! А выбран из ! или ! (значения R3-R7, R9, R10, X, m, n, t, p, q и s приведены в формуле изобретения ...

МОЛЕКУЛЫ С ПЕСТИЦИДНОЙ ФУНКЦИЕЙ И ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ, КОМПОЗИЦИИ И СПОСОБЫ, СВЯЗАННЫЕ С НИМИ

Изобретение относится к молекулам, имеющих пестицидную функцию в отношении вредителей типов членистоногие, моллюски и нематоды. Предложено соединение формулы (1), где R1и R5выбраны из H, F, Cl, Br и I; R2и R4выбраны из H, F, Cl, Br, I, CN, (C1-C4)алкила, (C1-C4)алкокси и (C1-C4)галогеналкила; R3выбран из H, F, Cl, Br, I, NO2и (C1-C4)галогеналкокси; R6и R15выбраны из H и (C1-C4)алкила; R7и R8выбраны из группы, состоящей из F, Cl, Br и I; R9, R10,R11, R12и R14представляют собой H; R13выбран из H, F, Cl, Br, I и (C1-C4)галогеналкила; R16выбран из группы, состоящей из (C3-C8)циклоалкила, азетидинила, изоксазолидинонила, морфолинила, оксазолидинонила, оксетанила, тетрагидрофуранила, тетрагидропиранила, тетрагидротиофенила, тетрагидротиофенил-оксида, тетрагидротиофенил-диоксида, который может быть необязательно замещен одним или более заместителями, выбранными из группы, состоящей из H, F, Cl, Br, I, CN, оксо, (C1-C4)алкила, (C1-C4)галогеналкила, C(=O)O(C1-C4)алкила, (C=O)NH(C1-C4)алкила, (C= ...

ПРОИЗВОДНЫЕ N-(3-АМИНОПРОПИЛ)-N-ФЕНИЛ-5,6,7,8-ТЕТРАГИДРОНАФТАЛИН-2-КАРБОКСАМИДА, СПОСОБ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Производные N-(3-аминопропил)-N-фенил-5,6,7,8-тетрагидронафталин-2-карбоксмида формулы I, где R1 - атом водорода, галоген, метил или алокси, R'1 - водород, галоген, R''1 - Н или метокси, R3 - С1-3-алкил, R4 - 2,3-дигидро-1Н-инден-2-ил, 2,3-дигидро-1Н-инден-1-ил, 1,2,3,4-тетрагидронафталин-1ил-, либо R3 и R4 вместе с несущим атомом азота образуют 1,2,3,4-тетрагидроизохинолил, 6,7-диметокси-1,2,3,4-тетрагидроизохинолил (другие обозначения см. в п.1 ф-лы изобретения), в форме основания или соли, в форме чистого изомера либо смеси таких изомеров, проявляют антиишемическую активность. 6 с. и 1 з.п. ф-лы, 1 табл.

ЦИКЛИЧЕСКИЕ АМИДНЫЕ ПРОИЗВОДНЫЕ КАК ИНГИБИТОРЫ 11-БЕТА-ГИДРОКСИСТЕРОИД-ДЕГИДРОГЕНАЗЫ И ИХ ПРИМЕНЕНИЕ

... 1. Соединение Формулы (I):гдекаждый Rи Rнезависимо выбран из группы, состоящей из Н, метила, CONHC(CH), ОН, COH, СОСН, COCHCH, фенила, СНОН, CN и ОСН;или любые два Rу соседних атомов углерода могут быть объединены с образованием циклического фрагмента, или любые два Rу одного атома углерода, взятые вместе, могут образовывать группу формулы =O;Ar представляет собой необязательно замещенную С-Сгетероарильную группу, выбранную из группы, состоящей из:игде каждый Rнезависимо выбран из группы, состоящей из Н, галогена, ОН, NO, CN, SH, NH, CF, OCF, необязательно замещенного С-Салкила, необязательно замещенного С-Сгалоалкила, необязательно замещенного С-Салкенила, необязательно замещенного С-Салкинила, необязательно замещенного С-Сгетероалкила, необязательно замещенного С-Сциклоалкила, необязательно замещенного С-Сгциклоалкенила, необязательно замещенного С-Сгетероциклоалкила, необязательно замещенного С-Сгетероциклоалкенила, необязательно замещенного С-Сарила, необязательно замещенного C-Сгетероарила ...

СПОСОБ ПРИГОТОВЛЕНИЯ НЕСТЕРОИДНЫХ ПРОТИВОВОСПАЛИТЕЛЬНЫХ СРЕДСТВ И ИХ ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ

... 1. Способ получения соединения в соответствии с общей формулой VIII в энантиомерно чистой форме (эи)>>80% ! ! в которой по меньшей мере одна из групп Х1, Х2, Х3 выбрана из фтора, хлора, брома, гидрокси, метокси, этокси, трифторметила, амино, тогда как другие группы Х1, Х2, Х3 представляют собой атом водорода, ! и в которой по меньшей мере одна из групп Z1, Z2, Z3 выбрана из -O-, -S-, -NH-, -N(-СН3)-, ! тогда как другие группы Z1, Z2, Z3 представляют собой -CH2- группу, и в которой Аr представляет собой ароматическую группу, ! путем взаимодействия соединения в соответствии с общей формулой IV ! ! в которой X1, X2, Х3, Z1, Z2, Z3 имеют значения, указанные выше, ! с энантиомерно чистым 2-гидрокси-4-метил-2-(трифторметил)пентеноатом, с получением соединения общей формулы II ! ! в которой X1, X2, X3, Z1, Z2, Z3 имеют значения, указанные выше, ! и после этого восстанавливают, получая соединение общей формулы I ! ! в которой X1, X2, X3, Z1, Z2, Z3 имеют значения, указанные выше, ! которое затем ...

ПРОИЗВОДНЫЕ 2-ИМИНОПИРРОДИНА

... 1. Соединение, представленное формулой {где кольцо В представляет необязательно замещенное (1) ароматическое углеводородное кольцо или (2) ароматический гетероцикл, необязательно имеющий 1 или 2 атома азота; R101, R102 и R103 являются одинаковыми или различными и каждый представляет (1) водород или (2) группу, выбранную из группы заместителей С, представленной ниже; R5 представляет (1) водород, (2) циано, (3) галоген или (4) группу, выбранную из группы заместителей А, приведенной ниже; R6 представляет (1) водород, (2) С1-6алкил, (3) ацил, (4) карбамоил, (5) гидроксил, (6) С1-6алкокси, (7) С1-6 алкилоксикарбонилокси, (8) С3-8циклоалкил, (9) С1-6алкилоксикарбонил, необязательно замещенный ацилоксигруппой, или (10) С6-14ароматическую углеводородную кольцевую группу или 5-14-членную ароматическую гетероциклическую группу (причем каждый из предыдущих членов является необязательно замещенным по меньшей мере одной группой, выбранной из группы заместителей Е); Y1 представляет простую связь, -(CH2 ...

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 ...

ПОЛИМОРФНЫЕ ФОРМЫ СОЕДИНЕНИЯ ST-246 И СПОСОБЫ ПОЛУЧЕНИЯ

... 1. Полиморф формы I 4-трифторметил-N-(3,3а,4,4а,5,5а,6,6а-октагидро-1,3-диоксо-4,6-этеноциклопроп[f]изоиндол-2(1Н)-ил)бензамида (соединение ST-246), который демонстрирует картину рентгеновской порошковой дифракции, имеющую характеристические пики при угле отражения 2θ приблизительно 7,63, 10,04, 11,47, 14,73, 15,21, 15,47, 16,06, 16,67, 16,98, 18,93, 19,96, 20,52, 20,79, 22,80, 25,16, 26,53, 27,20, 27,60, 29,60, 30,23, 30,49, 30,68, 31,14, 33,65, 34,33, 35,29, 35,56, 36,30, 37,36, 38,42, 38,66 градусов.2. Полиморф по п.1, который представляет собой изолированный полиморф, и который является по меньшей мере приблизительно на 70% свободным от других форм, предпочтительно является по меньшей мере приблизительно на 80% свободным от других форм, более предпочтительно является по меньшей мере приблизительно на 90% свободным от других форм, еще более предпочтительно является по меньшей мере приблизительно на 95% свободным от других форм, в частности является по меньшей мере приблизительно на 99% ...

ПРОИЗВОДНЫЕ ГИДРОБЕНЗАМИДА В КАЧЕСТВЕ ИНГИБИТОРОВ Hsp90

... 1. Кислотно-аддитивная соль соединения формулы (1). ! , ! которая представляет собой соль, образованную молочной кислотой, например L-молочной кислотой. ! 2. Кислотно-аддитивная соль, по существу, в кристаллической форме по п.1, где кристаллическую форму выбирают из форм FB3, FB4, FB6, FH3, FL1, FL2, FS3, FS4 и FS7. ! 3. Кислотно-аддитивная соль, по существу, в кристаллической форме по п.2, где кристаллическую форму выбирают из форм FL1 и FL2, как определено в настоящем описании. ! 4. Способ получения соединения формулы (2): ! ! где R1 представляет собой C1-4 алкил; указанный способ включает: ! или каталитическое гидрирование соединения формулы (3): ! ! где PG представляет собой защитную группу, удаляемую в условиях гидрирования, и A-B представляет собой CH-CH3 или C=CH2, и после этого, когда соединение формулы (2) получают в виде свободного основания, необязательное преобразование свободного основания в кислотно-аддитивную соль; или ! (a-i) взаимодействие соединения формулы (4), или его ...

ПРОИЗВОДНЫЕ ПЕРГИДРОИЗОИНДОЛА И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

Изобретение относится к новым производным пергидроизоиндола общей формулы 1, в которой символы R идентичные и представляют радикалы фенила, замещенные в случае необходимости атомом галогена или радикалом метила в положении 2 или 3, символ R' представляет радикал фенила, замещенный в положении 2 радикалом алкила или алкилокси, содержащим 1 или 2 атома углерода, символ R'' - атом фтора или радикал гидрокси, символ R ''' - атом водорода, или символы R'' и R''' - радикалы гидрокси, или символ R'' образует с R''' связь, и символ R° представляет атом водорода или защитный радикал, а также их соли и их получение. Продукты по изобретению являются промежуточными соединениями синтеза для получения производных, обладающих антагонистической активностью относительно вещества R.

Производные изоиндолина для применения в лечении вирусной инфекции

АЦИЛАМИНОЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ КОНДЕНСИРОВАННЫХ ЦИКЛОПЕНТАНКАРБОНОВЫХ КИСЛОТ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ФАРМАЦЕВТИЧЕСКИХ СРЕДСТВ

... 1. Соединение формулы I в любой из его стереоизомерных форм или сочетании стереоизомерных форм в любом соотношении, или его физиологически приемлемая соль, или физиологически приемлемый сольват любого из них ! ! где кольцо A является циклоалкановым кольцом с числом членов от 3 до 7, бензольным кольцом или моноциклическим 5-членным или 6-членным ароматическим гетероциклическим кольцом, содержащим 1 или 2 одинаковых или разных гетерочленов кольца, выбранных из группы, содержащей N, N(R0), O и S, причем циклоалкановое кольцо может необязательно иметь один или более одинаковых или разных заместителей, выбранных из группы, содержащей фтор и (C1-C4)-алкил, а бензольное и гетероциклическое кольца могут необязательно иметь один или более одинаковых или разных заместителей, выбранных из группы, содержащей галоген, R1, HO-, R1-O-, R1-C(O)-O-, R1-S(O)2-O-, R1-S(O)m-, H2N-, R1-NH-, R1-N(R1)-, R1-C(O)-NH-, R1-C(O)-N(R71)-, R1-S(O)2-NH-, R1-S(O)2-N(R71)-, R1-C(O)-, HO-C(O)-, R1-O-C(O)-, H2N-C(O)-, R1 ...

ИНГИБИТОРЫ NAMPT И ROCK

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

Способ получения -(аминофенил)алифатических карбоновых кислот или их солей

PERHYDROISOINDOL-DERIVATE, DEREN HERSTELLUNG UND DIE SIE BEHALTENDE PHARMAZEUTISCHE ZUSAMMENFASSUNGEN

VERFAHREN ZUR HERSTELLUNG VON NEUEN NAPHTHYLDERIVATEN

Cyclische Nitrone und pharmazeutische Mittel die sie enthalten

Cyclische Pyrrolketone und Verfahren zu ihrer Herstellung

SULFONAMID-DERIVATE ALS 5-HT6 RECEPTOR ANTAGONISTEN UND VERFAHREN ZU IHRER HERSTELLUNG

"NEUE BENZOESAEUREN, IHRE HERSTELLUNG UND IHRE VERWENDUNG ALS ARZNEIMITTEL"

AMINOSÄUREDERIVATE, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL UND VERFAHREN ZU IHRER HERSTELLUNG

PYRROL SUBSTITUIERTE INDOLIN-2-ON PROTEIN KINASE INHIBITOREN

CYCLISCHE NITRONE UND PHARMAZEUTISCHE ZUSAMMENSETZUNGEN DIE SIE ENTHALTEN

Compounds

HYDRATROPIC ACID DERIVATIVES AND PREPARATION THEREOF

... 1435050 Hydratropic acid derivatives MERCK PATENT GmbH 25 Nov 1974 [26 Nov 1973] 50946/74 Heading C2C Novel compounds I in which R1 is H, C 1-4 alkyl, 2-acetamidoethyl, 1 - methyl - 4 - piperidyl or 2,3 - dihydroxypropyl, R2 is Hal, phenyl, 4-Hal-phenyl, 4-Halphenoxy, 4 - Hal - phenoxymethyl, 1,2,3,4- tetrahydro - 1 - naphthyl, 1 - pyrryl, piperidino, isoindolino, 1,2,3,4-tetrahydroquinolino, 1,2,3,4 - tetrahydro - 4 - quinolyl or 1 - methyll,2,3,4-tetrahydro-4-quinolyl and Hal is F, Cl or Br, and their physiologically acceptable salts with acids or bases, are prepared by (a) condensing a phenol II or a salt thereof, with a compound III in which X is Cl, Br, I, OH or esterified OH, or (b) methylating a compound IV or a metal derivative thereof, or (c) treating a compound V in which Z is a functionally modified carboxyl group but is different from COOR1, with a solvolysing agent. The resulting compound I may be treated to convert the R1 radical thereof ...

METAL CHELATE IMINOTHIAZOLE-IMINOISOINDOLINE PIGMENTS

... 1424449 Polymer compositions containing metal chelateiminothiazole-iminoisoindoline pigments STERLING DRUG Inc 9 Nov 1973 [20 Nov 1972] 52165/73 Headings C3P and C3R [Also in Division C4] Metal chelate pigments have the formula wherein A is a divalent radical combining with the -C=C- portion of the molecule to which it is attached to form a six-membered carbocyclic ring and has the formula or wherein each instance C(7) and C(4) are bonded to C(7a) and C(3a) respectively; Me is Cu, Co or Ni; Y is a divalent radical combining with the -S-C-C- portion of the molecule to form a five-membered heterocyclic ring having the same orientation as a thiazole ring and is -C(=Z)-NH- or -C-(N=B)=N- in which Z is NH, O or S, and -N=B is loweralkylamino, di-lower-alkylamino, piperidino, pyrrolidino, morpholino, phenylamino, (loweralkyl) - (phenyl)amino, phenyl - lower - alkylamino or (lower-alkyl)-(phenyl-lower-alkyl)amino; and An is an anion. R, R 1 , R 2 and R 3 are the same or different hydrogen, alkyl ...

Preparation of highly pure salts of citalopram

Preparing high purity citalopram salts comprises:

New derivatives of 5-amino-isoindoline

The invention comprises 5-amino isoindolines of the general formula wherein R1 is a hydrogen atom and R11 is a COR111 group, R111 being a hydrogen atom or an aliphatic, araliphatic, aromatic, or heterocyclic radical; or R1 is a COR111 group and R11 is a hydrogen atom a COR111 group or an aliphatic radical; salts thereof with physiologically acceptable acids and the preparation of such compounds when R is a hydrogen atom and R11 is a COR11 group, by acylating 5 -nitro-isoindoline and reducing the aromatic nitro group; when R1 is a COR111 group and R11 is a hydrogen atom, by providing the heterocyclic nitrogen atom with a protective grouping, acylating the 5-amino group and then removing the protective group; when R1 is COR111 and R11 is an aliphatic radical, by acylating a 5-amino isoindoline bearing an aliphatic radical in the 2-position; and when both R1 and R11 are both COR111 radicals, by acylating 5-amino-isoindoline.ALSO:Pharmaceutical compositions having analgesic ...

Compounds

Tetrapeptide analogs

New isoindole derivatives and process for their manufacture

The invention comprises isoindole dyestuffs of the general formula wherein aryl and arylene are equal or different aromatic mono- or multi-nuclear residues which may contain further substituents, and the aryl residue is free of hydroxyl groups in the ortho position. The dyestuffs may be made by condensing derivatives of the dihydroisoindolone of the formula wherein X signifies hydrogen, or hydroxyl, alkoxy, aryloxy, carbonamido, ureido, carbalkoxyamido, primary, secondary or tertiary amino radicals, or a halogen atom, with a phosphoryl halide and/or a phosphorus pentahalide. The dyestuffs may be used for dyeing and printing cotton, regenerated cellulose, polyacrylonitrile, polyamides and polyesters, for pigmenting plastics or spin-dyeing polyesters.

Tetrahydro-2H-Benzo(C)Pyrroles

A tetrahydro-2H- benzo?c!pyrrole compound of the general formula wherein R<1> is H or R<2>; Am is N(R<2>)2; and each R<2> is independently allyl, methyl, ethyl, or n-propyl; and the pharmaceutically-acceptable acid addition salts thereof.

COMPOSITION,PROCESS AND USE

ISOINDOLE DERIVATIVES

... 1526267 Esters and amides of 2-aminoalkyl- 3-phenylisoindole-1-carboxylic acids F HOFFMANN-LA ROCHE & CO AG 27 Nov 1975 [28 Nov 1974 23 Sept 1975] 48804/75 Heading C2C The invention comprises compounds of formula and their pharmaceutically acceptable acid addition salts, wherein A is C 2-10 alkylene; Z is -OR or R is alkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, allyl or aralkyl; R 1 , R 2 , R 3 and R 4 are each H, halogen, CF 3 , alkyl or alkoxy; R 5 and R 6 are each H, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, aryl or aralkyl or R 5 and R 6 are together -(CH 2 ) n -, in which n is 2-7, or R 5 and R 6 are, together with the nitrogen atom to which they are attached, a 5- or 6-membered heterocyclic ring containing an oxygen atom or a further nitrogen atom which may be substituted by alkyl or hydroxyalkyl; and R 7 and R 8 are each H, alkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl or aralkyl with the proviso that at least one of R 7 and R 8 is other than H. In examples ...

