ИНГИБИТОРЫ ЦИТОЗОЛЬНОЙ ФОСФОЛИПАЗЫ A2

Изобретение относится к 3-{4-[(2-{5-хлор-1-(дифенилметил)-2-[2-({[2-(трифторметил)бензил]сульфонил}амино)этил]-1Н-индол-3-ил}этил)сульфонил]фенил}пропионовой кислоте или ее фармацевтически приемлемой соли, которое ингибирует цитозольную фосфолипазу А2 (цФЛА2), что позволяет использовать его при лечении астмы. 3 н.п. ф-лы, 2 табл., 5 ил.

ПРОИЗВОДНЫЕ ДИАРИЛОВОЙ КИСЛОТЫ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Изобретение относится к новым производным диариловой кислоты формулы (Ia) где представляет собой хинолинил или оксазолил, замещенный фенилом и необязательно замещенный галогеном, причем указанный фенил может быть замещен алкоксигруппой или галогеном; а = 1; b = 0 или 1; R1, R2, R3, R4 представляют собой водород; А представляет: R5, R6, R7, R8, R15, R16 представляют собой водород; с = 0; d = 0; g = целое число от 1 до 5; В и E представляют химическую связь; Z представляет собой HOOC-; R' и R" являются кольцевыми заместителями, более предпочтительно R' является водородом, алкокси, бензилокси, арилокси или фенилом; и R" является низшим алкилом или алкокси, и к их фармацевтически приемлемым солям. Изобретение также относится к фармацевтической композиции, обладающей активностью агониста или антагониста PPAR рецептора, на основе этих соединений. Технический результат - получение новых соединений формулы Ia и фармацевтической композиции на их основе в целях лечения заболеваний, которые можно ...

МОДУЛЯТОРЫ ЯДЕРНЫХ РЕЦЕПТОРОВ

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

НОВЫЕ ЛЕКАРСТВЕННЫЕ ВЕЩЕСТВА

Изобретение относится к органической химии и может найти применение в медицине. Описываются соединения или их соли, имеющие следующую общую формулу (I): где A=R-T1-, где R представляет собой радикал лекарственного вещества, такой как определено в формуле изобретения, T1=(CO), О, S, N или NR1c, где R1c представляет собой Н или C1-C5 алкил; В=-ТB -Х2-tBI, где ТB и tBI одинаковы или различны и выбраны из (СО), О, S, N или NR1c, где R1c такой, как определено выше, Х2 представляет собой бивалентную мостиковую группу, такую как соответствующий предшественник В, такой, как определено в формуле изобретения; С представляет собой бивалентный радикал -Tc-Y-, где Тс=(СО), О, S, N или NR1c, где R1c такой, как определено выше, Y имеет значения такие, как представлено в формуле изобретения. Также описывается фармацевтическая композиция на основе соединений формулы (I) для использования в случаях окислительного стресса и/или эндотелиальных дисфункций. Технический результат - получены новые соединения и ...

БЕНЗИЛАМИНОВЫЕ ПРОИЗВОДНЫЕ КАК ИНГИБИТОРЫ КАЛЛИКРЕИНА ПЛАЗМЫ

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

ПРОИЗВОДНЫЕ АМИНОМАСЛЯНОЙ, АМИНОПЕНТАНОВОЙ И АМИНОГЕКСАНОВОЙ КИСЛОТ

Изобретение относится к производным аминомасляной, аминопентановой и аминогексановой кислот общей формулы I где R1 - -COOR10; - (CH2)m-CONHOR10, -CONHNHR10, -(CH2)nSR50 или -Y-P (OR51)2; m = 0, 1, 2; n = 0-3; каждый из R2, R3, R4, R5, R6 и R7 независимо является водородом, С1-8 алкилом, С2-8 алкенилом, -OR11, -SR11, -NR12R13, Циклом 1, С1-8 алкилом, замещенным -OR11, -SR11, -NR12R13, -COR14, гуанидино или Циклом 1, или С2-8 алкенилом, замещенным -OR11, -SR11, -NR12R13, -COR14, гуанидино или Циклом 1, или R3 и R4, взятые вместе, представляют С1-8 алкилен, R5 и R6, взятые вместе, представляют С1-8 алкилен, R3 и R6, взятые вместе, представляют С1-8 алкилен, R2 и R3, взятые вместе, представляют С2-8 алкилен, R4 и R5, взятые вместе, представляют С2-8 алкилен или R6 и R7, взятые вместе, представляют С2-8 алкилен, или (1) R8 представляет собой 1) водород, 2) С1-8 алкил, 3) С1-8 алкоксикарбонил, 4) С1-8 алкил, замещенный -OR26, -SR26, -NR27R28 или -COR29, или 5) С1-8 алкоксикарбонил, замещенный ...

СОЕДИНЕНИЯ И КОМПОЗИЦИИ В КАЧЕСТВЕ МИМЕТИКОВ ТРО

... 1. Изобретение относится к новым соединениям формулы I ! ! где: n означает 0 или 1; Z означает N, CR8, где R8 означает Н, С1-С6алкил; R1, R2, R4 и R5 независимо означают Н, галоген, ОН, -XNR9R10, где X означает химическую связь, a R9 и R10 означают Н; R3 означает -NR11S(O)2R12, -NR11C(O)R12, -C(O)OR11, -NR11R12, S(O)2NR11R12 и -C(O)NR11R12, где R11 и R12 независимо означают H, С1-С6алкил; R6 означает галоген, С1-С6алкил; R7 означает фенил, замещенный 1 или 2 группами, независимо выбранными из фтора и С1-С6алкила, и его фармацевтически приемлемым солям. Соединения проявляют активность миметика ТРО, что позволяет получать из них лекарственные средства для повышения уровня тромбоцитов в крови животного. 4 н. и 4 з.п. ф-лы.

ГЕТЕРОЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ, ПРИМЕНИМЫЕ В КАЧЕСТВЕ АЛЛОСТЕРИЧЕСКИХ ЭФФЕКТОРОВ ПРИ МУСКАРИНОВЫХ РЕЦЕПТОРАХ

Описываются новые производные пиррола формулы (I), где Z - метиленовая группа, метиновая группа, группу формулы: >NH или группу формулы: = N -; W - метиленовая группа, метиновая группа и атом серы или группа формулы: >S -->(O)v, где v - 1 или 2, при условии, что Z не обозначает группу формулы: >NН, когда W - группа формулы: >S -->(O)v; каждая обозначает ординарную связь или двойную связь, при условии, что когда W обозначает атом серы или группа формулы: >S -->(O)v, связь между W и Z обозначает ординарную связь; по меньшей мере один из Y1 - Y4 обозначает группу формулы: -(А)p - B1 - T1, где А - атом кислорода, T1 - карбоксильная группа, защищенная карбоксильная группа, защищенная тиокарбоксигруппа, защищенная сульфонамидная группа или тетразолильная группа, B1 - алкиленовая группа, которая имеет 1-4 атома углерода, или алкиленовая группа, которая имеет 1-4 атома углерода и которая замещена, по меньшей мере, одним заместителем, выбранным из заместителей α, определенных ниже, и р = 0 или 1 ...

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 ПОЛУЧЕНИЯ МОНОНИТРАТА 1,4-БУТАНДИОЛА

... 1. Способ получения 4-нитрооксибутан-1-ола, включающий: ! стадию а) взаимодействие избытка 1,4-бутандиол с кислотой формулы R-C(O)OH, где R - линейная или разветвленная (С3-С5)-алкильная цепь, в присутствии кислого катализатора и в алифатическом неполярном растворителе, с последующим селективным отделением моноэфира 1,4-бутандиола формулы (I) ! ! где R как указано выше, от реакционной смеси; ! стадию b) нитрование RC(O)O-(CH2)4-ОН смесью концентрированной H2SO4 и концентрированной HNO3 или смесью азотной кислоты и уксусной кислоты или уксусного ангидрида с последующим выделением моноэфира 4-нитрооксибутан-1-ола формулы (II) ! ! где R как указано выше; ! стадию с) селективный гидролиз алкилкарбоксильного фрагмента соединения (II) неорганическим основанием в однослойной системе с последующей очисткой 4-нитрооксибутан-1-ола формулы (III) ! ! характеризующийся тем, что стадию нитрования осуществляют, используя моноэфир 1,4-бутандиола формулы (I), содержащий 1,4-бутандиол в количестве менее ...

СОЕДИНЕНИЯ, ЯВЛЯЮЩИЕСЯ АКТИВНЫМИ ПО ОТНОШЕНИЮ К РЕЦЕПТОРАМ, АКТИВИРУЕМЫМ ПРОЛИФЕРАТОРОМ ПЕРОКСИСОМ

... 1. Соединение, имеющее химическую структуру формулы I, а именно где U, V, W, Х и Y независимо представляют собой N или CR8, где в бициклической кольцевой структуре, показанной в формуле I, имеется не более чем 4 атома азота, и в любом из колец указанной бициклической кольцевой структуры имеется не более чем 2 атома азота; R1 представляет собой карбоксильную группу или ее эфир либо изостер карбоновой кислоты; R2 представляет собой атом водорода, возможно замещенный низший алкил, -CH2-CR12=CR13R14, -CH2-C≡CR15, возможно замещенный циклоалкил, возможно замещенный гетероциклоалкил, возможно замещенный арил, возможно замещенный аралкил, возможно замещенный гетероарил, возможно замещенный гетероаралкил, -C(Z)NR10R11, -C(Z)R20, -S(O)2NR10R11 или -S(O)2R21; R6 и R7 независимо представляют собой атом водорода, возможно замещенный низший алкил, возможно замещенный циклоалкил, возможно замещенный гетероциклоалкил, возможно замещенный арил, возможно замещенный аралкил, возможно замещенный гетероарил ...

КОМПОЗИЦИЯ КОРМА ДЛЯ ЖИВОТНЫХ

... 1. Композиция корма для животных, содержащая более 240 мкг свободной IAA (индолилуксусной кислоты) или ее производного на килограмм, в которой указанное производное выбирается из группы, состоящей из 4-гидрокси-IAA, 4-метокси-IAA, 5-гидрокси-IAA, 5-метокси-IAA, 6-гидрокси-IAA, 6-метокси-IAA, 7-гидрокси-IAA, 7-метокси-IAA и соединения, которое может превращаться в свободную IAA в 3, предпочтительно в 2 и более предпочтительно в 1 стадию. 2. Композиция корма по п.1, содержащая до 40 г свободной IAA или ее производного на килограмм. 3. Композиция корма по п.1, содержащая от 100 до 1000 мг свободной IAA или ее производного на килограмм. 4. Композиция корма по п.1, дополнительно содержащая фермент, способный превращать производное IAA в свободную IAA. 5. Композиция корма по п.4, содержащая ароматическое кольцо, в которой ароматическое кольцо в одном или более из 4, 5, 6 и 7 положений замещается метилом, амино, нитро, фторидом, хлоридом, бромидом или йодидом. 6. Композиция корма по любому из ...