ISOINDOLE DERIVATIVES

... 1526270 Isoindoles F HOFFMANN-LA ROCHE & CO AG 27 Nov 1975 [28 Nov 1974 23 Sept 1975] 06708/77 Divided out of 1526267 Heading C2C The invention comprises compounds of formula wherein Y represents the group A represents an alkylene group containing 2-10 carbon atoms, A1 and A11 each represent an alkylene group containing 1-9 carbon atoms, R1 represents an alkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl or aralkyl group, R 1 , R 2 , R 3 and R 4 each independently represent a hydrogen or halogen atom or an alkyl, alkoxy or trifluoromethyl group, R1 5 and R1 6 each independently represent an alkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, aryl or aralkyl group or R1 5 and R1 c together represent the group -(CH 2 ) n -, wherein n stands for an integer from 2-7, or R1 5 and R1 6 together with the nitrogen atom to which they are attached represent a 5-membered or 6-membered heterocyclic ring containing an oxygen ...

Matrix metallproteinase inhibitors

Method of preparation of iminodiacides substituted.

Benzènesulfonyl-semicarbazides and their preparation.

Method of inhibiting amyloid protein aggregation and imaging amyloid deposits using isoindoline derivatives

Method of inhibiting amyloid protein aggregation and imaging amyloid deposits using isoindoline derivatives.

The present invention provides a method of treating Alzheimer's disease using a medicament derived from a novel compound of formula I, Also provided is a treatment for inhibiting the aggregation of amyloid proteins using a medicament derived from a compound of Formula I and a procedure for imaging amyloid deposits using isoindoline derived medicaments.

Sulfamoyl-phenyl-ureido benzamidine-derivatives asantimalarial agents.

NOVEL HETEROCYCLIC COMPOUNDS

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Matrix metalloproteinase inhibitors

Sulfamoyl-phenyl-ureido benzamidine-derivatives asantimalarial agents

Polymorphic forms ST-246 and methods of preparation

Process for making N-ARYL-ANTHRANILIC acids and their derivatives.

The present invention relates to a process for the preparation of N-arylanthranilic acids, and a process for the preparation of N-aryl anthranilic esters, amides, and hydroxamic esters.

Method of inhibiting amyloid aggregation and imaging amyloid deposits.

The present invention provides a method of treating alzbeimer's disease using a compound of formula (i)and a method of imaging amyloid deposits, as well as new compounds of formula (i).

Method of inhibiting amyloid protein aggregation and imaging amyloid deposits using isoindoline derivatives

Novel dideptidyl peptidase IV inhibitors, pharmaceutical compositions containing them, and proces for their preparation

'(2-Hydroxy-2-(4-hydroxy-3-hydoxymethylphenyl)-ethylamino)-propyl!phenyl derivatives as BETA2 agonists.

Matrix metallproteinase inhibitors

PHOSPHONATE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Polymorphic forms ST-246 and methods of preparation

Method of inhibiting amyloid protein aggregation and imaging amyloid deposits.

TERTIARY AMINOACIDS, PROCESS FOR THEIR MANUFACTURE AND COMPOSITIONS CONTAINING THEM

Anti-hypertentifs agents, pharmaceutical compositions the container and method of preparation of the aforesaid agents and compositions.

Derived from 2-amino-5- (o-sulfamidophényl) - 1,3,4, - thiadiazol usable like antivirus, and proceeded agents for their preparation.

Method of preparation of cyclic tertiary amoebas.

Method of inhibiting amyloid protein aggregation and imaging amyloid deposits using isoindoline derivatives.

Tertiary amino-acids.

Process for the preparation of tertiary amino-acids.

(2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)-ethylamino)-propyl-phenyl derivatives as beta2 agonists.

Method of inhibiting amyloid protein aggregation and imaging amyloid deposits

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Method of inhibiting amyloid protein aggregation and imaging amyloid deposits using isoindoline derivatives

COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Polymorphic forms ST-246 and methods of preparation

Novel dideptidyl peptidase IV inhibitors, pharmaceutical compositions containing them, and proces for their preparation

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

'(2-Hydroxy-2-(4-hydroxy-3-hydoxymethylphenyl)-ethylamino)-propyl!phenyl derivatives as BETA2 agonists.

Sulfamoyl-phenyl-ureido benzamidine-derivatives asantimalarial agents.

NOVEL HETEROCYCLIC COMPOUNDS

Matrix metallproteinase inhibitors

COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

'(2-Hydroxy-2-(4-hydroxy-3-hydoxymethylphenyl)-ethylamino)-propyl!phenyl derivatives as BETA2 agonists.

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

PHOSPHONATE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Process for making n-aryl-antranilic acids and their derivatives

Process for making n-aryl-antranilic acids and their derivatives

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

PHOSPHONATE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Novel dideptidyl peptidase IV inhibitors, pharmaceutical compositions containing them, and proces for their preparation

NOVEL HETEROCYCLIC COMPOUNDS

Sulfamoyl-phenyl-ureido benzamidine-derivatives asantimalarial agents.

OXOPHENYLCYCLOHEXYLPROPANOLAMINDERIVATE, THEIR PRODUCTION AND USE IN THERAPEUTIKA

PROCEDURES FOR the PRODUCTION OF NEW ONE, HETERO-CYCLIC SUBSTITUTED 5-SULFAMOYLBENZOESAEUREDERIVATEN AND YOUR SALTS

PROCEDURE FOR THE PRODUCTION OF NEW OF CONJUGATED AMINO KETONES AND YOUR NICHTTOXI SALTS

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

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

Acetylene derivatives having mglur 5 antagonistic activity

The invention provides compounds of formula I wherein n, A, R, R′, R″, R O , X and Y are as defined in the description, and their preparation. The compounds of formula I are useful as pharmaceuticals.

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.

New compounds, pharmaceutical compositions and uses thereof

The invention relates to new compounds of the formula I to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

Motion-based device operations

Methods, program products, and systems of motion-based device operations are described. A mobile device can coordinate operations of a motion sensor and a proximity sensor. The mobile device can determine a gesture event using the motion sensor. The mobile device can determine a proximity event using the proximity sensor. The mobile device can use the gesture event and proximity event to confirm one another, and determine that the mobile device has moved in proximity to a target object following a specified gesture. Upon confirmation, the mobile device can perform a specified task.

Compositions and Methods for Enhancing Proteasome Activity

Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp 14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

2-PHENYL BENZOYLAMIDES

Compounds of Formula I that inhibit microsomal triglyceride transfer protein (MTP) and/or apolipoprotein B (Apo B) secretion and their uses in the treatment of diseases linked thereto in animals are described herein. 2. A compound according to wherein Ris —C(O)—N—RRand q is 0.5. A compound according to wherein p is 0 and Ris hydrogen or (C-C)alkyl.6. A compound according to wherein Ris —C(O)—O—(C-C)alkyl.7. A compound according to wherein m and n are each independently 0 or 1 and Rand Rare each independently (C-C)alkyl claim 6 , (C-C)alkoxy or trifluoromethyl.8. The compound:Ethyl (1R)-1-({2-[3-(Dimethylcarbamoyl)-4-({[6-methyl-4′-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)phenyl]acetoxy}methyl)-2-methyl-3-oxoisoindoline-1-carboxylate;Ethyl (1R)-1-({2-[3-(dimethylcarbamoyl)-4-{[(4′-isopropoxybiphenyl-2-yl)carbonyl]amino}phenyl]acetoxy}methyl)-2-methyl-3-oxoisoindoline-1-carboxylate;Ethyl 1-({2-[3-(dimethylcarbamoyl)-4-({[5-methyl-4′-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)phenyl]acetoxy}methyl)-2-methyl-3-oxoisoindoline-1-carboxylate;Ethyl 7-({2-[3-(dimethylcarbamoyl)-4-({[5-methyl-4′-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)phenyl]acetoxy}methyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-7-carboxylate;Ethyl 7-({2-[3-(dimethylcarbamoyl)-4-({[6-methyl-4′-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)phenyl]acetoxy}methyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-7-carboxylate:Ethyl (1R)-1-({2-[3-(dimethylcarbamoyl)-4-({[5-methoxy-4′-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)phenyl]acetoxy}methyl)-2-methyl-3-oxoisoindoline-1-carboxylate;Ethyl (1R)-1-({2-[3-(dimethylcarbamoyl)-4-({[6-methoxy-4′-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)phenyl]acetoxy}methyl)-2-methyl-3-oxoisoindoline-1-carboxylate;Ethyl (1R)-1-({2-[3-(dimethylcarbamoyl)-4-{[(4′-isopropoxy-5-methylbiphenyl-2-yl)carbonyl]amino}phenyl]acetoxy}methyl)-2-methyl-3-oxoisoindoline-1-carboxylate;Ethyl 7-({2-[3-(dimethylcarbamoyl)-4-{[(4′-isopropoxybiphenyl-2-yl)carbonyl]amino}phenyl]acetoxy}methyl ...

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.

4-carboxybenzylamino derivatives as histone deacetylase inhibitors

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

Novel hydroxamates as therapeutic agents

The present invention is directed to certain hydroxamate derivatives that are useful in the treatment of hepatitis C. These compounds are also inhibitors of histone deacetylase and are therefore useful in the treatment of diseases associated with histone deacetylase activity. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.

BENZAMIDE DERIVATIVES AND THEIR USE AS HSP90 INHIBTORS

The invention provides a compound which is (a) a phenylamide derivative of formula (I) or a tautomer thereof, or (b) a pharmaceutically acceptable salt, N-oxide, hydrate, prodrug or solvate thereof: wherein R, R, R, R, R, Rand Rare as defined herein. The compounds are useful in the treatment of diseases mediated by HSP90. 2. A compound as claimed in wherein Ris hydroxy.3. A compound as claimed in wherein R claim 1 , R claim 1 , Rand Rare the same or different and represent hydrogen or halogen atoms or hydroxy claim 1 , unsubstituted Calkyl or unsubstituted Calkoxy groups.4. A compound as claimed in wherein either:{'sup': 6', '7', '8', '9', '8', '9, 'sub': 3', '1-4', '1-4, '(i) Rrepresents —CH, Rrepresents —CRR-A wherein Rand Rare the same or different and represent a hydrogen or halogen atom or an unsubstituted Calkyl or Calkoxy group, and A represents a phenyl ring substituted with a group W; or'}{'sup': 6', '7, 'sub': 1-4', '1-4', '1-4', '1-4', '1-4', '1-2, '(ii) Rand R, together with the nitrogen atom to which they are bonded, form a pyrrolidinyl, piperidinyl or isoindolinyl group which is substituted with a group W and is optionally further substituted with 1 or 2 groups which are the same or different and are selected from halogen atoms and unsubstituted Calkyl, Calkoxy, hydroxyl, Chaloalkyl, Chaloalkoxy, Chydroxyalkyl, cyano, nitro, —SR′ and —NR′R″ groups where R′ and R″ are the same or different and represent hydrogen or unsubstituted Calkyl.'}5. A compound as claimed in wherein Alkrepresents a bond claim 1 , an unsubstituted Calkylene group claim 1 , or an unsubstituted —(Calkylene)-NH—(Calkylene)- group.6. A compound as claimed in wherein either:{'sup': 12', '13, 'sub': 1-6', '3-7', '6-10', '1-4', '6-10', '1-4', '3-7, '(i) Rand Rare the same or different and represent hydrogen, Calkyl, Ccarbocyclyl, Caryl, —(Calkyl)-(Caryl), or —(Calkyl)-(Ccarbocyclyl); or'}{'sup': 12', '13, 'sub': '3-7', '(ii) Rand R, together with the carbon atom to which they are bonded, ...

Pharmaceutical Compounds

The invention provides a compound of the formula (1): or a salt, solvate, N-oxide or tautomer thereof.

PROCESS AND INTERMEDIATES FOR PREPARING MACROLACTAMS

The present invention relates to macrolactam compounds, intermediates useful in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing and modifying macrolactams. One use of the compounds and methods described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. An example of an HCV inhibitory compound that can be synthesized using the procedures described herein is Compound A and derivative thereof. 7. The method of claim 6 , wherein Ris Calkyl and Ris a H or Calkyl.10. The method of claim 9 , wherein said Step C coupling is performed using EDC and pyridine or a pyridine derivative.13. The method of claim 8 , wherein Ris either H or Calkyl.17. The method of claim 13 , wherein Ris either H or Calkyl.19. The method of claim 8 , wherein said ring closure is performed by slow addition of catalyst and the compound of Formula IIa to a solvent at approximately the same time claim 8 , wherein:said solvent is provided at about 5-25 liters per Kg of substrate;said catalyst is provided at a concentration of about 250 ml to 3 L per Kg of catalyst;said compound is provided at a concentration of about 500 ml to 6 L per Kg of substrate; andsaid compound-solution, said catalyst-solution and said solvent are combined together over a period of 0.5-2.5 hrs.2122-. (canceled) The present invention relates to method and compounds that can be used to produce macrolactams, and modify macrolactams. One use of the methods and compounds described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity.Hepatitis C virus (HCV) infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals. Current treatments for HCV infection include immunotherapy with recombinant interferon-α alone or in combination with the nucleoside analog ribavirin. Several virally-encoded ...

ISOINDOLONE DERIVATIVES

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

MATRIX METALLOPROTEINASE INHIBITORS

The present invention relates to β-hydroxy and amino-substituted carboxylic acids, which act as matrix metalloproteinase inhibitors, particularly diastereomerically pure β-hydroxy carboxylic acids, corresponding processes for their synthesis, and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune, and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase. 2. A compound which is selected from:(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[6-(3-fluoro-4-methoxyphenyl)pyridin-3-yl]-3-hydroxypentanoic acid (Compound No. 55);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[6-(4-methoxyphenyl)pyridin-3-yl]pentanoic acid (Compound No. 57);(2S,3R)-5-[6-(4-chlorophenyl)pyridin-3-yl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 59);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 60);(2S,3R)-5-[4-(4-chlorophenyl)-2-thienyl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 61);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)-2-thienyl]pentanoic acid (Compound No. 62);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-{4-[4-(trifluoromethyl)phenyl]-2-thienyl}pentanoic acid (Compound No. 63 ...

TETRAHYDROISOQUINOLINE DERIVATIVE

To provide an excellent agent for preventing or treating dementia and schizophrenia based on serotonin 5-HTreceptor regulating action, it was found that a tetrahydroisoquinoline derivative characterized by a structure in which an acylguanidino group binds to a N atom of a tetrahydroisoquinoline ring or the like, and a cyclic group binds to an unsaturated ring has a potent 5-HTreceptor regulating action and an excellent pharmacological action based on the regulating action and also discovered that the tetrahydroisoquinoline derivative is useful as an agent for treating or preventing dementia, schizophrenia, and the like, whereby the present invention has been completed. 2. The compound according to or a pharmaceutically acceptable salt thereof claim 1 ,{'sup': 1', '1', '2', '3', '4, 'wherein Rrepresents phenyl, pyridyl, or cycloalkyl which may be respectively substituted with group(s) selected from G, Rrepresents halogen, m represent 1, n represents 1, and both Rand Rrepresent H.'}3. The compound according to or a pharmaceutically acceptable salt thereof claim 1 ,{'sup': 1', '2', '3', '4, 'wherein Rrepresents phenyl which may be substituted with halogen or —O-(lower alkyl), Rrepresents H, F, Cl, or methyl, m represents 1, n represents 1, and both Rand Rrepresent H.'}4. The compound according to or a pharmaceutically acceptable salt thereof claim 1 ,{'sup': 1', '2', '3', '4, 'wherein Rrepresents pyridyl which may be substituted with halogen or —O-(lower alkyl), Rrepresents H, F, Cl, or methyl, m represents 1, n represents 1, and both Rand Rrepresent H.'}5. The compound according to or a pharmaceutically acceptable salt thereof claim 1 ,{'sup': 1', '2', '3', '4, 'wherein Rrepresents phenyl which may be substituted with halogen or —O-(lower alkyl), Rrepresents H, F, Cl, or methyl, m represents 1, n represents 1, and Rand Rform cyclopropane-1,1-diyl or cyclobutane-1,1-diyl together with the carbon atom binding thereto, as ethylene or trimethylene.'}6. A compound selected ...

ACETYLENE DERIVATIVES HAVING MGLUR 5 ANTAGONISTIC ACTIVITY

The invention provides compounds of formula I 1. A compound of formula Im is 0 or 1,n is 0 or 1 andA is hydroxyX is hydrogen andY is hydrogen, orA forms a single bond with X or with Y;{'sub': 0', '1-4', '1-4', '1', '1', '1-4', '2', '2', '1-4, 'Ris hydrogen. (C)alkyl, (C)alkoxy, trifluoromethyl, halogen, cyano, nitro, —COORwherein Ris (C)alkyl or —CORwherein Ris hydrogen or (C)alkyl, and'}{'sub': 3', '3', '4', '5', '2', '6', '3', '1-4', '3-7', '4', '5', '1-4', '3', '1-4', '3-7, 'R is —COR, —COOR, —CONRRor —SOR, wherein Ris (C)alkyl, (C)cycloalkyl or optionally substituted phenyl, 2-pyridyl or 2-thienyl, Rand R, independently, are hydrogen or (C)alkyl and Ris (Calkyl, (C)cycloalkyl or optionally substituted phenyl,'}{'sub': '1-4', 'R′ is hydrogen or (C)alkyl and'}{'sub': '1-4', 'R″ is hydrogen or (C)alkyl, or'}{'sub': 2', '2', 'p, 'claim-text': 'wherein p is 0, 1 or 2, in which case one of n and p is different from 0,', 'R′ and R″ together form a group —CH—(CH)—'}whereinwith the proviso that Ris different from hydrogen, trifluoromethyl and methoxy when m is 1, n is 0, A is hydroxy, X and Y are both hydrogen, R is COOEt and R′ and R″ together form a group —(CH)—, The present invention relates to novel acetylene derivatives, their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them.More particularly the invention provides a compound of formula IwhereinOn account of the asymmetrical carbon atoms present in the compounds of formula I and their salts, the compounds may exist in optically active form or in form of mixtures of optical isomers, e.g. in form of racemic mixtures. All optical isomers and their mixtures including the racemic mixtures are part of the present invention.In a further aspect, the invention provides a process for the production of the compounds of formula I and their salts, which comprises the step ofThe reaction of process a) can be effected according to conventional methods, e.g. as described in Examples 1 (step ...

NITROGEN-CONTAINING CONDENSED HETEROCYCLIC COMPOUND

There are provided compounds represented by the following general formula (I) or pharmaceutically acceptable salts of thereof, which have a superior monoacylglycerol acyltransferase 2 inhibitory action: 3. The compound of the general formula (I) above or pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris the formula (II).4. The compound of the general formula (I) above or pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sup': 'B', 'Ris the formula (II),'}{'sup': 11', '12', '11', '12', '11', '12, 'sub': 1-4', '3-6, 'V is the formula —CRR—, wherein Rand R, which may be the same or different, each represent a hydrogen atom or a Calkyl group, or Rand R, taken together with the adjacent carbon atom, may form Ccycloalkane,'}m is 1, andn is 0.5. The compound of the general formula (I) above or pharmaceutically acceptable salt thereof according to claim 3 , wherein{'sup': 11', '12', '11', '12, 'sub': '1-4', 'V is the formula —CRR—, wherein Rand R, which may be the same or different, each represent a hydrogen atom or a Calkyl group,'}m is 1, andn is 0.6. The compound of the general formula (I) above or pharmaceutically acceptable salt thereof according to claim 3 , whereinV is the formula —CO—NH—,W is a single bond,m is 1, andn is 0.7. The compound of the general formula (I) above or pharmaceutically acceptable salt thereof according to claim 3 , whereinV is the formula —CO—NH—,W is a single bond,m is 0, andn is 0.8. The compound of the general formula (I) above or pharmaceutically acceptable salt thereof according to claim 1 , wherein Ring A is an aryl group which may be substituted by 1 to 3 substituents claim 1 , which may be the same or different claim 1 , selected from the group consisting of (i) to (vii) below:(i) a halogen atom,(ii) a hydroxy group,{'sub': '1-8', '(iii) a Calkyl group which may be substituted by 1 to 3 substituents, which may be the same or different, selected from the group consisting ofa hydroxy group ...

Inhibitors of Histone Deacetylase

The present invention relates to compounds of formula (I): 10. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.11. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.12. The method of claim 11 , wherein the condition is selected from a neurological disorder claim 11 , memory loss or impairment claim 11 , cognitive function disorder or impairment claim 11 , extinction learning disorder claim 11 , fungal disease or infection claim 11 , inflammatory disease claim 11 , hematological disease claim 11 , and neoplastic disease.13. The method of claim 11 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, phobia, social anxiety disorder, substance dependence recovery or Age Associated Memory Impairment (AAMI), or Age Related Cognitive Decline (ARCD);a hematological disease selected from acute myeloid leukemia, acute promyelocytic leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, myelodysplastic syndromes, and sickle cell anemia;a cancer; andan extinction learning disorder selected from a fear extinction deficit and post-traumatic ...

INHIBITORS OF MITOCHONDRIAL PYRUVATE DEHYDROGENASE KINASE ISOFORMS 1-4 AND USES THEREOF

The present disclosure relates to the identification of PDK inhibitors and their use in the treatment of diseases such as diabetes, cardiovascular disease and cancer. The invention relates to the development of robust PDK inhibitors that can be used to improve glucose metabolism and correct metabolic dysfunction in vivo. Based on the unique structural features present in the ATP-binding pocket of PDK2, a single functional-group change was made in a known Hsp90 inhibitor that binds to the corresponding pocket of the latter protein from the GHKL family. This approach efficiently converted the Hsp90 inhibitor to a highly specific inhibitor for all PDK isoforms. These final PDK inhibitors of this series robustly augments PDC activity with reduced phosphorylation in tissues. 3. The compound of claim 1 , wherein Xis hydrogen.4. The compound of claim 1 , wherein Xis oxo.5. The compound according to claim 1 , wherein Xand Xare each independently hydrogen.6. The compound according to claim 1 , wherein Xand Xare each independently hydroxy or alkoxy.7. The compound according to claim 1 , wherein Xand Xare each independently methoxy.8. The compound according to claim 1 , wherein Xand Xare each independently hydrogen.9. The compound according to claim 1 , wherein Xand Xare each independently hydroxy or alkoxy.10. The compound according to claim 1 , wherein Xand Xare each independently methoxy.11. The compound according to claim 1 , wherein Xand Xare each independently amino claim 1 , alkylamino claim 1 , heterocycloalkylamino claim 1 , substituted alkylamino claim 1 , or substituted heterocycloalkylamino.13. The compound according to claim 1 , wherein Xis hydrogen.14. The compound according to claim 1 , wherein Xis alkyl claim 1 , alkenyl claim 1 , aryl claim 1 , or a substituted version of any of these groups.15. The compound according to claim 1 , wherein Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , and Yare each independently hydrogen.16. The compound according to claim 1 ...

ISOINDOLINE COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE

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

2-CYANOISOINDOLINE DERIVATIVES FOR TREATING CANCER

The invention relates to novel compounds of formula I which are inhibitors of deubiquitylating enzymes (DUBs) and/or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to methods for the preparation of these compounds and to their use in the treatment of cancer. 2. The compound according to claim 1 , wherein Xis N or C-Q-(R)wherein n is 0 and Qis hydrogen.3. The compound according to claim 1 , wherein Ris unsubstituted or substituted with halogen claim 1 , cyano claim 1 , oxo claim 1 , nitro claim 1 , hydroxyl claim 1 , —CF claim 1 , —SR claim 1 , —C-Calkyl claim 1 , —C-Calkoxy claim 1 , —C-Calkenyl claim 1 , —C-Calkynyl claim 1 , -Q-R claim 1 , -Q-O-Q-R claim 1 , -Q-S-Q-R claim 1 , -Q-SO-Q-R claim 1 , -Q-NRCONRR claim 1 , -Q-NRCONR-Q-R claim 1 , -Q-NRR claim 1 , -Q-NR-Q-R claim 1 , -Q-COR claim 1 , -Q-CO-Q-R claim 1 , -Q-NRCOR claim 1 , -Q-NRCO-Q-R claim 1 , -Q-NRC(O)OR claim 1 , -Q-NRC(O)O-Q-R claim 1 , -Q-SOR claim 1 , -Q-SO-Q-R claim 1 , -Q-CONRR claim 1 , -Q-CONR-Q-R claim 1 , -Q-COR claim 1 , -Q-CO-Q-R claim 1 , -Q-SONRR claim 1 , -Q-SONR-Q-R claim 1 , -Q-NRSOR claim 1 , -Q-NRSO-Q-R claim 1 , -Q-NRSONRR claim 1 , and -Q-NRSONR-Q-R; wherein{'sup': 3a', '3b, 'sub': 1', '6', '2', '6, 'Qand Qindependently represent a covalent bond optionally substituted C-Calkylene or optionally substituted C-Calkenylene;'}{'sup': 10', '11', '11a, 'sub': 1', '6, 'R, Rand Reach independently represent hydrogen or optionally substituted C-Calkyl; and'}{'sup': '12', 'Rrepresents optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted aryl, or an optionally substituted cycloalkyl.'}4. The compound according to claim 1 , wherein Ris unsubstituted or substituted with one or more substituents selected from halogen claim 1 , cyano claim 1 , oxo claim 1 , nitro claim 1 , hydroxyl claim 1 , —SR claim 1 , —C-Calkyl claim ...

INHIBITORS OF HISTONE DEACETYLASE

The present invention relates to compounds of formula (I): 5. The compound of or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , or prodrug thereof claim 4 , wherein Ris selected from phenyl claim 4 , 2-pyridinyl claim 4 , 3-pyridinyl claim 4 , 4-pyridinyl claim 4 , 2-pyrimidinyl claim 4 , 4-pyrimidinyl claim 4 , 5-pyrimidinyl claim 4 , 2-pyrazinyl claim 4 , oxazolyl claim 4 , thiazolyl claim 4 , and isoxazolyl.12. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.13. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition wherein said condition is associated with histone deacetylase activity in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.14. The method of claim 13 , wherein the condition is selected from a neurological disorder claim 13 , memory loss or impairment claim 13 , cognitive function disorder or impairment claim 13 , extinction learning disorder claim 13 , fungal disease or infection claim 13 , inflammatory disease claim 13 , hematological disease claim 13 , and neoplastic disease.15. The method of claim 14 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress ...

Novel 3-(4(benzyloxy)phenyl)hex-4-inoic acid derivative, method of preparing same and pharmaceutical composition for preventing and treating metabolic disease including same as effective ingredient

The present invention relates to a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, a preparation method thereof, and a pharmaceutical composition comprising the same as an active ingredient for the prevention and treatment of metabolic disease. The novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention has excellent activities of activating GPR40 protein and promoting insulin secretion accordingly but has no toxicity when co-administered with other drugs. That is, the novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention can be co-administered with other drugs and can promote the activation of GPR40 protein significantly, so that the composition comprising the same as an active ingredient can be efficiently used as a pharmaceutical composition for the prevention and treatment of metabolic disease such as obesity, type I diabetes, type II diabetes, incompatible glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X, etc.

Triple reuptake inhibitors and methods of their use

Provided herein are bicyclic compounds and methods of synthesis thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various neurological disorders. Compounds provided herein inhibit re-uptake of endogenous monoamines, such as dopamine, serotonin and norepinephrine (e.g., from the synaptic cleft) and modulate one or more monoamine transporter. Pharmaceutical formulations containing the compounds are also provided.

Ether compounds for treatment of complement mediated disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R 12 or R 13 on the A group is an ether (R 32 ) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein Ror Ron the A group is an aryl, heteroaryl or heterocycle (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 2. The process of claim 1 , wherein Rand R are independently chosen from hydrogen claim 1 , halogen claim 1 , and C-Calkyl.3. The process of claim 1 , wherein Ris hydrogen.5. The process of claim 1 , wherein Ris hydrogen.6. The process of claim 1 , wherein B is —(C-Calkyl)(aryl) or —(C-Calkyl)(heteroaryl); each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 1 , and 0 or 1 substituents chosen from Rand R.7. The process of claim 1 , wherein B is —(C-Calkyl)(heteroaryl) which is unsubstituted or substituted with one or more substituents independently chosen from Rand R.8. The process of claim 1 , wherein Ris selected from halogen and C-Calkyl.14. The process of claim 13 , wherein Rand R are independently chosen from hydrogen claim 13 , halogen claim 13 , and C-Calkyl.15. The process of claim 14 , wherein Ris C-Calkanoyl.16. The process of claim 15 , wherein B is —(C-Calkyl)(heteroaryl); each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R.17. The process of claim 16 , wherein Ris hydrogen.18. The process of claim 17 , wherein Ris selected from halogen and C-Calkyl. This application is a continuation of U.S ...

CAPSAZEPINE ANALOGS FOR THE TREATMENT OF CANCER AND OTHER PROLIFERATIVE DISEASES

The present disclosure relates generally to derivatives of capsazepine and methods of use thereof. In some aspects, the present disclosure relates to using capsazepine derivatives to treat cancer or other hyperproliferative diseases. 2. The method of claim 1 , wherein Xis O.3. The method of claim 1 , wherein Xis S.4. The method according to claim 1 , wherein Ris —NRR claim 1 , wherein: Ris hydrogen claim 1 , alkyl claim 1 , substituted alkyl; and Ris aralkylor substituted aralkyl.512-. (canceled)1443-. (canceled)44. The method according to claim 1 , wherein Ris substituted aralkyl.4546-. (canceled)48. The method according to claim 1 , wherein the cancer is a carcinoma claim 1 , sarcoma claim 1 , lymphoma claim 1 , leukemia claim 1 , melanoma claim 1 , mesothelioma claim 1 , multiple myeloma claim 1 , or seminoma.49. The method according to claim 1 , wherein the cancer is of the bladder claim 1 , blood claim 1 , bone claim 1 , brain claim 1 , breast claim 1 , central nervous system claim 1 , cervix claim 1 , colon claim 1 , endometrium claim 1 , esophagus claim 1 , gall bladder claim 1 , gastrointestinal tract claim 1 , genitalia claim 1 , genitourinary tract claim 1 , head claim 1 , kidney claim 1 , larynx claim 1 , liver claim 1 , lung claim 1 , muscle tissue claim 1 , neck claim 1 , oral or nasal mucosa claim 1 , ovary claim 1 , pancreas claim 1 , prostate claim 1 , skin claim 1 , spleen claim 1 , small intestine claim 1 , large intestine claim 1 , stomach claim 1 , testicle claim 1 , or thyroid.5055-. (canceled)56. The method according to claim 1 , wherein the cancer is a solid tumor.57. The method according to claim 1 , wherein the method comprises injecting the compound directly into the tumor.58. (canceled)59. The method according to claim 1 , wherein the method comprises administering the compound systemically.60. (canceled)61. The method according to claim 1 , wherein the method further comprises alleviating pain.62. The method according to claim 1 , wherein ...

Nampt Inhibitors

Disclosed are compounds which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed. 2. A composition for treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis claim 1 , inflammatory bowel disease claim 1 , asthma and COPD (chronic obstructive pulmonary disease) claim 1 , osteoarthritis claim 1 , osteoporosis and fibrotic diseases; dermatosis claim 1 , including psoriasis claim 1 , atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis claim 1 , multiple sclerosis claim 1 , psoriatic arthritis claim 1 , ankylosing spondylitis claim 1 , tissue and organ rejection claim 1 , Alzheimer's disease claim 1 , stroke claim 1 , athersclerosis claim 1 , restenosis claim 1 , diabetes claim 1 , glomerulonephritis claim 1 , cancer claim 1 , particularly wherein the cancer is selected from breast claim 1 , prostate claim 1 , lung claim 1 , colon claim 1 , cervix claim 1 , ovary claim 1 , skin claim 1 , CNS claim 1 , bladder claim 1 , pancreas claim 1 , leukemia claim 1 , lymphoma or Hodgkin's disease claim 1 , cachexia claim 1 , inflammation associated with infection and certain viral infections claim 1 , including Acquired Immune Deficiency Syndrome (AIDS) claim 1 , adult respiratory distress syndrome claim 1 , and ataxia telengiectasia claim 1 , said composition comprising an excipient and a therapeutically effective amount of a compound of claim 1 , or pharmaceutically acceptable salts thereof.3. A method of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis claim 1 , inflammatory bowel disease claim 1 , asthma and COPD (chronic obstructive pulmonary disease) claim 1 , osteoarthritis claim 1 , osteoporosis and fibrotic diseases; dermatosis claim 1 , including psoriasis claim 1 , atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic ...

Compounds for treatment of complement mediated disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

AMIDE DERIVATIVES AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PREPARATION METHOD THEREOF AND MEDICINAL APPLICATION THEREOF

Amide derivatives and pharmaceutically acceptable salts thereof, preparation method thereof and medicinal application thereof are provided. Specifically, amide derivatives represented by general formula (I) are provided. The amide derivatives represented by general formula (I) can be used as a therapeutic agent, particularly as an inhibitor for microsomal prostaglandin E synthase-1 (mPGES-1), and also to treat and/or prevent diseases or illnesses such as inflammation and/or pain etc. The definition of each substituent group in general formula (I) is the same as the definition in the description. 6. The compound of formula (I) claim 1 , or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or pharmaceutically acceptable salt thereof according to claim 1 , wherein A claim 1 , B and Y are —CH—.7. The compound of formula (I) claim 1 , or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or pharmaceutically acceptable salt thereof according to claim 1 , wherein one of A claim 1 , B and Y is N claim 1 , the other two are —CH—.9. The compound of formula (I) claim 1 , or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris selected from the group consisting of alkyl and haloalkyl.15. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) claim 1 , or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent or excipient.1618.-. (canceled)19. The compound of formula (I) claim 1 , or the tautomer claim 1 , ...

Novel CYP34A-Specific Inhibitors and Methods of Using Same

The present invention includes novel compositions inhibiting CYP3A4. The present invention further includes a novel method of inhibiting CYP3A4 in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of the invention. In one embodiment, the subject is further administered at least one additional therapeutic agent. 2. The compound of claim 1 , wherein Ris selected from the group consisting of H claim 1 , benzyl claim 1 , and aniline.3. The compound of claim 1 , wherein Ris selected from the group consisting of H claim 1 , -(C-C)alkylene-carbocyclic claim 1 , -(C-C)alkylene-phenyl claim 1 , -(C-C)alkylene-substituted phenyl claim 1 , -(C-C)alkylene-heteroaryl claim 1 , or -(C-C)alkylene-substituted heteroaryl.4. The compound of claim 1 , wherein Ris -C-Calkyl.5. The compound of claim 1 , wherein m is 1.6. The compound of claim 1 , wherein n is 1.7. The compound of claim 1 , wherein X is S.10. A composition comprising a compound of .11. The composition of claim 10 , wherein the composition further comprises a pharmaceutically acceptable carrier.13. The method of claim 12 , wherein Ris selected from the group consisting of H claim 12 , benzyl claim 12 , and aniline.14. The method of claim 12 , wherein Ris selected from the group consisting of H claim 12 , -(C-C)alkylene-carbocyclic claim 12 , -(C-C)alkylene-phenyl claim 12 , -(C-C)alkylene-substituted phenyl claim 12 , -(C-C)alkylene-heteroaryl claim 12 , or -(C-C)alkylene-substituted heteroaryl.15. The method of claim 12 , wherein Ris -C-Calkyl.16. The method of claim 12 , wherein m is 1.17. The method of claim 12 , wherein n is 1.18. The method of claim 12 , wherein X is S.20. The method of claim 12 , wherein the method further comprises administering to the subject at least one additional therapeutic agent.21. The method of claim 20 , wherein the therapeutic agent is an antiviral agent.22. The method of claim 20 , wherein the composition and the additional ...