ИНГИБИТОРЫ ВИРУСНОЙ РЕПЛИКАЦИИ, СПОСОБ ИХ ПОЛУЧЕНИЯ И ИХ ТЕРАПЕВТИЧЕСКОЕ ПРИМЕНЕНИЕ

... 1. Соединение формулы (I):где:- W представляет собой замещенный или незамещенный, частично или полностью ненасыщенный, ароматический или неароматический карбо- или гетероцикл;- а, b, с, d, е и f независимо представляют собой 0 или 1;- Qпредставляет собой CR, CR, CRR, N, NR, NR, S, О, С=O, C=S, N=O, SO, S(O);- Qпредставляет собой CR, NR;- Qпредставляет собой CCRRR, NCRRR;при условии, что Q-Qпредставляет собой N-C, C=C, N-N;- Qпредставляет собой CR, CR, CRR, N, NR, NR, S, O, C=O, C=S, N=O, S=O, S(O);- Qпредставляет собой CR, CR, CRR, N, NR, NR, S, O, C=O, C=S, N=O, S=O, S(O);- R, R, R, R, Rи Rнезависимо представляют собой водород, -CN, -ОН, -O-циклоалкил, -O-циклоалкенил, -O-циклоалкинил, -NH, -NR-циклоалкил, -NR-циклоалкенил, -NR-циклоалкинил, -S-циклоалкил, -S-циклоалкенил, -S-циклоалкинил, -СООН, -C(O)NH, -CF, -SONH, -NHSONH, -NHC(O)NH, -OC(O)NH, галоген, алкил, алкенил, алкинил, гетероалкил, гетероалкенил, гетероалкинил, арил, -O-арил, -NR-арил, -S-арил, арилалкил, арилалкенил, арилалкинил ...

МОДУЛЯТОРЫ ПЕРЕНОСЧИКОВ АТФ-СВЯЗЫВАЮЩИХ КАССЕТ

... 1. Соединение формулы II:IIили его фармацевтически приемлемая соль, где независимо для каждого случая:R представляет собой H, OH, OCH, или две R образуют вместе -CHCHCH-, -OCHO- или -OCFO-;Rпредставляет собой H или до двух C-Cалкилов;Rпредставляет собой H или F;Rпредставляет собой H или CN;Rпредставляет собой H, -CHCH(OH)CHOH, -CHCHN(CH)или -CHCHOH; иRпредставляет собой H, OH, -CHOCHCH(OH)CHOH, -CHOH, или Rи Rобразуют вместе конденсированное пирролидиновое кольцо.2. Соединение по п.1, где две R образуют вместе -OCFO-, Rпредставляет собой H, и Rпредставляет собой F.3. Соединение по п.1, где две R образуют вместе -OCFO-, Rпредставляет собой H, Rпредставляет собой F, и Rпредставляет собой H.4. Соединение по п.1, где две R образуют вместе -OCFO-, Rпредставляет собой H, Rпредставляет собой F, Rпредставляет собой H, и Rпредставляет собой -CHCH(OH)CHOH.5. Соединение по п.1, где две R образуют вместе -OCFO-, Rпредставляет собой H, Rпредставляет собой F, Rпредставляет собой H, и Rпредставляет собой ...

Новые антагонисты рецепторов интерлейкина-8

... 1. Производное индола, отличающееся тем, что оно выбрано из группы, включающей: i) соединения формулы в которой Х представляет собой двойную связь -С=С- или атом серы; r1 представляет собой галоген, нитрогруппу, трифторметильную группу или C1-С3 алкильную группу, r2, R3 и R4 представляют собой, независимо друг от друга, атом водорода, галоген, C1-С3 алкильную группу, нитрогруппу, трифторметильную группу или цианогруппу, либо r2 и r3 образуют совместно с ароматическим ядром, к которому они присоединены, конденсированный ароматический цикл; а n равно 2 или 3; и ii) сложные эфиры или соли, образованные с неорганическими или органическими основаниями, соединений формулы I. 2. Производное индола формулы I по п.1, в которой Х соответствует двойной связи -С=С-, отличающееся тем, что оно выбрано из группы, включающей: i) соединения формулы в которой r1 представляет собой галоген, нитрогруппу, трифторметильную группу или C1-С3 алкильную группу; R2, и r3 представляют собой, независимо друг от друга ...

Полиаминные аналоги в качестве цитотоксических агентов

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

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

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

ПЕРВИЧНЫЕ КАРБОКСАМИДЫ В КАЧЕСТВЕ ИНГИБИТОРОВ BIK

АМИДНЫЕ ПРОИЗВОДНЫЕ N-КАРБАМИД-ЗАМЕЩЕННЫХ АМИНОКИСЛОТ КАК МОДУЛЯТОРЫ ФОРМИЛПЕПТИДНОГО РЕЦЕПТОРА-1 (FPRL-1)

... 1. Соединение, представленное Формулой II, его энантиомеры, диастереоизомеры, таутомеры, гидраты, сольваты или фармацевтически приемлемые соли,,где:a равен 1, и b равен 0;a равен 0, и b равен 1;a равен 1, и b равен 1;Rпредставляет собой необязательно замещенный Cалкил, необязательно замещенный Cциклоалкил, необязательно замещенный гетероцикл, необязательно замещенный Cциклоалкил, необязательно замещенный Cарил, необязательно замещенный Cциклоалкенил, -NRRили OR;Rпредставляет собой необязательно замещенный Cалкил или необязательно замещенный Cарил;Rпредставляет собой водород, необязательно замещенный Cалкил, галоген, -COOR, -OR, NRR, NO, необязательно замещенный гетероцикл, необязательно замещенный Cциклоалкил, необязательно замещенный Cарил или необязательно замещенный Cциклоалкенил;Rпредставляет собой водород, необязательно замещенный Cалкил, галоген, -COOR, -OR, NRR, NO, необязательно замещенный гетероцикл, необязательно замещенный Cциклоалкил, необязательно замещенный Cарил или необязательно ...

Способ получения производных аминофенилкетона или их солей

Способ получения 3-[2-(диметиламино)-этил]-N-метил-1Н- индол-5-метансульфонамида или его солей, или сольватов

Изобретение касается гетероциклических веществ ,в частности, получения 3-[2-(диметиламино)-этил]-N-метил-1H- индол-5-метансульфонамида или его солей, или сольватов, обладающих сосудосуживающим действием, и может быть использовано в медицине. Цель изобретения - создание нового более активного и малотоксичного соединения указанного класса. Синтез ведут реакцией формальдегида с 3-[2-этиламино]-N-метил-1H-индол-5-метансульфонамидом и боргидридом или цианборгидридом натрия с последующим выделением целевого продукта или превращением его в необходимую соль или сольват. Новые вещества могут быть использованы для лечения боли, возникающей при расширении черепной сосудистой системы, без побочных действий. 1 табл.

VERBINDUNGEN ZUR BEHANDLUNG VON ERKRANKUNGEN,DIE MIT DES VASCULOGENESE UND/ODER ANGIOGENESE IN VERBUNDEN STEHEN.

NEUE INDOLDERIVATE, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL UND VERFAHREN ZU IHRER HERSTELLUNG

PHARMAZEUTISCHE VERBINDUNGEN

INDOL-, AZAINDOL- UND VERWANDTE HETEROZYKLISCHE AMIDOPIPERAZIN-DERIVATE

Indolyl-(3)-alkancarbonsaeure-niedrig-alkylester

"AKUTANZFARBSTOFFE UND DIESE ENTHALTENDE LICHTEMPFINDLICHE, THERMISCH ENTWICKELBARE ZUSAMMENSETZUNGEN UND MATERIALIEN"

Novel indole derivatives, process for their preparation and pharmaceutical preparations which contain these compounds

Indole derivatives of the general formula I in which R1 represents a hydrogen atom, an alkyl radical containing 1 to 6 carbon atoms or a benzyl radical and R2 represents a hydrogen atom, an alkyl radical containing up to 4 carbon atoms, a free or esterified hydroxyalkyl radical containing up to 4 carbon atoms or a free, amidated or esterified carboxyl group or carboxyalkyl group, and in which R3 denotes a hydrogen atom or an alkyl radical containing 1 to 6 carbon atoms, R4 denotes a hydrogen atom, or an alkyl radical containing 1 to 6 carbon atoms and R5 represents a hydrogen atom or an alkyl radical, alkenyl radical or cycloalkyl radical containing 1 to 6 carbon atoms which is optionally substituted by a free or esterified carboxyl group or by a phenyl radical which, if desired, is substituted, or a polymethylene group containing up to 8 carbon atoms and connecting two indole radicals of the general formula Ia in which R1, R2, R3 and R4 have the abovementioned meaning, ...

VERFAHREN ZUR HERSTELLUNG VON INDOLEN UND INDOLDERIVATEN, VERBUNDEN DURCH STELLUNG 4,5,6 ODER 7, VERBINDUNGEN UND ANWENDUNG.

NEUE BENZAMIDE ALS PPATY-MODULATOREN

Verfahren zur Herstellung von Indolyl-(3)-essigsaeureverbindungen

Verfahren zur Herstellung von neuen Alkan- und Aralkan-Carbonsaeure-Amidoximen

Verfahren zur Herstellung neuer heterocyclischer Verbindungen

Substituted indoles

The invention comprises compounds of the general formula: and salts and esters thereof wherein the dotted line in the 2(3)-position indicates that a single or double bond is present there, R1 and R3 are hydrogen atoms or C1-5-alkyl or C2-5 alkenyl groups, R2 is a hydrogen atom or a hydrocarbon or a substituted hydrocarbon group, R4 is a halogen atom or a hydrocarbon, hydroxy, nitro, amino substituted amino, mercapto, substituted mercapto, cyano, haloalkyl acyl, carboxy or derivatized carboxy group, R5 is hydrocarbonyl, R6 is a hydrogen atom or a hydrocarbonoxy group, a is 1, 2, 3 or 4 and b is 0, 1, 2 or 3 and the preparation thereof by reacting together, in an alkaline medium either (a) an appropriate benzyl ester of a strong acid or (b) an appropriate benzyl alcohol and an ester of a strong acid, with a compound of the formula: wherein Y is a hydrogen atom or a hydrocarbon group or (where the 2(3) linkage is saturated) by hydrogenating the corresponding ...

Water-soluble fluoro-substituted cyanine dyes as reactive fluorescence labelling reagents

Combinatorial synthesis on soluble polyvalent supports

(3-indolyl)-aliphatic acids and esters and amides thereof

Novel compounds of the general formula (wherein R1 is an aromatic radical of one ring or two fused rings in which any hetero atoms are nitrogen, sulphur or oxygen and in which any substituent is a halogen atom or a C1- 5 alkyl, C1- 5 alkylthio, C1- 5 alkoxy, CF3, phenoxy, (C1- 5 alkyl) phenoxy, (C1- 5 alkoxy) phenoxy, halophenoxy, CF3CO, CHF2CO, CH2FCO, di-(C1- 5 alkyl) sulphamoyl, C1- 5 alkanoyl, di-(C1- 5 alkyl) carbamoyl, CN, C2- 6 carbalkoxy, CHO, CF3S, C1- 5 alkylsulphinyl, C1- 5 alkylsulphonyl, benzylthio, (C1- 5 alkyl) benzylthio, (C1- 5 alkoxy) benzylthio, halobenzylthio, SH, NO2, NH2, C1- 5 alkylamino, di-(C1- 5 alkyl) amino, C1- 5 alkanoylamino, OH, C1- 5 alkanoyloxy, CF3COO, CHF2COO, CH2FCOO, benzyloxy, (C1- 5 alkyl) benzyloxy, (C1- 5 alkoxy) benzyloxy, phenyl, C2- 5 alkenyloxy or halobenzyloxy group, R2 is H or a C2- 5 alkenyl or C1- 5 alkyl radical, R3 is H or a C1- 5 alkyl or C2- 5 alkenyl radical and R13 is H, or R3 and R13 jointly form an alkylidene radical ...