METHOD FOR PRODUCING FLUOROVINYL AMIDE COMPOUND

An object of this disclosure provides a novel method for producing a fluorovinyl amide compound and the like. The object is achieved by a method for producing a compound represented by formula (1): 2. The production method according to claim 1 , wherein Rf is —F or perfluoroalkyl.3. The production method according to claim 1 , wherein Ris —H claim 1 , an alkyl group optionally substituted with one or more substituents claim 1 , or an aromatic ring group optionally substituted with one or more substituents.4. The production method according to claim 1 , wherein Ris —H claim 1 , an alkyl group optionally substituted with one or more substituents claim 1 , or an aromatic ring group optionally substituted with one or more substituents.5. The production method according to claim 1 , wherein either Ror Ris —H claim 1 , and the other is —H or an aromatic ring group optionally substituted with one or more substituents.6. The production method according to claim 1 , wherein Ris a halo group or a sulfonic acid ester group.7. The production method according to claim 1 ,wherein{'sup': ['b1', 'b', 'h'], 'claim-text': ['wherein', {'sup': 'h', '#text': 'Ris'}, 'an aliphatic hydrocarbyl group optionally substituted with one or more substituents,', 'wherein one or more heteroatoms selected from the group consisting of O, S, and Si may be inserted into the aliphatic hydrocarbyl group, or', 'an aromatic ring group optionally substituted with one or more substituents, and', {'sup': ['b', 'r', 'r'], '#text': 'Lis a single bond, —NR—, —O—, or —S—, and Ris —H or an alkyl group.'}], '#text': 'Ris -L-R,'}8. The production method according to claim 1 ,wherein{'sup': ['b2', 'b', 'h'], 'claim-text': ['wherein', {'sup': 'h', '#text': 'Ris'}, 'an aliphatic hydrocarbyl group optionally substituted with one or more substituents,', 'wherein one or more heteroatoms selected from the group consisting of O, S, and Si may be inserted into the aliphatic hydrocarbyl group, or', 'an aromatic ring group ...

PREPARATION AND APPLICATION OF CLASS OF N-CONTAINING HETEROCYCLIC COMPOUNDS HAVING IMMUNOREGULATORY FUNCTION

The present invention discloses the preparation and application of heterocyclic compound having immunoregulatory function. Specifically, the present invention discloses a compound having a structure according to Formula I, wherein the definition of each group is as described in the specification. The invention also provides the use of the compounds in regulating immunity and inhibiting PD-1/PD-L1. 7. A pharmaceutical composition claim 1 , comprising (1) the compounds of or stereoisomers or tautomers thereof claim 1 , or pharmaceutically acceptable salts claim 1 , hydrates or solvates thereof; and (2) a pharmaceutically acceptable carrier.810-. (canceled)12. A method for treating diseases related to the activity or expression of PD-1/PD-L1 claim 1 , wherein the diseases are selected from the group consisting of tumors claim 1 , pathogen infections claim 1 , and diseases related to autoimmune responses; the method comprises:{'claim-ref': [{'@idref': 'CLM-00001', 'claim 1'}, {'@idref': 'CLM-00007', 'claim 7'}], 'administrating the compounds of or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts, hydrates or solvates thereof, or the pharmaceutical composition of to a subject in need thereof.'}13. The method of claim 12 , wherein the tumor is selected from the group consisting of melanoma claim 12 , renal cancer claim 12 , prostate cancer claim 12 , breast cancer claim 12 , colon cancer and lung cancer claim 12 , bone cancer claim 12 , pancreatic cancer claim 12 , skin cancer claim 12 , head or neck cancer claim 12 , skin or intraocular melanoma claim 12 , uterine cancer claim 12 , ovarian cancer claim 12 , rectal cancer claim 12 , anal cancer claim 12 , gastrointestinal cancer claim 12 , testicular cancer claim 12 , uterine cancer claim 12 , fallopian tube cancer claim 12 , endometrial cancer claim 12 , cervical cancer claim 12 , vaginal cancer claim 12 , vulva cancer claim 12 , Hodgkin's disease claim 12 , non-Hodgkin's lymphoma claim 12 , ...

Hydroxybenzamide Derivatives And Their Use As Inhibitors Of HSP90

The invention provides compounds of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R 1 is hydroxy or hydrogen; R 2 is hydroxy; methoxy or hydrogen; provided that at least one of R 1 and R 2 is hydroxy; R 3 is selected from hydrogen; halogen; cyano; optionally substituted C 1-5 hydrocarbyl and optionally substituted C 1-5 hydrocarbyloxy; R 4 is selected from hydrogen; a group —(O) n —R 7 where n is 0 or 1 and R 7 is an optionally substituted acyclic C 1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C 1-5 hydrocarbyl-amino; or R 3 and R 4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR 5 R 6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The compounds have activity as Hsp90 inhibitors.

Thalidomide analogs and methods of use

Thalidomide analogs and methods of using the thalidomide analogs are disclosed. Some embodiments of the disclosed compounds exhibit anti-angiogenic and/or anti-inflammatory activity. Certain embodiments of the disclosed compounds are non-teratogenic.

TETRACYCLINE COMPOUNDS

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

Compounds for preparing pyrrole six-membered heteroaryl ring derivative

Intermediate compounds used in the preparation of pyrrole six-membered heteroaryl ring derivatives are disclosed. In particular, compounds of formula (IB) are disclosed. The compounds of formula (IB) are used in the synthesis of Janus kinase (JAK) inhibitors. Substituents in formula (IB) have the same definitions as in the description.

ALPHA-CINNAMIDE COMPOUNDS AND COMPOSITIONS AS HDAC8 INHIBITORS

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

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein Ror Ron the A group is an ether (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 7. The compound of claim 6 , wherein Ris hydrogen claim 6 , and wherein B is —(C-Calkyl)(heteroaryl) or —(C-Calkyl)(biphenyl) each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 6 , and 0 or 1 substituents chosen from Rand R.8. The compound of claim 7 , wherein B is substituted with 0 substituents chosen from Rand R.9. The compound of claim 8 , wherein B is substituted with 0 substituents chosen from R.10. The compound of claim 9 , wherein B is aryl claim 9 , heteroaryl claim 9 , or biphenyl.11. The compound of claim 10 , wherein Ris halogen.16. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier.17. The pharmaceutical composition of claim 16 , wherein the composition is suitable for systemic delivery.18. The pharmaceutical composition of claim 16 , wherein the composition is suitable for topical delivery.19. The pharmaceutical composition of claim 16 , wherein the composition is suitable for ocular delivery.20. The pharmaceutical composition of claim 16 , wherein the composition is suitable for intravitreal delivery. This application is a continuation of U.S. patent ...

Novel RAD51 Inhibitors and Uses Thereof

The present invention includes novel RAD51 inhibitors. The compounds of the invention may be useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention. 2. The compound of claim 1 , wherein the compound is a compound of formula (I).3. The compound of claim 1 , wherein the compound is a compound of formula (II).4. The compound of claim 1 , wherein the compound is a compound of formula (III).5. The compound of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , and Rare each H.6. The compound of claim 3 , wherein R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , and Rare each H.7. The compound of claim 3 , wherein Ris selected from the group consisting of H claim 3 , F claim 3 , and CF.8. The compound of claim 3 , wherein Ris selected from the group consisting of H claim 3 , F claim 3 , and CF.9. The compound of claim 3 , wherein Ris selected from the group consisting of H claim 3 , F claim 3 , and CF.10. The compound of claim 4 , wherein R claim 4 , R claim 4 , R claim 4 , R claim 4 , R claim 4 , R claim 4 , R claim 4 , Rand Rare each H.11. The compound of claim 1 , wherein Het is selected from the group consisting of indolyl claim 1 , azaindolyl claim 1 , and thiazolyl claim 1 , wherein the indolyl claim 1 , azaindolyl claim 1 , or thiazolyl group may be optionally substituted.13. The compound of claim 12 , wherein Xis S.14. The compound of claim 12 , wherein Xis NR.15. The compound of claim 12 , wherein Xis NR.16. The compound of claim 12 , wherein Xis NR.17. The compound of claim 12 , wherein Xis NR.19. The compound of claim 2 , wherein p is 1.20. The compound of claim 3 , wherein q is 1.21. The compound of claim 4 , wherein r is 1.24. A ...

Materials for Organic Electroluminescent Devices

The present invention relates to a compound of formula (I) or (II), which is suitable for use as functional material in an electronic device, in particular as emitter material in an organic electroluminescent device. 115-. (canceled)17. The compound of claim 16 , wherein a+b=1 claim 16 , c+d=1 claim 16 , and e+f=1 or 2.18. The compound of claim 16 , wherein X is selected from C(R) claim 16 , Si(R) claim 16 , O claim 16 , or S.19. The compound of claim 16 , wherein E is claim 16 , on each occurrence claim 16 , identically or differently claim 16 , a divalent bridge selected from the group consisting of C(R) claim 16 , Si(R) claim 16 , O claim 16 , S claim 16 , and N(R) claim 16 , more preferably C(R).20. The compound of claim 16 , wherein E is C(R).21. The compound of claim 16 , wherein V is CR.25. An oligomer claim 16 , polymer claim 16 , or dendrimer comprising one or more compounds of claim 16 , wherein the bond(s) to the polymer claim 16 , oligomer claim 16 , or dendrimer are optionally localised at any desired position(s) in formula (I) or (II) which are substituted by R claim 16 , R claim 16 , or R.26. A formulation comprising at least one compound of and at least one solvent.27. A formulation comprising at least one polymer claim 25 , oligomer claim 25 , or dendrimer of and at least one solvent.28. An electronic device comprising at least one compound of claim 16 , wherein the electronic device is selected from the group consisting of organic integrated circuits claim 16 , organic field-effect transistors claim 16 , organic thin-film transistors claim 16 , organic light-emitting transistors claim 16 , organic solar cells claim 16 , organic optical detectors claim 16 , organic photoreceptors claim 16 , organic field-quench devices claim 16 , organic light-emitting electrochemical cells claim 16 , organic laser diodes claim 16 , and organic electroluminescent devices.29. The electronic device of claim 28 , wherein the electronic device is an organic ...

AMIDO COMPOUNDS AS RORyT MODULATORS AND USES THEREOF

Amido compounds are disclosed that have a formula represented by the following: and wherein Cy 1 , Cy 2 , n1, n2, R 1a , R 1b , R 2 , R 3 , R 4 , R 5 , and R 6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.

ALPHA-CINNAMIDE COMPOUNDS AND COMPOSITIONS AS HDAC8 INHIBITORS

The present invention relates to inhibitors of histone deacetylases, in particular HDAC8, that are useful for the treatment of cancer and other diseases and disorders, as well as the synthesis and applications of said inhibitors. 139-. (canceled)41. The method of claim 40 , wherein Rand Rare combined to form a heterocycle claim 40 , wherein said heterocycle is optionally substituted with one or more R.42. The method of claim 41 , wherein Ris at least one of hydrogen claim 41 , C-Calkyl claim 41 , oxo claim 41 , or C-Ccycloalkyl.43. The method of claim 41 , wherein Ris at least one of hydrogen claim 41 , oxo claim 41 , C-Ccycloalkyl claim 41 , or two Rwhen attached to the same carbon atom can form a C-Cspirocycle or a 3- to 12-membered spiroheterocycle.44. The method of claim 40 , wherein Ris aryl claim 40 , optionally substituted with one or more R.45. The method of claim 44 , wherein Ris —OR.46. The method of claim 40 , wherein the compound is (E)-N-(2-(3-(hydroxyamino)-3-oxoprop-1-en-1-yl)phenyl)-2-phenoxybenzamide claim 40 , or a pharmaceutically acceptable salt thereof.47. The method according to claim 40 , wherein the disease or disorder associated with HDAC8 inhibition is cancer claim 40 , neurological disease claim 40 , inflammatory disease claim 40 , autoimmune disease claim 40 , infection claim 40 , metabolic disease claim 40 , hematological disease claim 40 , or cardiovascular disease.48. The method according to claim 47 , wherein the cancer is colon cancer claim 47 , lung cancer claim 47 , neuroblastoma claim 47 , ovarian cancer claim 47 , hepatocellular carcinoma claim 47 , gastric cancer claim 47 , prostate cancer claim 47 , pancreatic cancer claim 47 , renal cancer claim 47 , cervical cancer claim 47 , ovarian cancer claim 47 , head and neck cancer claim 47 , lymphoma claim 47 , colorectal cancer claim 47 , non-small cell lung carcinoma claim 47 , breast cancer claim 47 , bladder cancer claim 47 , acute myeloid leukemia claim 47 , acute lymphoblastic ...

NOVEL POLYMORPHIC FORMS OF PERINDOPRIL (L)-ARGININE AND PROCESS FOR THE PREPARATION THEREOF

The present invention relates to novel and stable polymorphic forms of Perindopril (L)-Arginine designated as Form γ and amorphous form and processes for their preparation. The present invention also provides the novel polymorph Form γ with greater stability to heat and humidity and can be prepared on large scale by an efficient, economic and reproducible process. 1. Amorphous form of Perindopril (L)-Arginine.2. The amorphous form of Perindopril (L)-Arginine according to claim 1 , having a powder X-ray diffraction pattern as shown in .3. The amorphous form of Perindopril (L)-Arginine according to characterized by a glass transition temperature (Tg) at about 96° C. in DSC as shown in .4. A process for the preparation of amorphous Perindopril (L)-Arginine comprising the steps of:a) dissolving polymorphic form γ of Perindopril (L)-Arginine in a solvent,b) removing the solvent andc) isolating the amorphous Perindopril (L)-Arginine.5. The process according to claim 4 , wherein the solvent is an alcohol.6. The process according to claim 4 , wherein the solvent is methanol.7. The process according to claim 4 , wherein the solvent is removed by distillation.8. A process for the preparation of amorphous Perindopril (L)-Arginine comprising the steps of:a) suspending Perindopril free acid in a solvent or mixture of solvents,b) adding (L)-Arginine and heating the reaction mass to reflux temperature,c) cooling the solution to 20-30° C. andd) removing the solvent and isolating amorphous Perindopril (L)-Arginine.9. The process according to claim 8 , wherein the solvent is selected from the group consisting of lower alcohols claim 8 , dichloromethane claim 8 , water and mixtures thereof.10. The process according to claim 9 , wherein the lower alcohol is selected from the group consisting of methanol claim 9 , ethanol and isopropyl alcohol.11. The process according to claim 8 , wherein the solvent is removed by spray drying or by freeze drying.12. A process for the preparation of ...

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.

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein Ror Ron the A group is an aryl, heteroaryl or heterocycle (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 6. The compound of claim 1 , wherein B is (C-Calkyl)(aryl) or (C-Calkyl)(heteroaryl) each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 1 , and 0 or 1 substituents chosen from Rand R.7. The compound of claim 6 , wherein Ris halogen.8. The compound of claim 6 , wherein B is 2-pyridine.12. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.13. A method for the treatment of a disorder mediated by complement factor D claim 1 , comprising administering an effective amount to a host in need thereof of a compound of or a pharmaceutically acceptable salt thereof claim 1 , optionally in a pharmaceutically acceptable carrier.14. The method of claim 13 , wherein the host is a human.15. The method of claim 14 , wherein the disorder is age-related macular degeneration (AMD) or retinal degeneration.16. The method of claim 14 , wherein the disorder is an ophthalmic disease.17. The method of claim 14 , wherein the disorder is paroxysmal nocturnal hemoglobinuria (PNH).18. The method of claim 14 , wherein the disorder is multiple sclerosis claim 14 , arthritis claim 14 , a respiratory ...

GUANIDINE COMPOUNDS AND USE THEREOF

The present invention relates to guanidine compounds for inhibiting mitochondrial oxidative phosphorylation (OXPHOS) and use thereof. More specifically, the present invention relates to a pharmaceutical composition for preventing or treating a OXPHOS-related disease, particularly cancer, by inhibiting mitochondrial oxidative phosphorylation and reprogramming cellular metabolism. 120-. (canceled)23. The compound of claim 22 , wherein each of R claim 22 , Rand Ris hydrogen in chemical formula 2.25. The compound of claim 24 , wherein each of R claim 24 , Rand Ris hydrogen in chemical formula 3.27. The compound of claim 25 , wherein each of R claim 25 , Rand Ris hydrogen in chemical formula 4.29. The compound of claim 28 , wherein each of R claim 28 , Rand Ris hydrogen in chemical formula 5.30. The compound of claim 21 , wherein each of Rand Ris hydrogen in chemical formula 6.31. A compound selected from the group consisting of the following compounds claim 21 , and pharmaceutically acceptable salts claim 21 , pharmaceutically acceptable solvates claim 21 , prodrug forms of claim 21 , and derivatives of claim 21 , such compounds:N-1-(3,4-dichloro)phenethylbiguanide,N-1-(2,5-dichloro)phenethylbiguanide,N-1-(2-chloro)phenethylbiguanide,N-1-(2,4-dichloro)phenethylbiguanide,N-1-(3-fluoro)phenethylbiguanide,N-1-(4-trifluoromethoxy)phenethylbiguanide,N-1-(4-trifluoromethyl)phenethylbiguanide,N-1-(3-methoxy)phenethylbiguanide,N-1-(2-fluoro)phenethylbiguanide,N-1-(4-methyl)phenethylbiguanide,N-1-(4-methanesulphoneamine)phenethylbiguanide,N-1-(4-(N,N-dimethyl)phenethylbiguanide,N-1-(4-phenoxy)phenethylbiguanide,N-1-(4-isopropyl)phenethylbiguanide,N-1-(3,4-dimethyl)phenethylbiguanide,N-1-(2,4-dimethyl)phenethylbiguanide,N-1-(4-fluoro-2-methyl)phenethylbiguanide,N-1-(2,4-dimethyl)benzylbiguanide,N-1-(4-fluoro-3-methoxy)phenethylbiguanide,N-1-(3,4-difluoro)phenethylbiguanide,N-1-(2-morpholinoethyl)biguanide,N-1-(2-methyl)phenethylbiguanide,N-1-(3-bromo-4-fluoro)benzylbiguanide,N-1 ...