HETEROCYCLIC COMPOUNDS

HETEROCYCLIC COMPOUNDS

AN INDOLE DERIVATIVE

A compound of formula (I> and its physiologically acceptable salts and solvates are described as useful in treating and/or preventing pain resulting from dilation of the cranial vasculature, in particular migraine. The compound (I) may be prepared, for example, by cyclising a compound of formula (II> ...

Fluoro-substituted 2-methyl-indolinium precursors of reactive fluorescence-labelling water-soluble cyanine dyes

There are disclosed fluoro-substituted 2-methyl-indolinium compounds of formula (A) (for use as precursors of reactive water-soluble fluoro-substituted cyanine dyes that are useful for fluorescence-labelling and detection of biological and other materials, especially biological target molecules): wherein: either (I)

R<1>

and R<11> are -L-M -L-P or -(CH2)k-SO3H provided that at least one of R<1> and R<11> is -L-M or -L-P;

R<12>

is C1-6 alkyl;

R<3-6>

are -H -SO3H -SO2-CF3 or -(CF2)m-F or R<3> and R<4>, or R<5> and R<6>, together form a fused carbo-aromatic 6-membered ring which is optionally substituted by -SO3H, -SO2-CF3 or -(CF2)m-F;

L

is a linking group:

M

is a target bonding group (such as a reactive group, a functional group for reacting with a reactive group, or an affinity tag);

P

is a conjugated component;

k

is 1-10;

m

is 0-4; provided that (i) at least one of groups ...

Подробнее

Compounds

Compounds of general formula (I): wherein R1, R2, R3, R4, R5a, R5b X1, X2, Z and Y are as defined herein are positive modulators of the calcium-activated chloride channel (CaCC), TMEM16A. The compounds are useful for treating diseases and conditions affected by modulation of TMEM16A, particularly respiratory diseases and conditions.

Indoles

... 1,136,489. Indoles. MERCK & CO. Inc. 4 Oct., 1966 [7 Oct., 1965], No. 44313/66. Heading C2C. Novel diesters of the general formula wherein A is a hydrogen atom or a substituted or unsubstituted carbocyclic or heterocyclic acyl radical preferably an aromatic carbocyclic or heterocyclic acyl radical containing less than three fused rings; R 1 is a hydrogen atom or C 1-5 alkyl, C 1-5 alkoxy, haloalkyl, hydroxyl, mercapto, benzylmercapto, benzyloxy, C 3-6 cyclo-alkyl, C 3-6 cyclo-alkoxy, di-(C 1-5 alkyl)- amino, bis-(C 1-5 hydroxyalkyl)-amino, pyrrolidino, morpholino, piperazino or C 2-5 alkenyl group; R 2 is a hydrogen atom or C 1-5 alkyl or C 1-5 alkoxy radical and R 3 is a bulky labile group subject to non-aqueous cleavage, e.g. t-butyl, are prepared by the interaction of the appropriate aniline, having not more than one substituent ortho to the nitrogen atom thereof and being free of deactivating, meta-directing, electron-attracting substituents, and a diester of -halo-#-keto adipic acid ...

INDOLE DERIVATIVES

... 1382917 1-Acylindolines AMERICAN CYANAMID CO 3 May 1972 [27 May 1971] 56237/73 Divided out of 1382916 Heading C2C The invention comprises compounds of formula where R 1 is H, Cl, Br, C 1-4 alkoxy, NO 2 , NH 2 , AcNH or NMe 2 , and R 2 is H, C 1-4 alkoxy or NO 2 , or R 1 R 2 is -OCH 2 O-; R 3 is H or Me; Y is PhCO (possibly substituted by Cl or NO 2 ) or C 2-4 alkanoyl; and Z is OH, Cl, Br, MeSO 3 or p-TsO. In examples, these compounds are prepared by (a) acylating the corresponding N- unsubstituted compounds (and if necessary saponifying an initial compound where Z = (e.g.) OAc); (b) introducing an NO 2 group by nitration and if appropriate reducing to NH 2 ; (c) converting Z = OH to the other values for Z; (d) (for Z = OH) reducing a corresponding indoline-3-acetic acid or its ester, or its mixed anhydride with EEOCO 2 H. Intermediates otherwise prepared have the formulae RH, 3-R:C(OH)CO 2 Et, 3-RCH 2 CO 2 Et, [R being a 2-oxoindoline residue, substituted by 5,6-(MeO) 2 or 5,6-(OCH 2 O ...

INDOLYLALKYLPIPERIDINES PROCESS FOR THEIR MANUFACTURE AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM

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

5-Phenyl-pentanoic acid derivatives as matrix metalloproteinase inhibitors for the treatment of asthma and other disease

Indole derivatives useful in therapy.

Compounds of formula I, and their pharrnaceutically acceptable derivatives. Rs wherein R1 and R2 are optional substiruents and independently represent C1-6 alkyj, C,^ alkenyl [optionally substituted by CO:H or Co2(C1-6 alkyl)], C,.6 alkynyl, halogen, C,.; perfluoroalkyl, (CH2)raAr', (CHJ^Het1, (CH,)mCONR7R3, (CH3)mC02R3, O(CH,)qCO,R3, CCH,)mCOR3, (CH,)mOR3, 0(CH!)pORi, (CH,)mNR7R3, CO,(CH:),NR7R3, (CH,)mCN, S(0)nR.3, SO;NR7RS, CONfHfCH^-Ar1 or CONH(CHJmHet'; R3 represents H, C^ alk>'l, (CKJjNR'R10, SO2R10, SO,NR9R10, (CHJ^COR10, C,^ alkenyt, C,.5 aUcynyl, (CHJ^CONR^R10, (CH,)raCO,R10, (CH,JPCN, (CH,),Rio or (CH,)POR10; R4 represents H or C,^ alkyl: R3 represents H or OK; R° represents phenyl optionally iHised to a heterocyclic rins, the group as a whole beina optionally substituted; R"'° are fully defined here:.-, and may independently represent Ar: or Het:; Z represents CO:K, CONK(;ecazol-5-yl), CONHSO:0(CM alkyl), CO:.V, CO;(C,.., alkyl). :etrazol-5-yl, CONKSO:.Ar;. CONHSO,(CH,)rV or ...