TETRACYCLINE COMPOUNDS

The present invention is directed to a compound represented by Structural Formula (I): 3. The compound of claim 1 , wherein:{'sup': 1a', '2', '3, 'Y is selected from fluoro, methyl, and —CH(R)—N(R)(R);'}{'sup': '1a', 'Ris selected from hydrogen and methyl;'}{'sup': '2', 'sub': 1', '3', '2, 'Ris selected from hydrogen, C-Cstraight chained alkyl and —CH-cyclopropyl;'}{'sup': 3', '3', '2', '3, 'sub': 1', '8', '2', '2', '1', '6', '1', '3', '3', '10', '2', '2', '3', '10', '1', '3', '1', '3', '1', '2, 'Ris selected from hydrogen, C-Calkyl, —CH—CHF, —C-Calkylene-O—C-Calkyl, C-Ccycloalkyl, —(CH)-phenyl and C-Ccycloalkyl-substituted C-Calkyl, wherein each cycloalkyl in the group represented by Ris optionally substituted with —C-Calkyl or optionally benzofused and when Ris hydrogen or —C-Calkyl, Ris additionally selected from benzyl; or'}{'sup': 2', '3, 'sub': 1', '3', '1', '3', '1', '3, 'Rand Rtaken together with the nitrogen atom to which they are bound form a ring selected from pyrrolidine and piperidine, wherein the ring is optionally substituted with one or more substituents independently selected from fluoro —C-Calkyl and —C-Calkylene-O—C-Calkyl, and wherein the ring is optionally fused to phenyl or spirofused to cyclopropyl.'}4. The compound of claim 1 , wherein at least one of X and Z is other than hydrogen.5. The compound of claim 4 , wherein both X and Z are other than hydrogen.6. The compound of claim 4 , wherein one of X and Z is hydrogen.7. The compound of claim 6 , wherein:{'sub': 3', '2, 'X is selected from hydrogen, fluoro, chloro, —CN, and —N(CH); and'}{'sub': 2', '2', '2', '3', '3, 'Z is hydrogen, NHor —CH—NH—CH—C(CH).'}9. The compound of claim 8 , wherein X is fluoro claim 8 , chloro or —N(CH).16. The compound of claim 1 , wherein:{'sup': '3', 'Y is —NHR, and'}{'sup': 3', '3, 'sub': 1', '8', '1', '3', '1', '3', '1', '3, 'Ris pyridyl, C-Calkyl, —C(O)—C-Calkylene-piperidine, —C(O)—C-Calkylene-pyrrolidine, wherein each piperidine or pyrrolidine in the group ...

Histone deacetylase inhibitors and compositions and methods of use thereof

Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use.

ISOINDOLINE COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE

Isoindoline sigma-2 receptor antagonist compounds, pharmaceutical compositions comprising such compounds, and methods for inhibiting Abeta-associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology are provided. 39. The compound of wherein{'sub': 3', '4', '5', '6', '2', '2', '1', '6', '1', '6', '1', '6', '1', '6', '2', '1', '4', '2', '3', '7', '1', '4', '2', 'n', 'n', '2', 'n', '1', '4', '2', '1', '4', '1', '4', '3', '2', '3', '3', '6', '1', '6', '1', '6', '1', '4', '1', '4', '2', '1', '6', '2', '7, 'each R, R, R, and Ris independently selected from the group consisting of H, OCHCHOH, O(C-Calkyl)OH, C-Chydroxyalkyl, C-CalkoxyC-Calkyl, aryl, heteroaryl, heterocycloalkyl, alkylaryl, heteroaryl, COR′, C(O)R′, N(C-Calkyl), NH(C-Ccycloalkyl), NHC(O)(C-Calkyl), CONR′, NC(O)R′, NS(O)R′, S(O)NR′, S(O)R′, C(O)O(C-Calkyl), OC(O)N(R′), C(O)(C-Calkyl), and C(O)NH(C-Calkyl); each n is independently 0, 1, or 2; each R′ is independently selected from the group consisting of H, CH, CHCH, C-Calkyl, C-Chaloalkyl, or optionally substituted aryl, alkylaryl, piperazin-1-yl, piperidin-1-yl, morpholinyl, heterocycloalkyl, heteroaryl, C-Calkoxy, NH(C-Calkyl), and N(C-Calkyl), wherein the optionally substituted group is selected from C-Calkyl or C-Cacyl.'}40. The compound of wherein each of R claim 38 , R claim 38 , R claim 38 , and Ris independently selected from the group consisting of H claim 38 , COR′ claim 38 , C(O)R′ claim 38 , CONR′ claim 38 , and S(O)R′; each n is independently 0 claim 38 , 1 claim 38 , or 2; and each R′ if present in R claim 38 , R claim 38 , R claim 38 , and Ris independently selected from the group consisting of H claim 38 , CH claim 38 , CHCH claim 38 , C-Calkyl claim 38 , C-Chaloalkyl claim 38 , or optionally substituted aryl claim 38 , alkylaryl claim 38 , piperazin-1-yl claim 38 , piperidin-1-yl claim 38 , ...

NOVEL COMPOUNDS

The present specification provides a compound of formula (I): 115-. (canceled)16. A composition comprising 2-acetyl-N-[4-(1 ,1 ,1 ,3 ,3 ,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-(methylsulfonyl)-2 ,3-dihydro-1H-isoindole-1-carboxamide , or a pharmaceutically acceptable salt thereof , wherein the composition is enantiomerically enriched for (1R)-2-acetyl-N-[4-(1 ,1 ,1 ,3 ,3 ,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-(methylsulfonyl)-2 ,3-dihydro-1H-isoindole-1-carboxamide.17. The composition of claim 16 , wherein the composition comprises enantiomerically enriched 2-acetyl-N-[4-(1 claim 16 ,1 claim 16 ,1 claim 16 ,3 claim 16 ,3 claim 16 ,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-(methylsulfonyl)-2 claim 16 ,3-dihydro-1H-isoindole-1-carboxamide.18. The composition of claim 16 , wherein the composition comprises a pharmaceutically acceptable salt of enantiomerically enriched 2-acetyl-N-[4-(1 claim 16 ,1 claim 16 ,1 claim 16 ,3 claim 16 ,3 claim 16 ,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-(methylsulfonyl)-2 claim 16 ,3-dihydro-1H-isoindole-1-carboxamide.19. The composition of claim 17 , wherein (1R)-2-acetyl-N-[4-(1 claim 17 ,1 claim 17 ,1 claim 17 ,3 claim 17 ,3 claim 17 ,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-(methylsulfonyl)-2 claim 17 ,3-dihydro-1H-isoindole-1-carboxamide is present in an enantiomeric excess of at least about 95%.20. The composition of claim 17 , wherein (1R)-2-acetyl-N-[4-(1 claim 17 ,1 claim 17 ,1 claim 17 ,3 claim 17 ,3 claim 17 ,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-(methylsulfonyl)-2 claim 17 ,3-dihydro-1H-isoindole-1-carboxamide is present in an enantiomeric excess of at least about 98%.21. The composition of claim 17 , wherein (1R)-2-acetyl-N-[4-(1 claim 17 ,1 claim 17 ,1 claim 17 ,3 claim 17 ,3 claim 17 ,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-(methylsulfonyl)-2 claim 17 ,3-dihydro-1H-isoindole-1-carboxamide is present in an enantiomeric excess of at least about 99%.22. The composition of claim 17 , wherein (1R)-2- ...

Phosphonate compounds for treatment of complement mediated disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is a phosphonate (R32) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

Fluoroallylamine Derivative And Use Thereof

The present invention relates to a fluoroallylamine derivative and use thereof. In particular, the present invention relates to a compound as shown in Formula I, a prodrug, an isomer, an isotope-labeled compound, a solvate or a pharmaceutically acceptable salt thereof, which has VAP-1/SSAO inhibitory activity, and can be used for treating a disease associated with VAP-1/SSAO overactivity. 8. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , an ester claim 1 , a solvate claim 1 , a hydrate claim 1 , an isomer claim 1 , or an isotope-labeled compound thereof; any crystal form or racemate thereof; a metabolite thereof; or a mixture thereof claim 1 , wherein the pharmaceutically acceptable salt is a hydrochloride or a trifluoroacetate claim 1 , and preferably claim 1 , the pharmaceutically acceptable salt is a hydrochloride.11. A pharmaceutical composition claim 1 , comprising a compound of claim 1 , a pharmaceutically acceptable salt claim 1 , an ester claim 1 , a solvate claim 1 , a hydrate claim 1 , an isomer claim 1 , or an isotope-labeled compound thereof; any crystal form or racemate thereof; a metabolite thereof; or a mixture thereof claim 1 , and one or more pharmaceutical excipients.1314.-. (canceled)15. A method for treating a disease or disorder associated with the overactivity of VAP-1/SSAO claim 1 , comprising a step of administrating a patient in need of such treatment with an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , an ester claim 1 , a hydrate claim 1 , a solvate claim 1 , an isomer claim 1 , or an isotope-labeled compound thereof; any crystal form or racemate thereof; a metabolite thereof; or a mixture thereof.16. The compound of claim 4 , or a pharmaceutically acceptable salt claim 4 , an ester claim 4 , a solvate claim 4 , a hydrate claim 4 , an isomer claim 4 , or an isotope-labeled compound thereof; any crystal form or racemate thereof; a metabolite thereof; or a mixture ...

Chemical Compounds as ATF-4 Pathway Inhibitors

The invention is directed to substituted bridged cycloalkane derivatives. Specifically, the invention is directed to compounds according to Formula IIIQ: 8. A pharmaceutical composition comprising the compound according to or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.9. A method of treating a disease selected from: cancer claim 1 , pre-cancerous syndromes claim 1 , Alzheimer's disease claim 1 , spinal cord injury claim 1 , traumatic brain injury claim 1 , ischemic stroke claim 1 , stroke claim 1 , diabetes claim 1 , Parkinson disease claim 1 , Huntington's disease claim 1 , Creutzfeldt-Jakob Disease claim 1 , prion diseases claim 1 , progressive supranuclear palsy claim 1 , amyotrophic lateral sclerosis claim 1 , myocardial infarction claim 1 , cardiovascular disease claim 1 , inflammation claim 1 , fibrosis claim 1 , chronic and acute diseases of the liver claim 1 , chronic and acute diseases of the lung claim 1 , chronic and acute diseases of the kidney claim 1 , chronic traumatic encephalopathy (CTE) claim 1 , neurodegeneration claim 1 , dementia claim 1 , cognitive impairment claim 1 , atherosclerosis claim 1 , ocular diseases claim 1 , neurological disorders claim 1 , pain claim 1 , in organ transplantation and arrhythmias claim 1 , in a human in need thereof claim 1 , which comprises administering to such human a therapeutically effective amount of the compound as described in or a pharmaceutically acceptable salt thereof.10. (canceled)11. A method of treating a disease selected from: cancer claim 7 , pre-cancerous syndromes claim 7 , Alzheimer's disease claim 7 , spinal cord injury claim 7 , traumatic brain injury claim 7 , ischemic stroke claim 7 , stroke claim 7 , diabetes claim 7 , Parkinson disease claim 7 , Huntington's disease claim 7 , Creutzfeldt-Jakob Disease claim 7 , and related prion diseases claim 7 , progressive supranuclear palsy claim 7 , amyotrophic lateral sclerosis claim 7 , myocardial infarction ...

Inhibitors of receptor interacting protein kinase i for the treatment of disease

Disclosed herein are compounds which inhibit RIPK1, pharmaceutical compositions, and methods of treatment of RIPK1-mediated diseases, such as neurodegenerative disorders, inflammatory disorders, and cancer.

Compounds, pharmaceutical composition and their use in treating neurodegenerative diseases

The present invention is directed to novel compounds of Formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.

INTERMEDIATE COMPOUNDS AND PROCESS FOR THE PREPARATION OF LURASIDONE AND SALTS THEREOF

The present invention relates to a process for the preparation of Lurasidone or a pharmaceutically acceptable salt thereof, a compound useful for the treatment of schizophrenia and bipolar disorder. The present invention further relates to processes for the preparation of Lurasidone intermediates, and to certain novel intermediates obtained by such processes. 128-. (canceled)31. The process according to claim 29 , further comprising the step of converting the compound of formula (1) or (1′) to its pharmaceutically acceptable salt.32. The process according to claim 31 , wherein the compound is Lurasidone HCl.33. The process according to claim 29 , wherein X is O; Y and Y′ are independently selected from OH and NH; and Y″ is OH.35. The process according to claim 29 , wherein X is NH; Y and Y′ together are N(CHCHOH)and Y″ is N(CHCHOH).37. The process according to claim 29 , wherein Y″ is N(CHCHOSOR)or N(CHCHHal)and Y′″ is NH.40. The process according to claim 29 , wherein Y″ is OSOR; and Y′″ is piperazinyl.43. The process according to claim 42 , wherein in step (a) the sulfonating reagent is selected from an alkylsulfonyl chloride claim 42 , an arylsulfonyl chloride and anhydride derivatives thereof.44. The process according to claim 42 , wherein in step (c) the ammonia derivative is ammonium carbonate or monoprotected ammonia derivatives selected from Boc-NH claim 42 , Bzl-NH claim 42 , and Ac-NH. The present invention relates to a process for the preparation of (3aR,4S,7R,7aS)-2-[((1R,2R)-2-{[4-(1,2-benzisothiazol-3-yl)-piperazin-1-yl]methyl}cyclohexyl)methyl]hexahydro-1H-4,7-methanisoindol-1,3-dione (Lurasidone) and salts thereof, a compound useful for the treatment of schizophrenia and bipolar disorder. The present invention further relates to processes for the preparation of Lurasidone intermediates, and to certain novel intermediates obtained by such processes.Lurasidone hydrochloride (SM-13,496) is an atypical antipsychotic marketed by Dainippon Sumitomo Pharma ...

INHIBITORS OF HISTONE DEACETYLASE

The present invention relates to compounds of formula (I): 10. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.11. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.12. The method of claim 11 , wherein the condition is selected from a neurological disorder claim 11 , memory loss or impairment claim 11 , cognitive function disorder or impairment claim 11 , extinction learning disorder claim 11 , fungal disease or infection claim 11 , inflammatory disease claim 11 , hematological disease claim 11 , and neoplastic disease.13. The method of claim 11 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, phobia, social anxiety disorder, substance dependence recovery or Age Associated Memory Impairment (AAMI), or Age Related Cognitive Decline (ARCD);a hematological disease selected from acute myeloid leukemia, acute promyelocytic leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, myelodysplastic syndromes, and sickle cell anemia;a cancer; andan extinction learning disorder selected from a fear extinction deficit and post-traumatic ...

Isoindolone derivatives

The present invention provides for compounds of formula (I) wherein A, Y, J, R 1 , R 2 , and R 3 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof,that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, diabetes, obesity, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).

Compounds, pharmaceutical composition and their use in treating neurodegenerative diseases

The present invention is directed to novel compounds of Formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.

COMPOUNDS FOR TREATMENT OF CARDIAC ARRHYTHMIAS AND HEART FAILURE

This disclosure concerns compounds and a method for modulating the activity of calcium ion channels, including Ca-induced (or Ca-activated) calcium release channels and conformationally coupled calcium release channels such as ryanodine receptors. Some of the compounds have a structure according to formula I, or a stereoisomer, tautomer, hydrate, solvate, prodrug, or pharmaceutically acceptable salt thereof. 2. The compound according to claim 1 , wherein Ris —Y—X—(CR)—N(R)R.4. The compound according to claim 3 , wherein the compound has a structure according to Formula II claim 3 , and X is N(R) where Ris aliphatic.5. The compound according to claim 3 , wherein the compound has a structure according to formula III claim 3 , and Y is an imidazolyl claim 3 , pyrazolyl claim 3 , triazolyl claim 3 , tetrazolyl claim 3 , oxazolyl claim 3 , isoxazolyl claim 3 , oxadiazolyl claim 3 , furazanyl claim 3 , thiazolyl claim 3 , isothiazolyl claim 3 , or thiadiazolyl group.6. (canceled)7. The compound according to claim 5 , wherein Y is a tetrazolyl or oxadiazolyl group.911-. (canceled)12. The compound according to claim 1 , wherein:{'sup': 4', '5, '(i) Rand Rare alkyl; or'}(ii) m is 2, or n is 1, or m is 2 and n is 1; or{'sup': 6', '7', '6', '7, '(iii) Ris H, or each Ris H, or Ris H and each Ris H; or'}(iv) any combination thereof.1318-. (canceled)19. The compound according to claim 1 , wherein:{'sup': A', '1', '2', '1', '2, 'Ris —N(R)Rwhere Ris H or aliphatic and Ris H or aliphatic;'}{'sup': 'B', 'Ris H, aliphatic, —O-aliphatic, —S-aliphatic, —O—C(O)-aliphatic, or halogen;'}{'sup': 'C', 'Ris H, aliphatic, —S-aliphatic, or —O—C(O)-aliphatic; and'}{'sup': 'D', 'sub': 2', 'q', '2', '2', 'q', '2', 'q', '3, 'Ris —(CH)NH, —(CH)OH, or —(CH)SOM where q is an integer from 1 to 10 and M is a monatomic cation.'}2022-. (canceled)23. The compound according to claim 1 , wherein the compound is:{'sup': 1', '2', '2, 'N-(4-amino-2-methoxybenzyl)-N,N-diethylethane-1,2-diamine;'}3-methoxy-4-(((2 ...