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

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

Indole derivatives useful in the treatment of osteoporosis.

A compound of formula (i)or a salt thereof, or a solvate thereof, wherein either (i)ra represents a group r5 which is hydrogen alkyl or optionally substituted aryl and rb represents a moiety of formula (a), wherein x represents a hydroxy or an alkoxy group wherein the alkyl group may be substituted or unsubstituted or x represents a group nrsrt wherein rs and rt each independently represent hydrogen, alkyl, substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted arylalkyl, an optionally substituted heterocyclic group or an optionally substituted heterocyclylalkyl group, or rs and rt together may form a heterocyclic group; re represents an alkyl or a substituted or unsubsituted aryl group; and r2, r3 and r4 each independently represent hydrogen, alkyl, aryl or sustituted aryl or (ii)ra represents a moiety of the above defined formula (a)and rb represents the above defined r5; r6 and r7 each independently represents hydrogen, hydroxy, amino, ...

COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS

Indazole Compounds And Pharmaceutical Compositions For Inhibiting Protein Kinases, And Methods For Their Use.

Indazole compounds that modulate and/or inhibit the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

5-phenyl-pentanoic acid derivatives as matrix metalloproteinase inhibitors for the treatment of asthma and other disease.

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

Indole derivatives useful in therapy

Indole derivatives useful in the treatment of osteoporosis

Indazole compounds and pharmaceutical compositions for inhibiting protein kinases and methods for their use

N-(3-amino-2-hydroxy-propyl) substituted alkylamide compounds.

Disclosed are compounds of the formula (I): useful in treating Alzheimer' s disease and other similar diseases. These compounds include inhibitors of the betasecretase enzyme that are useful in the treatment of Alzeheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical composition and methods of treatment to reduce A beta peptide formation.

5-Phenyl-pentanoic acid derivatives as matrix metalloproteinase inhibitors for the treatment of asthma and other disease

Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use

The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2(cox-2)inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2(cox-2)inhibitor, and optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous sythesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or optionally,at least ne therauptic agent, such as steroids, nonsteroidal antiinflamatory compounds (nsaid),5-lipoxygenase (5-lo)inhibitors, leukotriene b4 (ltb4)receptor antagonists, leukotriene a4 (lta4)hydrolase inhibitors, 5-ht agonists, 3 hydroxy-3-methylglutaryl coenzyme a (hmg-c0a)inhibitors,h2 antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating or non-sedating anti-histamines, inducible nitric oxide sythase inhibitors, opioids, analsgesic, helicopter pylori inhibitors ...

5-Phenyl-pentanoic acid derivatives as matrix metalloproteinase inhibitors for the treatment of asthma and other disease

New derivatives of indol, their method of preparation, their application to the fight against the parasites and the compositions containing them.

2,3-Substituted indole compounds as COX-2inhibitors.

N-(3-amino-2-hydroxy-propyl)substituted alkylamidecompounds.

Substitued trans-1,2-diaminocyclohexyl amide compounds.

Synthesis of N-aroyl-3-indolyl-aliphatic compounds.

Indole derivatives useful as endothelin receptor antagonists

Indole derivatives useful in the treatment of osteoporosis

Indazole compounds and pharmaceutical compositionsfor inhibiting protein kinases, and methods for t heir use.

Indazole compounds and pharmaceutical compositions for inhibiting protein kinases and methods for their use

COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS

Indazole compounds and pharmaceutical compositions for inhibiting protein kinases and methods for their use

Indole derivatives useful in therapy

N-(3-amino-2-hydroxy-propyl) substituted alkylamide compounds.

Indole derivatives useful in the treatment of osteoporosis

COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS

N-(3-amino-2-hydroxy-propyl) substituted alkylamide compounds.

Nitrosated and nitrosylated cyclooxygenase-2 inhibitors compositions and methods of use

PROCEDURE FOR THE PRODUCTION OF NEW INDOLDERIVATEN AND YOUR SALTS

PROCEDURE FOR THE PRODUCTION OF NEW DIHYDROPYRIDINCARBONSAEUREAMIDEN AND - ESTERS

Process for the preparation of novel amides and esters of 1,4-dihydropyridine-3,5-dicarboxylic acids of the formula XXI in which R<2> and R<6> are a lower alkyl, hydroxyalkyl, alkoxyalkyl, alkylaminoalkyl or dialkylaminoalkyl group, R<4> is cycloalkyl, bicycloalkenyl, heteroaryl or optionally substituted aryl, R<5> has the meaning of R<2> or XXII, X is O or NH, Y is an alkylene, alkyleneoxyalkylene, alkylenethioalkylene or alkyleneaminoalkylene chain and Z is optionally substituted phenyl, pyridinyl or pyrimidinyl. Compounds of this type show an effect as calcium and alpha-adrenergic blockers on in vitro investigation and, on in vivo testing, have an antihypertensive, antiischaemic effect and an effect inhibiting platelet function. ...

PROCEDURE FOR THE PRODUCTION OF INHIBITORS THE HMG COA REDUKTASE ONES

VERFAHREN ZUR HERSTELLUNG VON 3-INDOLYLMILCHSAURE

DIPEPTIDE NITRILES

2-PHENYLINDOLE AS ANTAGONISTS of the PROSTAGLANDIN-D2-REZEPTORS

CARBAMINSÄUREDERIVATE CONTAINING AN AMIDE GROUP FOR THE TREATMENT OF MALARIA

NEW BENZAMIDE AS PPATY MODULATORS

BICYCLI CONNECTIONS

AS CETP HEMMER SUITABLE HOMOUND HETERO-CYCLIC CONNECTIONS

PROCEDURE FOR THE PRODUCTION OF NEW DIHYDROPYRIDINCARBONSAEUREAMIDEN AND - ESTERS

PROCEDURE FOR THE PRODUCTION OF DIHYDROPYRIDYLIMIDATESTERN

PROCEDURE FOR THE PRODUCTION OF A NEW INDOLDERIVATES AND ITS SALTS

PROCEDURE FOR THE PRODUCTION NEW INDOLE AND YOUR SALTS

PROCEDURE FOR THE PRODUCTION OF INDOLYLLACETONEN

INDOLDERIVATE

PROCEDURE FOR THE PRODUCTION OF NEW INDOLDERIVATE AND YOUR SALTS

PHARMACEUTICAL CONNECTIONS

PROCEDURE FOR THE PRODUCTION OF PROTECTED AMIDINE

PROCEDURE FOR THE PRODUCTION OF NEW INDOLDERIVATE AND YOUR SALTS

Methods of treating emesis using growth hormone secretagogues

The present invention relates to methods of treating or preventing emesis and improving a subject's ASAS score by administering to the subject an effective amount of a growth hormone secretagogue compound or a pharmaceutically acceptable salt, hydrate or solvate thereof.

Chemoselective enrichment for compound isolation

Chemoselective isolation of hydroxyl group-containing and carboxyl group-containing compounds is accomplished via formation of polymeric silyl ethers and polymeric siloxyl esters, respectively. Preparation of chemoselective polymeric reagents for capture of hydroxyl group containing compounds and carboxyl group containing compounds is described.

PROCESS FOR THE PREPARATION OF HMG-COA REDUCTASE INHIBITORS AND INTERMEDIATES THEREOF

The present invention provides an improved process for preparing HMG-CoA reductase inhibitors such as rosuvastatin calcium, fluvastatin sodium, and pitavastatin calcium under a mild condition, using a novel amide-bond-containing compound having R—N—O—Rmoiety as a key intermediate. And also, the present invention provides the novel compound, an intermediate useful for the preparation thereof, and a process for the preparation thereof. 3. The process of claim 2 , wherein the acid is selected from the group consisting of hydrochloric acid claim 2 , sulfuric acid claim 2 , phosphoric acid claim 2 , nitric acid claim 2 , acetic acid claim 2 , formic acid claim 2 , sulfonic acid claim 2 , and a mixture thereof.5. The process of claim 4 , wherein the hydrolyzing is performed by reacting the compound of Formula 6 with an alkali metal hydroxide or an alkaline earth metal hydroxide.6. The process of claim 4 , wherein the acid is selected from the group consisting of hydrochloric acid claim 4 , sulfuric acid claim 4 , phosphoric acid claim 4 , nitric acid claim 4 , acetic acid claim 4 , formic acid claim 4 , sulfonic acid claim 4 , and a mixture thereof.7. The process of claim 1 , wherein Rand Rare independently methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , or phenyl.16. The process of claim 15 , wherein the reacting is performed in the presence of a base selected from the group consisting of sodium C˜Calkoxide claim 15 , potassium C˜Calkoxide claim 15 , sodium carbonate claim 15 , potassium carbonate claim 15 , lithium carbonate claim 15 , cesium carbonate claim 15 , sodium bicarbonate claim 15 , potassium bicarbonate claim 15 , potassium phosphate claim 15 , 1 claim 15 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU) claim 15 , 1 claim 15 ,4-diazabicyclo[2.2.2]octane (DABCO) claim 15 , 1 claim 15 ,5-diazabicyclo[4.3.0]non-5-ene (DBN) claim 15 , pyridine claim 15 , dimethylaminopyridine claim 15 , triethylamine claim 15 , lithium bis(trimethylsilyl)amide ...

NOVEL COMPOSITIONS AND METHODS FOR TREATING CANCER

Provided herein are methods and compositions inter alia for treating diseases, including hyperproliferative diseases, migraine headaches, and depression. 7. The compound of claim 1 , wherein{'sup': 1A', '7A', '7A, 'Ris independently —C(O)Ror —C(O)—OR;'}{'sup': 1B', '7B', '7B, 'Ris independently —C(O)Ror —C(O)—OR;'}{'sup': '7A', 'sub': 1', '20', '3', '8', '6', '10, 'Ris independently hydrogen, substituted or unsubstituted C-Calkyl, substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C-Ccycloalkyl, substituted or unsubstituted 3 to 8 membered heterocycloalkyl, substituted or unsubstituted C-Caryl, or substituted or unsubstituted 5 to 10 membered heteroaryl; and'}{'sup': '7B', 'sub': 1', '20', '3', '8', '6', '10, 'Ris independently hydrogen, substituted or unsubstituted C-Calkyl, substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C-Ccycloalkyl, substituted or unsubstituted 3 to 8 membered heterocycloalkyl, substituted or unsubstituted C-Caryl, or substituted or unsubstituted 5 to 10 membered heteroaryl.'}8. The compound of claim 1 , wherein{'sup': 2A', '9A', '9A, 'Ris independently —C(O)Ror —C(O)—OR;'}{'sup': 2B', '9B', '9B, 'Ris independently —C(O)Ror —C(O)—OR;'}{'sup': '9A', 'sub': 1', '20', '3', '8', '6', '10, 'Ris independently hydrogen, substituted or unsubstituted C-Calkyl, substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C-Ccycloalkyl, substituted or unsubstituted 3 to 8 membered heterocycloalkyl, substituted or unsubstituted C-Caryl, or substituted or unsubstituted 5 to 10 membered heteroaryl; and'}{'sup': '9B', 'sub': 1', '20', '3', '8', '6', '10, 'Ris independently hydrogen, substituted or unsubstituted C-Calkyl, substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C-Ccycloalkyl, substituted or unsubstituted 3 to 8 membered heterocycloalkyl, substituted or unsubstituted C-Caryl, or substituted or unsubstituted 5 to ...