Process for the Manufacture of Non-Steroidal Anti-Inflammatory Agents and Intermediates Thereof

The current invention describes novel chiral synthetic routes and intermediates for the manufacture of chiral anti-inflammatory agents of general formula VIII 118.-. (canceled)22. A process according to claim 21 , wherein the compound of formula I is reacted with SO/pyridine complex to form the aldehyde of formula V.23. A process according to claim 20 , wherein claim 20 , in producing the compound of formula VII the compound of formula V is dissolved in acetic acid claim 20 , the amine of formula VI is added at room temperature claim 20 , toluene is added and the mixture is refluxed for 5-50 h to yield the imine of formula VII.24. A process according to claim 20 , wherein the amine of formula VI is:1-amino-2-methyl-benzene1-amino-4-methyl-benzene2-amino-4-methylpyridine2-amino-pyridine2-amino-pyrimidine3-amino-quinoline4-amino-pyridine4-amino-pyrimidine5-amino-isoquinoline5-amino-1-methyl-isoquinoline5-amino-2,6-di-methylquinoline5-amino-2-methyl-indole5-amino-2-methyl-isoquinol-1(2H)-one5-amino-2-methylquinoline5-amino-6-chloro-2-methylquinoline5-amino-6-fluoro-2-methylquinoline5-amino-isoquinol-2(1H)-one5-amino-quinolineamino-benzene orN-(4-aminophenyl)-piperidine25. A process according to claim 24 , wherein the amine of formula VI is 5-amino-2-methylquinoline.26. A process according to claim 19 , wherein the imine of formula VII is reacted with sodium borohydride in alcoholic solution to yield the compound according to formula VIII.27. A process according to claim 19 , wherein the compound of formula VIII is:1,1,1 trifluoro-4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-4-methyl-2-{[(2-methyl-5-quinoline-5-ylimino]methyl}pentane-2-ol).28. A process according to claim 19 , wherein the compound of formula VIII is:1,1,1 trifluoro-4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-4-methyl-2-{[(2-methyl-5-quinolinyl]methyl}pentane-2-ol).30. A process according to claim 19 , wherein one of the groups X claim 19 , X claim 19 , Xis fluoro and the other groups X claim 19 , X claim 19 , ...

ISOINDOLINE INHIBITORS OF ROR-GAMMA

Provided are novel compounds of Formula (I): 7. The compound of claim 6 , wherein Ris (C-C)alkyl.8. The compound of claim 7 , wherein Cyis selected from aryl claim 7 , monocyclic cycloalkyl claim 7 , monocyclic heterocyclyl claim 7 , and bicyclic heterocyclyl claim 7 , each of which is optionally substituted with 1 to 2 groups independently selected from R.9. The compound of claim 8 , wherein Cyis phenyl claim 8 , cyclohexyl claim 8 , dioxanyl claim 8 , tetrahydropyranyl or 4 claim 8 ,5 claim 8 ,6 claim 8 ,7-tetrahydrobenzo[d]oxazolyl claim 8 , each of which are optionally substituted with 1 to 2 groups independently selected from R.10. The compound of claim 9 , wherein Cyis phenyl claim 9 , piperidinyl claim 9 , or pyridinyl claim 9 , each of which is optionally substituted with 1 to 2 groups independently selected from R.11. The compound of claim 10 , wherein{'sup': 1', '5, 'Cyis phenyl or pyridinyl, each of which is optionally substituted with 1 to 2 groups independently selected from R; and'}{'sup': 2', '6, 'Cyis cyclohexyl or phenyl, each of which is optionally substituted with 1 to 2 groups independently selected from R.'}12. The compound of claim 11 , wherein Ris hydrogen; and Ris hydrogen claim 11 , hydroxy(C-C)alkyl claim 11 , (C-C)alkoxy(C-C)alkyl claim 11 , aminocarbonyl-O(C-C)alkyl claim 11 , hydroxycarbonyl(C-C)alkoxy(C-C)alkyl claim 11 , (C-C)alkylcarbonylamino(C-C)alkyl claim 11 , (C-C)alkoxycarbonylamino(C-C)alkyl claim 11 , di(C-C)alkylamino(C-C)alkyl claim 11 , di(C-C)alkylaminocarbonyl(C-C)alkyl claim 11 , (C-C)alkylaminocarbonyl(C-C)alkyl claim 11 , aminocarbonyl(C-C)alkyl claim 11 , or aminocarbonyl.13. The compound of claim 12 , wherein Ris hydrogen; and Ris hydrogen claim 12 , —CHOH claim 12 , —(CH)OH claim 12 , —CHOCH claim 12 , —CHOC(O)NH claim 12 , —CHOCHCOOH claim 12 , —CHNHC(O)CH claim 12 , —CHNHC(O)OCH claim 12 , —(CH)N(CH) claim 12 , —CHC(O)N(CH) claim 12 , —CHC(O)NHCH claim 12 , —CHC(O)NH claim 12 , or CONH.14. The compound of claim 13 ...

NOVEL COMPOUNDS

The present specification provides a compound of formula (I): 2. A compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', '4, 'sub': '1-6', 'Ris (CO)Ror (CO)NH—Calkyl;'}{'sup': '2', 'sub': 1-6', '2, 'Ris Calkyl or CH-cyclopropyl;'}{'sup': '3', 'sub': '1-6', 'Ris Calkoxy, CN or heterocycloalkyl; and'}{'sup': '4', 'claim-text': [{'sub': '1-6', 'Calkyl optionally substituted with OH; or'}, {'sub': '1-6', 'Calkoxy.'}], 'Ris3. A compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris (CO)R.4. A compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris unsubstituted Calkyl.5. A compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris unsubstituted Calkyl.6. A compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris CN.7. A compound according to selected from:N-[4-(2-Cyano-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]-5-(methylsulfonyl)-2,3-dihydro-1H-isoindole-1-carboxamide;2-Acetyl-N-[4-(2-cyano-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]-5-(methylsulfonyl)-2,3-dihydro-1H-isoindole-1-carboxamide;N-[4-(2-Cyano-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]-2-[(1-methoxycyclopropyl)carbonyl]-5-(methylsulfonyl)-2,3-dihydro-1H-isoindole-1-carboxamide;{'sup': '2', 'N-[4-(2-Cyano-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]-N-methyl-5-(methylsulfonyl)-1,3-dihydro-2H-isoindole-1,2-dicarboxamide;'}N-[4-(2-Cyano-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]-2-(hydroxyacetyl)-5-(methylsulfonyl)-2,3-dihydro-1H-isoindole-1-carboxamide;N-[4-(2-Cyano-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]-2-formyl-5-(methylsulfonyl)-2,3-dihydro-1H-isoindole-1-carboxamide;Methyl 1-{[4-(2-cyano-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]carbamoyl}-5-(methylsulfonyl)-1,3-dihydro-2H-isoindole-2-carboxylate;N-[4-(2-Cyano-1,1,1,3, ...

Preparation and use of compounds as protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Q is a bond or —N(R 5 )—; T is a bond, —O—, —C(O)—; S, —N(R 5 )—, or —C(R 6′ R 7′ ); U is a bond or —C(R 6 )(R 7 )— Y is C or N; Z is C or N; ring A, including variables Y and Z, is a three to nine membered cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl, and heteroaryl ring having 0 to 4, preferably 0 to 2, heteroatoms independently selected from the group consisting of O, S, N and —N(R)—, wherein ring A is unsubstituted or substituted with 1 to 5 independently selected R 1 moieties and/or oxo when ring A is cycloalkyl, cycloalkenyl, heterocyclyl or heterocyclenyl; and R, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 6 , R 7 and R 7′ are as defined in the specification; pharmaceutical compositions comprising the compounds of formula I and the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases.

METHOD FOR PROVIDING STABLE ISOINDOLE DERIVATIVES

Method for producing an isoindole derivative, the isoindole derivative obtainable by the methods, a methods for stabilizing an isoindole derivative, and methods for detection and/or quantification of macromolecules. 2. The method according to claim 1 , wherein the electron deficient π-system is selected from the group consisting of pyridine claim 1 , pyrimidine claim 1 , benzoic acid claim 1 , benzonitrile claim 1 , (1 claim 1 ,1′ claim 1 ,1″-trifluoromethyl)benzene claim 1 , benzeneboronic acid claim 1 , nitrobenzene claim 1 , chlorobenzene claim 1 , quinoline claim 1 , isoquinoline claim 1 , naphthyridine claim 1 , the electron neutral π-system is benzene or naphthalene claim 1 , and the electron rich π-system is selected from the group consisting of toluene claim 1 , thiophene claim 1 , phenol claim 1 , furan claim 1 , pyrrole claim 1 , N claim 1 ,N-dimethylaniline.3. The method according to claim 1 , wherein component I is an ortho-dialdehyde.4. The method according to claim 1 , wherein Component I is selected from the group consisting of 2 claim 1 ,3-pyridinedicarboxyaldehyde claim 1 , 3 claim 1 ,4-diformyl-benzoic acid claim 1 , 2-acetylthiophene-3-carboxyaldehyde claim 1 , and 4-(2-formylquinoline-3-carbonyl)benzoic acid.5. The method according to claim 1 , wherein the macromolecule as Component II has at least four amino groups.6. The method according to claim 1 , wherein the component II is selected from the group consisting of polylysine claim 1 , poly(amidoamine) dendrimers claim 1 , polypropylene imine dendrimers claim 1 , poly(melamine) dendrimers claim 1 , peptides claim 1 , proteins claim 1 , and sugars.7. The method according to claim 1 , wherein the macromolecule as Component II is a dendrimer with at least four amino groups.8. The method according to claim 1 , wherein the thiol as Component III contains at least one thiol group and no primary amino group.9. The method according to claim 1 , wherein Component III is a thiol containing compound ...

PRMT5 INHIBITORS AND USES THEREOF

Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described. 1214-. (canceled)216227-. (canceled)231234-. (canceled)235. The compound of claim 215 , wherein Ris hydrogen.236. The compound of claim 215 , wherein n is 0.237. The compound of claim 215 , wherein n is 1.238258-. (canceled)260261-. (canceled)263278-. (canceled)279. The compound of claim 215 , wherein Lis a bond.280. The compound of claim 215 , wherein Lis an optionally substituted claim 215 , straight or branched claim 215 , Caliphatic chain wherein one methylene unit of Lis re laced by —N(R)—.281. The compound of claim 215 , wherein Cyis an optionally substituted 5- to 6-membered carbocyclic ring.282283-. (canceled)284. The compound of claim 215 , wherein Cyis an optionally substituted 9- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen claim 215 , oxygen claim 215 , and sulfur.285. The compound of claim 284 , wherein Cyis optionally substituted indazole claim 284 , optionally substituted quinoline claim 284 , optionally substituted benzimidazole claim 284 , optionally substituted benzothiazole claim 284 , optionally substituted deazapurine claim 284 , optionally substituted indole claim 284 , optionally substituted purine claim 284 , optionally substituted pyrazolopyridine claim 284 , optionally substituted pyrrolopyridine claim 284 , optionally substituted pyrrolopyrimidine claim 284 , optionally substituted imidazopyridine claim 284 , or optionally substituted imidazopyridine.287. A pharmaceutical composition comprising a compound of claim 215 , or a pharmaceutically acceptable salt thereof claim 215 , and a pharmaceutically acceptable excipient.288. A kit or packaged pharmaceutical comprising a compound of claim 215 , or a ...

Targeted nitroxide agents

Provided herein are compositions and related methods useful for free radical scavenging, with particular selectivity for mitochondria. The compounds comprise a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. Also provided herein are methods, for preventing, mitigating and treating damage caused by radiation. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation.

Hydrobenzamide derivatives as inhibitors of hsp90

The invention provides an acid addition salt of a compound of the formula ( 1 ). Also provided by the invention are processes for preparing the compound of formula ( 1 ) and alkyl analogues thereof, novel intermediates for use in the process and methods for preparing the intermediates. The invention also provides new medical uses of compounds of the formula ( 1 ) and its ethyl analogue.

CYCLOPROPYL-AMIDE COMPOUNDS AS DUAL LSD1/HDAC INHIBITORS

The present disclosure describes novel compounds of the general Formula (I), their analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites, and prodrugs thereof. These compounds can inhibit both LSD and HDAC and are useful as therapeutic or ameliorating agent for diseases that are involved in cellular growth such as malignant tumors, schizophrenia, Alzheimer's disease, parkinson's disease and the like. 133-. (canceled)35. The method of claim 34 , wherein the condition is mediated by both LSD1 and HDAC1.36. The method of claim 34 , wherein the condition is mediated by both LSD1 and HDAC6.37. The method of claim 34 , wherein the condition is mediated by HDAC.38. The method of claim 34 , wherein the condition is a proliferative disorder or cancer.39. The method of claim 34 , wherein the condition is cancer.40. The method of claim 39 , wherein the cancer is breast cancer claim 39 , prostate cancer claim 39 , pancreatic cancer claim 39 , gastric cancer claim 39 , lung cancer claim 39 , colon cancer claim 39 , rectal cancer claim 39 , esophagus cancer claim 39 , duodenal cancer claim 39 , tongue cancer claim 39 , pharyngeal cancer claim 39 , brain tumor claim 39 , neurinoma claim 39 , non-small cell lung cancer claim 39 , small cell lung cancer claim 39 , liver cancer claim 39 , kidney cancer claim 39 , bile duct cancer claim 39 , uterine body cancer claim 39 , cervical cancer claim 39 , ovarian cancer claim 39 , urinary & bladder cancer claim 39 , skin cancer claim 39 , hemangioma claim 39 , malignant lymphoma claim 39 , malignant melanoma claim 39 , thyroid cancer claim 39 , bone tumor claim 39 , vascular fibroma claim 39 , retinoblastoma claim 39 , penile cancer claim 39 , pediatric solid cancer claim 39 , Myelodysplastic syndrome (MDS) claim 39 , lymphoma claim 39 , myeloma claim 39 , leukemia claim 39 , acute myelogenous leukemia (AML) claim 39 , chronic myelogenous leukemia ...

Isoindoline compositions and methods for treating neurodegenerative disease

Isoindoline sigma-2 receptor antagonist compounds, pharmaceutical compositions comprising such compounds, and methods for inhibiting Abeta-associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology are provided.

PRMT5 INHIBITORS AND USES THEREOF

Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described. 393-. (canceled)95100-. (canceled)102103-. (canceled)104. The compound of claim 94 , wherein Ris hydrogen.105. The compound of claim 94 , wherein n is 0 claim 94 , 1 or 2.106108-. (canceled)109. The compound of claim 94 , wherein Ar is heteroaryl.110112-. (canceled)113. The compound of claim 94 , wherein Ar is substituted with 1 or 2 Rgroups.114134-. (canceled)135. The compound of claim 94 , wherein at least one Ris —N(R).136149-. (canceled)151214-. (canceled)216285-. (canceled)287. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable excipient.288. A kit or packaged pharmaceutical comprising a compound of or a pharmaceutically acceptable salt thereof claim 1 , and instructions for use thereof.289293-. (canceled)2941. A method of treating a PRMT5-mediated disorder claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim or a pharmaceutically acceptable salt thereof.295. (canceled)296. The method of claim 294 , wherein the disorder is cancer a metabolic disorder claim 294 , or a blood disorder.297. The method of claim 296 , wherein the cancer is hematopoietic cancer claim 296 , lung cancer claim 296 , prostate cancer claim 296 , melanoma claim 296 , or pancreatic cancer.298. (canceled)299. The method of claim 296 , wherein the metabolic disorder is diabetes or obesity.300301-. (canceled)302. The method of claim 296 , wherein the blood disorder is a hemoglobinopathy.303. The method of claim 302 , wherein the blood disorder is sickle cell anemia or β-thalessemia.304. (canceled) This application claims priority under 35 U.S.C ...

Amino compounds for treatment of complement mediated disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein R12 or R13 on the A group is an amino substituent (R32) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

TRIPLE REUPTAKE INHIBITORS AND METHODS OF THEIR USE

Provided herein are bicyclic compounds and methods of synthesis thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various neurological disorders. Compounds provided herein inhibit reuptake of endogenous monoamines, such as dopamine, serotonin and norepinephrine (e.g., from the synaptic cleft) and modulate one or more monoamine transporter. Pharmaceutical formulations containing the compounds are also provided. 2. The compound of claim 1 , wherein m and n are both 1.3. The compound of claim 1 , wherein m is 2 and n is 1.4. The compound of claim 1 , wherein X is hydrogen.5. The compound of claim 1 , wherein X is (C-C)alkyl.6. The compound of claim 5 , wherein X is methyl or ethyl.7. The compound of claim 1 , wherein Y and Z are both halogen.8. The compound of claim 7 , wherein Y and Z are both chloride.9. The compound of claim 1 , wherein the compound is stereomerically pure.11. A pharmaceutical composition comprising a compound of .12. The pharmaceutical composition of claim 11 , which further comprises one or more additional active agents.13. A method of inhibiting binding of a monoamine transporter ligand to a monoamine transporter claim 1 , said method comprising contacting said monoamine transporter and a compound of .14. A method of inhibiting the activity of at least one monoamine transporter claim 1 , said method comprising contacting said monoamine transporter and a compound of .15. The method of or claim 1 , wherein said monoamine transporter is a serotonin transporter (SERT) claim 1 , a dopamine transporter (DAT) claim 1 , a norepinephrine transporter (NET) claim 1 , or a combination thereof.16. The method of claim 14 , wherein said compound inhibits the activity of at least two different monoamine transporters.17. A method of inhibiting uptake of at least one monoamine by a cell claim 1 , said method comprising contacting said cell and a compound of .18. The method of claim 17 , wherein said monoamine is ...

SUBSTITUTED TETRAHYDROCYCLOPENTA[C]PYRROLES, SUBSTITUTED DIHYDROPYRROLIZINES, ANALOGUES THEREOF, AND METHODS USING SAME

The present invention includes novel substituted bicyclic compounds, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infection and/or hepatitis D virus (HDV) infection in a patient. 2. The compound of claim 1 , wherein each occurrence of Ror Ris independently selected from the group consisting of —(CH)-(optionally substituted heteroaryl) claim 1 , —(CH)-(optionally substituted heterocyclyl) claim 1 , and —(CH)-(optionally substituted aryl).3. The compound of claim 1 , wherein each occurrence of optionally substituted alkyl claim 1 , optionally substituted alkenyl claim 1 , optionally substituted alkynyl claim 1 , optionally substituted heterocyclyl claim 1 , or optionally substituted cycloalkyl is independently optionally substituted with at least one substituent selected from the group consisting of C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , C-Ccycloalkyl claim 1 , halogen claim 1 , cyano claim 1 , —OR claim 1 , optionally substituted phenyl claim 1 , optionally substituted heteroaryl claim 1 , optionally substituted heterocyclyl claim 1 , —N(R)C(═O)R claim 1 , —C(═O)OH claim 1 , —C(═O)OR claim 1 , —C(═O)NRR claim 1 , and —N(R)(R) claim 1 , wherein each occurrence of Ris independently H claim 1 , optionally substituted C-Calkyl claim 1 , optionally substituted C-Ccycloalkyl claim 1 , optionally substituted aryl claim 1 , or optionally substituted heteroaryl claim 1 , or two Rgroups combine with the N to which they are bound to form a heterocycle.4. The compound of claim 1 , wherein each occurrence of optionally substituted aryl or optionally substituted heteroaryl is independently optionally substituted with at least one substituent selected from the group consisting of C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-Chaloalkoxy claim 1 , heterocyclyl claim 1 , halogen claim 1 , —CN claim 1 , —OR claim 1 , —N(R)(R) claim 1 , —NO claim 1 , —S(═O)N(R)(R) claim 1 , acyl claim 1 , and C-Calkoxycarbonyl ...

CYCLIC AMIDE DERIVATIVES AS INHIBITORS OF 11 - BETA - HYDROXYSTEROID DEHYDROGENASE AND USES THEREOF

The present invention relates to certain amide derivatives that have the ability to inhibit 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and which are therefore useful in the treatment of certain disorders that can be prevented or treated by inhibition of this enzyme. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders. It is expected that the compounds of the invention will find application in the treatment of conditions such as non-insulin dependent type 2 diabetes mellitus (NIDDM), insulin resistance, obesity, impaired fasting glucose, impaired glucose tolerance, lipid disorders such as dyslipidemia, hypertension and as well as other diseases and conditions. 221-. (canceled)22. Use of a compound according to in the preparation of a medicament.23. A use according to wherein the medicament is for treatment of a condition that can be prevented or treated by inhibition of 11β-HSD1.2430-. (canceled) The present invention relates to bicyclic heterocyclic amide derivatives that have the ability to inhibit 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and which are therefore useful in the treatment of certain disorders that can be prevented or treated by inhibition of this enzyme. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders. It is expected that the compounds of the invention will find application in the treatment of conditions such as non-insulin dependent type 2 diabetes mellitus (NIDDM), insulin resistance, obesity, impaired fasting glucose, impaired glucose tolerance, lipid disorders such as dyslipidemia, hypertension and as well as other diseases and conditions.Glucocorticoids are stress hormones with regulatory effects on carbohydrate, ...

ABHD6 AND DUAL ABHD6/MGL INHIBITORS AND THEIR USES

Provided herein are compounds and pharmaceutical compositions for selectively inhibiting serine hydrolase a/b-hydrolase domain 6 (ABHD6) and dually inhibiting ABHD6 and monoacylglycerol lipase (MGL). The compounds and pharmaceutical compositions disclosed herein are useful for treating a number of therapeutic conditions related to cannabinergic receptor function such as pain, inflammation, neuropathy, neurodegenerative diseases, anxiety disorders, motor function disorder, metabolic disorder, glaucoma and chemotherapy-induced nausea and vomiting and cancer. 3. The compound according to claim 2 , wherein E=O.4. The compound according to claim 1 , selected from the group consisting of:Example 11,1,1,3,3,3-Hexafluoropropan-2-yl 3,4-dihydroisoquinoline-2(1H)-carboxylateExample 21,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylateExample 31,1,1,3,3,3-Hexafluoropropan-2-yl (S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylateExample 41,1,1,3,3,3-Hexafluoropropan-2-yl 8-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylateExample 51,3-Difluoropropan-2-yl 5-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylateExample 61,1,1,3,3,3-Hexafluoropropan-2-yl 1-methyl-3,4-dihydroisoquinoline-2(1H)-carboxylateExample 71,1,1,3,3,3-Hexafluoropropan-2-yl 1-ethyl-3,4-dihydroisoquinoline-2(1H)-carboxylateExample 81,1,1,3,3,3-Hexafluoropropan-2-yl 5-bromoisoindoline-2-carboxylateExample 91,1,1,3,3,3-Hexafluoropropan-2-yl 5-methoxyisoindoline-2-carboxylateExample 101,1,1,3,3,3-Hexafluoropropan-2-yl 5-bromoindoline-1-carboxylateExample 111,1,1,3,3,3-Hexafluoropropan-2-yl 3-bromo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylateExample 121,1,1,3,3,3-Hexafluoropropan-2-yl 4-bromoisoindoline-2-carboxylateExample 131,1,1,3,3,3-Hexafluoropropan-2-yl 3-methyl-3,4-dihydroisoquinoline-2(1H)-carboxylateExample 141,1,1,3,3,3-Hexafluoropropan-2-yl-2-chloro-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylateExample 151,1,1,3,3,3-Hexafluoropropan-2-yl 5-bromo-1-methylisoindoline ...

METHOD FOR EXTRACTING ACTIVE INGREDIENTS

A method for extracting active ingredient(s) from a raw material to be extracted is provided. The method comprises the following steps: (1) mixing a raw material to be extracted with an aqueous solvent to provide a mixture; (2) conducting a homogenization to the mixture to obtain a first extract with active ingredient(s); and (3) conducting a high pressure homogenization to the first extract to obtain a second extract with active ingredient(s), wherein the homogenization in step (2) is conducted at a temperature ranging from normal temperature to 100° C. 1. A method for extracting an active ingredient from a raw material to be extracted , comprising the following steps:(1) mixing the raw material to be extracted with an aqueous solvent to provide a mixture;(2) conducting a homogenization of the mixture to obtain a first extract with the active ingredient; and(3) conducting a high pressure homogenization of the first extract to obtain a second extract with the active ingredient,wherein the homogenization in step (2) is conducted at a temperature ranging from normal temperature to 100° C.2. The method as claimed in claim 1 , wherein the high pressure homogenization in step (3) is conducted at a pressure ranging from 100 bar to 2 claim 1 ,000 bar.3. The method as claimed in claim 1 , wherein the homogenization in step (2) is conducted at a temperature ranging from normal temperature to 90° C.4Chenopodium formosanum. The method as claimed in claim 1 , wherein the raw material to be extracted is selected from the group consisting of claim 1 , black tomato claim 1 , banana peel and combinations thereof.5Chenopodium formosanum. The method as claimed in claim 4 , wherein the raw material to be extracted is claim 4 , and the active ingredient is selected from the group consisting of betalain claim 4 , betaxanthin claim 4 , polyphenol claim 4 , flavonoid and combinations thereof.6. The method as claimed in claim 5 , wherein the homogenization in step (2) is conducted at a ...

Small molecule compound and synthesizing method and uses thereof

Provided is a small molecule compound as represented by structural formula (I). The product of the present invention in various concentrations and dosages can achieve an obvious change in the growth period of hairs, promoting the growth of the hairs, thus exhibiting an obvious effect of promoting hair growth. In addition, changes in the weight of a mouse in each group are slow, indicating that the test compound does not cause weight loss in an animal.

TITANIUM (IV) COMPOUNDS AND METHODS OF FORMING HETEROCYCLIC COMPOUNDS USING SAME

The present disclosure provides Titanium (IV) compounds and methods of making heterocyclic compounds such as pyrroles using Titanium (IV) compounds. In certain embodiments, the Titanium (IV) compound is present in catalytic amounts. 2. The compound of wherein each Rindependently represents an alkyl group or an aryl group; each X independently represents an inorganic anionic ligand; and each L independently represents a neutral organic coordinating ligand.3. A method of forming a heterocyclic compound comprising:combining at least one compound having a triple bond, at least one azo compound, and at least one Ti(IV) compound under conditions effective for a [2+2+1] cycloaddition reaction to occur and form one or more heterocyclic compounds.5. The method of wherein each Rindependently represents an alkyl group or an aryl group; each X independently represents an inorganic anionic ligand; and each L independently represents a neutral organic coordinating ligand.6. The method of wherein the at least one azo compound is of the formula R—N═N—R claim 4 , wherein each Rindependently represents an organic group.7. The method of wherein each Rindependently represents an alkyl group or an aryl group.8. The method of wherein the at least one compound having a triple bond is at least one alkyne claim 4 , and the one or more heterocyclic compounds formed include one or more pyrroles.10. The method of wherein each Rindependently represents an alkyl group or an aryl group; and each Rand Rindependently represents hydrogen claim 9 , an alkyl group claim 9 , or an aryl group.12. The method of wherein each Rindependently represents an alkyl group or an aryl group; and each Rand Rindependently represents hydrogen claim 11 , an alkyl group claim 11 , or an aryl group.13. The method of wherein the at least one compound having a triple bond is at least one nitrile-functional compound claim 4 , and the one or more heterocyclic compounds formed include one or more triazoles.15. The method of ...

Acly inhibitors and uses thereof

The present invention provides compounds useful as inhibitors of ATP citrate lyase (ACLY), compositions thereof, and methods of using the same.

Novel Compounds

The present specification provides a compound of formula (I): 3. A compound of formula (II) according to claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein:{'sup': '2', 'sub': 1-6', '1-6', '2', '1-6, 'Ris Calkyl (optionally substituted with OH or Calkoxy) or CH-cyclopropyl (optionally substituted with halo, OH, CN or Calkoxy);'}{'sup': '3', 'Ris H;'}{'sup': 4', '7', '8, 'sub': 1-6', 'a', '3-7', '1-6', '1-6', '1-3', '1-6', '1-6, 'Ris Calkyl (optionally substituted with (R)), Ccycloalkyl (optionally substituted with halo, Calkyl, OH, CN, Calkoxy or Calkyl-OR), heterocycloalkyl (optionally substituted with Calkyl or OH) or Calkoxy;'}a is 1, 2 or 3;{'sup': 7', '9', '10', '11', '12, 'sub': 1-6', '3-7', '3-7', '1-6', '1-6, 'Ris independently selected from the group consisting of halo, OH, CN, Calkoxy, NRR, Ccycloalkyl, heterocycloalkyl and aryl, wherein said Ccycloalkyl, heterocycloalkyl or aryl groups are further optionally substituted with 1, 2 or 3 groups independently selected from the group consisting of Calkyl, CN, OH, Calkoxy and NRR; and'}{'sup': 8', '9', '10', '11', '12, 'sub': '1-6', 'R, R, R; Rand Rare each independently H or Calkyl.'}4. A compound of formula (II) according to claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Ris unsubstituted Calkyl or unsubstituted CH-cyclopropyl.5. A compound of formula (II) according to claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein:{'sup': '2', 'sub': 1-6', '2, 'Ris unsubstituted Calkyl or unsubstituted CH-cyclopropyl; and'}{'sup': 4', '7, 'sub': 1-6', 'a, 'Ris Calkyl (optionally substituted with (R)); and'}a is 1, 2 or 3;{'sup': 7', '9', '10', '11', '12, 'sub': 1-6', '3-7', '3-7', '1-6', '1-6, 'Ris independently selected from the group consisting of halo, OH, CN, Calkoxy, NRR; Ccycloalkyl, heterocycloalkyl and aryl, wherein said Ccycloalkyl, heterocycloalkyl or aryl groups are further optionally substituted with 1, 2 or 3 groups independently ...

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein Ror Ron the A group is an aryl, heteroaryl or heterocycle (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 6. The compound of claim 1 , wherein B is —(C-Calkyl)(aryl) or —(C-Calkyl)(heteroaryl) each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 1 , and 0 or 1 substituents chosen from Rand R.7. The compound of claim 6 , wherein Ris halogen.8. The compound of claim 6 , wherein B is 2-pyridine.12. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.13. A method for the treatment of a disorder mediated by complement factor D claim 1 , comprising administering an effective amount to a host in need thereof of a compound of or a pharmaceutically acceptable salt thereof claim 1 , optionally in a pharmaceutically acceptable carrier.14. The method of claim 13 , wherein the host is a human.15. The method of claim 14 , wherein the disorder is age-related macular degeneration (AMD).16. The method of claim 14 , wherein the disorder is retinal degeneration.17. The method of claim 14 , wherein the disorder is an ophthalmic disease.18. The method of claim 14 , wherein the disorder is paroxysymal nocturnal hemoglobinuria (PNH).19. The method of claim 14 , wherein the disorder is multiple ...

NOVEL COMPOUNDS

The present specification provides a compound of formula (I): 115-. (canceled)16. A method of treating a disease state in a human suffering from said disease state , which comprises administering to the human in need of such treatment a therapeutically effective amount of (1R)-2-acetyl-N-[4-(1 ,1 ,1 ,3 ,3 ,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-(methylsulfonyl)-2 ,3-dihydro-1H-isoindole-1-carboxamide , or a pharmaceutically acceptable salt thereof , and wherein the disease state is selected from ulcerative cholitis , Crohn's disease , multiple sclerosis , inflammatory bowel disease , rheumatoid arthritis , graft versus host disease , systemic lupus erythematosis , and lupus nephritis.17. The method of treating according to claim 16 , wherein the disease state is ulcerative cholitis.18. The method of treating according to claim 16 , wherein the disease state is Crohn's disease.19. The method of treating according to claim 16 , wherein the disease state is multiple sclerosis.20. The method of treating according to claim 16 , wherein the disease state is inflammatory bowel disease.21. The method of treating according to claim 16 , wherein the disease state is rheumatoid arthritis.22. The method of treating according to claim 16 , wherein the disease state is graft versus host disease.23. The method of treating according to claim 16 , wherein the disease state is systemic lupus erythematosis.24. The method of treating according to claim 16 , wherein the disease state is lupus nephritis. This application is a continuation of U.S. application Ser. No. 15/997,310, filed on Jun. 4, 2018, which is a continuation of U.S. application Ser. No. 15/378,360, filed on Dec. 14, 2016, which claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 62/267,391, filed on Dec. 15, 2015. All of the above listed applications are incorporated by reference herein in its entirety for all purposes.This application incorporates by reference a Sequence Listing ...

ARYL HYDROCARBON RECEPTOR ANTAGONISTS AND METHODS OF USE

The disclosure relates to aryl hydrocarbon receptor antagonists as well as methods of modulating aryl hydrocarbon receptor activity and expanding hematopoietic stem cells by culturing hematopoietic stem or progenitor cells in the presence of these agents. Additionally, the disclosure provides methods of treating various pathologies, such as cancer, by administration of these aryl hydrocarbon receptor antagonists. Additionally, the disclosure provides methods of treating various pathologies in a patient by administration of expanded hematopoietic stem cells. The disclosure further provides kits containing aryl hydrocarbon receptor antagonists that can be used for the expansion of hematopoietic stem cells. The disclosure further relates to pharmaceutical compositions comprising the compounds and methods of treating or preventing a disease in which aryl hydrocarbon receptor plays a role. 2. The compound of claim 1 , wherein b is 1 and c is 0.3. The compound of any one of the preceding claims claim 1 , wherein A is an optionally substituted monocyclic ring selected from the group consisting of benzene claim 1 , pyridine claim 1 , thiazole claim 1 , piperazine claim 1 , pyrimidine claim 1 , 1 claim 1 ,2 claim 1 ,3-triazole claim 1 , pyrazole claim 1 , furan claim 1 , isoxazole claim 1 , 4H-pyridazine claim 1 , thiophene claim 1 , oxazole claim 1 , and 2H-pyridine.4. The compound of any one of the preceding claims claim 1 , wherein A is an optionally substituted bicyclic ring selected from the group consisting of benzo[d][1 claim 1 ,2 claim 1 ,3]triazole claim 1 , thieno[2 claim 1 ,3-b]pyridine claim 1 , imidazo[1 claim 1 ,2-a]pyridine claim 1 , quinolone claim 1 , pyrido[1 claim 1 ,2-a]pyrimidine claim 1 , 6 claim 1 ,7-dihydro-5H-thiazolo[4 claim 1 ,5-b]pyridine claim 1 , benzo[d]imidazole claim 1 , isoindoline claim 1 , benzo[d]isothiazole claim 1 , benzo[d]thiazole claim 1 , benzo[b]thiophene claim 1 , indoline claim 1 , and [1 claim 1 ,2 claim 1 ,4]triazolo[1 claim 1 ...

TITANIUM (IV) COMPOUNDS AND METHODS OF FORMING HETEROCYCLIC COMPOUNDS USING SAME

The present disclosure provides Titanium (IV) compounds and methods of making heterocyclic compounds such as pyrroles using Titanium (IV) compounds. In certain embodiments, the Titanium (IV) compound is present in catalytic amounts. 2. The compound of wherein each Rindependently represents an alkyl group or an aryl group; each X independently represents an inorganic anionic ligand; and each L independently represents a neutral organic coordinating ligand.3. A method of forming a heterocyclic compound comprising:combining at least one compound having a triple bond, at least one azo compound, and at least one Ti(IV) compound under conditions effective for a [2+2+1] cycloaddition reaction to occur and form one or more heterocyclic compounds.5. The method of wherein each Rindependently represents an alkyl group or an aryl group; each X independently represents an inorganic anionic ligand; and each L independently represents a neutral organic coordinating ligand.6. The method of wherein the at least one azo compound is of the formula R—N═N—R claim 4 , wherein each Rindependently represents an organic group.7. The method of wherein each Rindependently represents an alkyl group or an aryl group.8. The method of wherein the at least one compound having a triple bond is at least one alkyne claim 4 , and the one or more heterocyclic compounds formed include one or more pyrroles.10. The method of wherein each Rindependently represents an alkyl group or an aryl group; and each Rand Rindependently represents hydrogen claim 9 , an alkyl group claim 9 , or an aryl group.12. The method of wherein each Rindependently represents an alkyl group or an aryl group; and each Rand Rindependently represents hydrogen claim 11 , an alkyl group claim 11 , or an aryl group.13. The method of wherein the at least one compound having a triple bond is at least one nitrile-functional compound claim 4 , and the one or more heterocyclic compounds formed include one or more triazoles.15. The method of ...

Polymorphic forms of st-246 and methods of preparation

Polymorph forms of 4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-ethenocycloprop[f]isoindol-2(1H)-yl)-benzamide are disclosed as well as their methods of synthesis and pharmaceutical compositions.

COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE

This invention relates to novel diarylamino compounds that bind to the sigma-2 receptor, to pharmaceutical compositions comprising such compounds, and to methods for inhibiting or restoring synapse loss in neuronal cells, modulating a membrane trafficking change in neuronal cells, and treating cognitive decline and neurodegenerative diseases and disorders therewith. 7. The compound of claim 6 , wherein{'sub': 1', '3, 'R=Cl, F, CF, or OH;'}{'sub': 2', '3', '1', '2, 'R=H, Cl, F, CF, or Rand Rare linked together to form a —O-ethylene-O-group;'}{'sub': 3', '3, 'R=CF; and'}{'sub': '4', 'R=methyl, and pharmaceutically acceptable salts thereof.'}17. A method/use for inhibiting an amyloid beta effect on a neuronal cell comprising administering an effective amount of a composition comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'A compound of in an amount effective to inhibit amyloid beta oligomer binding in said cell; and'}a pharmaceutically acceptable carrier.18. The method/use of claim 17 , wherein the compound is administered in an amount also effective to inhibit membrane trafficking deficits in said cell claim 17 , said membrane trafficking effects being associated with exposure of said cell to soluble amyloid beta oligomers.19. The method claim 17 , wherein the compound is in an amount effective to inhibit both the oligomer binding and synapse loss associated with exposure of the cell to soluble amyloid beta oligomer in said cell.20. The method of claim 17 , wherein the compound is administered in an amount effective to inhibit a soluble amyloid beta oligomer-mediated cognitive effect.21. (canceled)22. (canceled)23. (canceled)24. (canceled)25. The method/use of for inhibiting amyloid beta oligomer-induced synaptic dysfunction of a neuronal cell; comprising contacting the cell with the composition comprising a sigma-2 receptor antagonist compound in an amount effective to inhibit amyloid beta oligomer binding in said cell claim 17 , said dysfunction being ...

SUBSTITUTED UREAS AND METHODS OF MAKING AND USING SAME

The invention relates to substituted ureas, and compositions comprising the same, which in certain embodiments are useful for treating and/or preventing pain in a subject in need thereof. 10. The compound of claim 1 , wherein A is selected from the group consisting of isoindolin-2-yl claim 1 , 5-fluoroisoindolin-2-yl claim 1 , 5-chloroisoindolin-2-yl claim 1 , 5-methoxyisoindolin-2-yl claim 1 , 5-methylisoindolin-2-yl claim 1 , 5-hydroxyisoindolin-2-yl claim 1 , 5-cyanoisoindolin-2-yl claim 1 , 4-fluoroisoindolin-2-yl claim 1 , 4-chloroisoindolin-2-yl claim 1 , 4-methoxyisoindolin-2-yl claim 1 , 4-methylisoindolin-2-yl claim 1 , 4-hydroxyisoindolin-2-yl claim 1 , 4-cyanoisoindolin-2-yl claim 1 , 5 claim 1 ,6-difluoroisoindolin-2-yl claim 1 , 5 claim 1 ,6-dichloroisoindolin-2-yl claim 1 , 6-chloro-5-fluoroisoindolin-2-yl claim 1 , 5-chloro-6-fluoroisoindolin-2-yl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 5-fluoro-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 6-fluoro-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 7-fluoro-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 8-fluoro-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 5-hydroxy-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 6-hydroxy-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 7-hydroxy-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 8-hydroxy-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthalen-1-yl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthalen-2-yl claim 1 , 5-fluoro-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthalen-1-yl claim 1 , 6-fluoro-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthalen-1-yl claim 1 , 7-fluoro-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthalen-1-yl claim 1 , 8-fluoro-1 claim 1 ,2 claim 1 ,3 ...

SUBSTITUTED PHENOXYPROPYLCYCLOAMINE DERIVATIVES AS HISTAMINE-3 (H3) RECEPTOR LIGANDS

The present invention provides compounds of formula I: 133-. (canceled)35. The method of claim 34 , wherein in the compound X is O.36. The method of claim 34 , wherein in the compound X is NOR.37. The method of claim 34 , wherein in the compound Y is O and m is 3.38. The method of claim 34 , wherein in the compound X is O claim 34 , Y is O claim 34 , and m is 3.39. The method of claim 34 , wherein in the compound Ris a pyrrolidin-1-yl claim 34 , piperidin-1-yl claim 34 , piperazin-1-yl or morpholin-4-yl group claim 34 , wherein said groups are optionally substituted with 1 to 3 Rgroups.40. The method of claim 38 , wherein in the compound Ris a pyrrolidin-1-yl claim 38 , piperidin-1-yl claim 38 , piperazin-1-yl or morpholin-4-yl group claim 38 , wherein said groups are optionally substituted with 1 to 3 Rgroups.41. The method of claim 40 , wherein in the compound Ris a pyrrolidin-1-yl or piperidin-1-yl group claim 40 , wherein said groups are optionally substituted with 1 to 3 Rgroups.42. The method of claim 41 , wherein in the compound Ris 2-methyl-pyrrolidin-1-yl.43. The method of claim 34 , wherein in the compound A is pyrrolidin-1-yl claim 34 , piperidin-1-yl claim 34 , morpholin-4-yl claim 34 , piperazin-1-yl claim 34 , or thiomorpholin-4-yl wherein said groups are optionally substituted with 1 to 3 Rgroups.44. The method of claim 38 , wherein in the compound A is pyrrolidin-1-yl claim 38 , piperidin-1-yl claim 38 , morpholin-4-yl claim 38 , piperazin-1-yl claim 38 , or thiomorpholin-4-yl wherein said groups are optionally substituted with 1 to 3 Rgroups.45. The method of claim 36 , wherein in the compound Y is O claim 36 , m is 3 and A is pyrrolidin-1-yl claim 36 , piperidin-1-yl claim 36 , morpholin-4-yl claim 36 , or piperazin-1-yl.46. The method of claim 38 , wherein in the compound A is 3 claim 38 ,4-dihydro-1H-isoquinolin-2-yl; 1 claim 38 ,3-dihydro-isoindol-2-yl; 3 claim 38 ,4-dihydro-2H-quinolin-1-yl; 2 claim 38 ,3 claim 38 ,4 claim 38 ,5-tetrahydrobenzo ...

Compositions and Methods for Enhancing Proteasome Activity

Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

TRIPLE REUPTAKE INHIBITORS AND METHODS OF THEIR USE

Provided herein are bicyclic compounds and methods of synthesis thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various neurological disorders. Compounds provided herein inhibit reuptake of endogenous monoamines, such as dopamine, serotonin and norepinephrine (e.g., from the synaptic cleft) and modulate one or more monoamine transporter. Pharmaceutical formulations containing the compounds are also provided. 2. The compound of claim 1 , wherein m and n are both 1.3. The compound of claim 1 , wherein m is 2 and n is 1.4. The compound of claim 1 , wherein X is hydrogen.5. The compound of claim 1 , wherein X is (C-C)alkyl.6. The compound of claim 5 , wherein X is methyl or ethyl.7. The compound of claim 1 , wherein Y and Z are both halogen.8. The compound of claim 7 , wherein Y and Z are both chloride.9. The compound of claim 1 , wherein the compound is stereomerically pure.11. A pharmaceutical composition comprising a compound of .12. The pharmaceutical composition of claim 11 , which further comprises one or more additional active agents.13. A method of inhibiting binding of a monoamine transporter ligand to a monoamine transporter claim 1 , said method comprising contacting said monoamine transporter and a compound of .14. A method of inhibiting the activity of at least one monoamine transporter claim 1 , said method comprising contacting said monoamine transporter and a compound of .15. The method of or claim 1 , wherein said monoamine transporter is a serotonin transporter (SERT) claim 1 , a dopamine transporter (DAT) claim 1 , a norepinephrine transporter (NET) claim 1 , or a combination thereof.16. The method of claim 14 , wherein said compound inhibits the activity of at least two different monoamine transporters.17. A method of inhibiting uptake of at least one monoamine by a cell claim 1 , said method comprising contacting said cell and a compound of .18. The method of claim 17 , wherein said monoamine is ...

INHIBITORS OF HISTONE DEACETYLASE

The present invention relates to compounds of formula (I): 10. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.11. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.12. The method of claim 11 , wherein the condition is selected from a neurological disorder claim 11 , memory loss or impairment claim 11 , cognitive function disorder or impairment claim 11 , extinction learning disorder claim 11 , fungal disease or infection claim 11 , inflammatory disease claim 11 , hematological disease claim 11 , and neoplastic disease.13. The method of claim 11 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, phobia, social anxiety disorder, substance dependence recovery or Age Associated Memory Impairment (AAMI), or Age Related Cognitive Decline (ARCD);a hematological disease selected from acute myeloid leukemia, acute promyelocytic leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, myelodysplastic syndromes, and sickle cell anemia;a cancer; andan extinction learning disorder selected from a fear extinction deficit and post-traumatic ...

Thalidomide analogs

Thalidomide analogs that modulate tumor necrosis factor alpha (TNFα) activity and angiogenesis are disclosed. In particularly disclosed embodiments, the thalidomide analogs are isosteric sulfur-containing analogs. Also disclosed are methods of treating a subject with the analogs.

ISOINDOLINE COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE

Isoindoline sigma-2 receptor antagonist compounds, pharmaceutical compositions comprising such compounds, and methods for inhibiting Abeta-associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology are provided. 137.-. (canceled)40. The method of wherein the total daily dose is 10 to 300 mg.41. The method of wherein the total daily dose is 20 to 150 mg.42. The method of wherein the total daily dose is administered in a single dose.43. The method of wherein the total daily dose is administered in multiple doses per day.44. The method of wherein the compound is formulated in a capsule or tablet.45. The method of wherein the capsule or tablet comprises 10 to 200 mg of the compound or a pharmaceutically acceptable salt thereof.46. The method of wherein the wherein the total daily dose is 10 to 300 mg.47. The method of wherein the wherein the total daily dose is 20 to 150 mg.48. The method of wherein the compound is administered orally.51. The method of wherein the total daily dose of the compound administered is 10 to 300 mg.52. The method of wherein the total daily dose of the compound administered is 20 to 150 mg.53. The method of wherein the total daily dose is administered in a single dose.54. The method of wherein the total daily dose is administered in multiple doses per day.55. The method of wherein the pharmaceutical composition is a capsule or tablet.56. The method of wherein the capsule or tablet comprises 10 to 200 mg of the compound or a pharmaceutically acceptable salt thereof.57. The method of wherein the wherein the total daily dose is 10 to 300 mg.58. The method of wherein the wherein the total daily dose is 20 to 150 mg.59. The method of wherein the pharmaceutical composition is administered orally. This application is a continuation of U.S. patent application Ser. No. 15/700,923, filed Sep. 11, 2017, which ...

PYRROLE HETEROARYL RING DERIVATIVE AND METHOD OF USE THEREOF

A pyrrole six-membered heteroaryl ring derivative, and the medicinal uses thereof are described. Specifically, the pyrrole six-membered heteroaryl ring derivative is a compound of formula (I), wherein the variable groups are as described in the specification. 3. A method for the treatment of a disease or disorder claim 2 , comprising administering to a subject in need thereof the pharmaceutical composition according to claim 2 , wherein the disease or disorder is selected form the group consisting of allograft rejection; graft versus host disease; atopic dermatitis; rheumatoid arthritis; psoriasis; lymphoma; leukemia; pancreatic cancer; breast cancer; cutaneous T-cell lymphoma; and cutaneous B-cell lymphoma.7. The process according to claim 5 , wherein the alkaline condition of step (i) is provided by an organic base or an inorganic base.8. The process according to claim 7 , wherein the organic base is selected from the group consisting of triethylamine claim 7 , N claim 7 , N-diisopropylethylamine claim 7 , n-butyllithium claim 7 , tert-butyl potassium alkoxide claim 7 , and tetrabutylammonium bromide; and the inorganic base is selected from the group consisting of sodium hydride claim 7 , sodium carbonate claim 7 , sodium bicarbonate claim 7 , potassium carbonate claim 7 , potassium bicarbonate and cesium carbonate.9. The process according to claim 8 , wherein the alkaline condition of step (i) is provided by the organic base of triethylamine.10. The process according to claim 5 , wherein the t-butoxycarbonyl group of compound 5 is removed in step (ii) in the presence of hydrogen chloride.14. The process according to claim 12 , wherein the alkaline condition is provided by an organic base or an inorganic base.15. The process according to claim 14 , wherein the organic base is selected from the group consisting of triethylamine claim 14 , N claim 14 , N-diisopropylethylamine claim 14 , n-butyllithium claim 14 , tert-butyl potassium alkoxide claim 14 , and ...

Factor D Inhibitors Useful for Treating Inflammatory Disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 22. A pharmaceutical composition comprising a compound of claim 1 , together with a pharmaceutically acceptable carrier.23. A method of treating or preventing a complement D-related disorder comprising administering a therapeutically effective amount of a compound of claim 1 , to a patient in need of such treatment.24. The method of claim 23 , wherein the disorder is paroxysmal nocturnal hemoglobinuria.25. The method of claim 23 , wherein the disorder is age-related macular degeneration.26. The method of claim 23 , wherein the disorder is selected from inflammation of the eye claim 23 , retinal degeneration claim 23 , myasthenia gravis claim 23 , C3 glomerulonephritis claim 23 , abdominal aortic aneurysm claim 23 , or atypical hemolytic uremic syndrome. This application is a continuation of U.S. application Ser. No. 14/630,959, filed Feb. 25, 2015, which claims benefit of provisional U.S. Application No. 61/944,189 filed Feb. 25, 2014, provisional U.S. Application No. 62/022,916 filed Jul. 10, 2014, and provisional U.S. Application 62/046,783 filed Sep. 5, 2014. The entirety of each of these applications is hereby incorporated by reference for all purposes.Complement Factor D is part of the alternative pathway of the complement cascade and plays an early and central role in activating the ...

ISOINDOLINES AS HDAC INHIBITORS

The present disclosure relates to inhibitors of zinc-dependent histone deacetylases (HDACs), having the formula: (I) wherein Z, X, X, Y, Y, Y, L, Z, and R are described herein. 3. The compound of or , wherein one of Y , Y , and Yis N and the other two of Y , Y , and Yare CR.4. The compound of or , wherein two of Y , Y , and Yare N and the other one of Y , Y , and Yis CR.5. The compound of any one of - , wherein Y , Yand Yare each CR.6. The compound of any one of - , wherein L is a bond.7. The compound of any one of - , wherein L is —C(O)—.8. The compound of any one of - , wherein L is —(CRR)— , —C(O)NR— , —NRC(O)— , —C(O)(CRR)O— , or —(CRR)C(O)— , wherein p is 1 or 2.10. The compound of any one of - , wherein R is heterocyclyl , aryl , or heteroaryl containing 1-5 heteroatoms selected from the group consisting of N , S , P , or O , wherein each heterocyclyl , aryl , or heteroaryl is optionally substituted with one or more —OH , halogen , oxo , —NO , —CN , —R , —R , —SR , —OR , —NHR , —NRR , —S(O)NRR , —S(O)R , —C(O)R , —C(O)OR , —NRS(O)R , —S(O)R , —S(O)NRR , —NRS(O)R , heterocyclyl , aryl , or heteroaryl.11. The compound of any one of - , wherein R is heteroaryl containing 1-5 heteroatoms selected from the group consisting of N , S , P , or O , wherein the heteroaryl is optionally substituted with one or more —OH , halogen , oxo , —NO , —CN , —R , —R , —SR , —OR , —NHR , —NRR , —S(O)NRR , —S(O)R , —C(O)R , —C(O)OR , —NRS(O)R , —S(O)R , —S(O)NRR , —NRS(O)R , heterocyclyl , aryl , or heteroaryl.12. The compound of any one of - , wherein R is aryl containing 1-5 heteroatoms selected from the group consisting of N , S , P , or O , wherein the aryl is optionally substituted with one or more —OH , halogen , oxo , —NO , —CN , —R , —R , —SR , —OR , —NHR , —NRR , —S(O)NRR , —S(O)R , —C(O)R , —C(O)OR , —NRS(O)R , S(O)R , —S(O)NRR , —NRS(O)R , heterocyclyl , aryl , or heteroaryl.13. The compound of any one of - , wherein R is phenyl containing 1-5 heteroatoms selected from ...

Heterocyclyl Derivatives and their use as Prostaglandin D2 Receptor Modulators

The present invention relates to phenyl-substituted heterocyclyl derivatives of the formula (I), 2. The compound according to claim 1 , wherein{'sup': '1', 'Rrepresents hydrogen or halogen;'}{'sup': '2', 'Rrepresents hydrogen or halogen;'}{'sup': 3', '4', '5, 'sub': 1', '3', '1', '3, 'one of R, Rand Rrepresents carboxy-(C-C)alkyl or carboxy-(C-C)alkoxy and the other two represent hydrogen;'}{'sup': '6', 'Rrepresents hydrogen, methoxy or halogen;'}{'sup': '7', 'sub': 1', '4, 'Rrepresents hydrogen, (C-C)alkoxy, trifluoromethyl, trifluoromethoxy, halogen or methylsulfonyl;'}{'sup': '8', 'claim-text': [{'sub': 1', '4', '1', '2, '(C-C)alkyl which is mono-substituted with optionally substituted aryl, optionally substituted heteroaryl or optionally substituted aryl-(C-C)alkoxy; or'}, 'cyclopropyl which is mono-substituted with optionally substituted aryl;, 'Rrepresents'}n represents 1 or 2;m represents 1 or 2; andZ represents —NH—, —O— or a bond;or a salt thereof.3. The compound according to claim 1 , wherein{'sup': '1', 'Rrepresents fluoro;'}{'sup': 2', '3', '4', '6, 'R, R, Rand Rrepresent hydrogen;'}{'sup': '5', 'Rrepresents carboxy-methyl or 1-carboxy-ethyl;'}{'sup': '7', 'Rrepresents methoxy, ethoxy, isopropoxy or 2,2,2-trifluoroethoxy;'}{'sup': '8', 'claim-text': phenyl, wherein the phenyl is unsubstituted, mono-substituted with fluoro, chloro, methyl or methoxy, di-substituted with fluoro, or di-substituted with fluoro and chloro; or', 'pyridin-2-yl, wherein the pyridin-2-yl is unsubstituted, mono-substituted with methyl, or di-substituted with methyl and fluoro;, 'Rrepresents a methyl, ethyl or n-propyl group, which groups are independently mono-substituted with'}n represents 1;m represents 2; andZ represents —O— or a bond;or a salt thereof.4. The compound according to claim 1 , wherein{'sup': '1', 'Rrepresents fluoro, chloro or cyano;'}{'sup': 2', '3', '5', '6, 'R, R, Rand Rrepresent hydrogen;'}{'sup': '4', 'Rrepresents carboxy-methyl or 1-carboxy-ethyl;'}{'sup': ' ...