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.

Cyanine compounds

Compounds used as labels with properties comparable to known fluorescent compounds. The compounds can be conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

PEPTIDOMIMETIC COMPOUNDS AS IMMUNOMODULATORS

The present invention relates to novel peptidomimetic compounds as therapeutic agents capable of inhibiting the programmed cell death 1 (PD1) signalling pathway. The invention also relates to derivatives of the therapeutic agents. The invention also encompasses the use of the said therapeutic agents and derivatives for treatment of disorders via immunopotentiation comprising inhibition of immunosuppressive signal induced due to PD-1, PD-L1, or PD-L2 and therapies using them. 2. The compound according to claim 1 , wherein Ris —OH claim 1 , —OCHor —OCOCH.3. The compound according to claim 1 , wherein R′ claim 1 , Rand R′ are hydrogen.4. The compound according to claim 1 , wherein Ris —C(═O)—Am—R; wherein Amis selected from Ser claim 1 , Thr claim 1 , Asp claim 1 , Trp claim 1 , Ile or Phe; and Ris same as defined in .5. The compound according to claim 1 , wherein amino acids of Amis either D or L-amino acids.12. A pharmaceutical composition comprising at least one compound according to and/or a pharmaceutically acceptable salt or a stereoisomer thereof claims 1 , and a pharmaceutically acceptable carrier or excipient.13. The pharmaceutical composition of further comprising at least one additional pharmaceutical agent wherein the said additional pharmaceutical agent is an anticancer agent claim 12 , chemotherapy agent claim 12 , or antiproliferative compound.14. A compound according to claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof claim 1 , for use as a medicament.15. A compound according to or a pharmaceutically acceptable salt or a stereoisomer thereof claim 1 , for use as a medicament for the treatment of cancer or infectious disease.16. A method of modulating an immune response mediated by PD-1 signaling pathway in a subject claim 1 , comprising administering to the subject therapeutically effective amount of compound according to such that the immune response in the subject is modulated.17. A method of inhibiting growth of tumour cells ...

NOVEL COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES

This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds. The compounds have the formula (A1), wherein R, R, R, R, R, E, n, Y, Y, Y, Y, Y, B, R, and m are as defined in the claims. 5. The compound of claim 1 , wherein B is aryl and Ris selected from hydrogen claim 1 , halogen claim 1 , —OH claim 1 , cyano claim 1 , Calkyl claim 1 , Calkoxy claim 1 , Calkoxycarbonyl claim 1 , trifluoromethyl; trifluoromethoxy.6. The compound of claim 1 , wherein each of R claim 1 , R claim 1 , R claim 1 , Rand Rare hydrogen.9. A pharmaceutical composition comprising one or more pharmaceutically acceptable excipients and a therapeutically effective amount of the compound of .10. (canceled)11. A method of preventing or treating a neurodegenerative disorder in a subject claim 1 , the method comprising:{'claim-ref': [{'@idref': 'CLM-00001', 'claim 1'}, {'@idref': 'CLM-00009', 'claim 9'}], 'administering to a subject in need thereof a compound of or a pharmaceutical composition of .'}12. The method according to claim 11 , wherein the neurodegenerative disorder is selected from Alzheimer's disease claim 11 , Pick's disease claim 11 , corticobasal degeneration claim 11 , progressive supranuclear palsy claim 11 , frontotemporal dementia claim 11 , parkinsonism claim 11 , parkinsonism linked to chromosome 17 claim 11 , FTDP-17 claim 11 , Parkinson's disease claim 11 , diffuse Lewy body disease claim ...

Aryl Substituted Indoles and Their Use as Blockers of Sodium Channels

The invention relates to aryl and heteroaryl substituted compounds of Formula (I), and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein G, R, and Z-Zare defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain. 2. The compound of claim 1 , wherein Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.3. The compound of claim 1 , wherein Zis CR claim 1 , Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.4. The compound of claim 1 , wherein Zis CR claim 1 , Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.5. The compound of claim 1 , wherein Zis CR claim 1 , Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.6. The compound of claim 1 , wherein Zis CR claim 1 , Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.7. The compound of claim 1 , wherein Zis CR claim 1 , Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.8. The compound of with the proviso that when Zis N claim 1 , Z claim 1 , Z claim 1 , Z claim 1 , and Zare CR claim 1 , CR claim 1 , CR claim 1 , and CR claim 1 , respectively claim 1 , G is G claim 1 , wherein r is 0 claim 1 , and Ais optionally substituted heteroaryl claim 1 , then Ris not A.10. The compound of with the proviso that when Z claim 1 , Z claim 1 , Z claim 1 , Z claim 1 , and Zare CR claim 1 , CR claim 1 , CR claim 1 , CR claim 1 , and CR claim 1 , respectively claim 1 , R claim 1 , R claim 1 , and Rare hydrogen claim 1 , Ris A claim 1 , G is G claim 1 , wherein Rand Rare H and Ris haloalkylcarbonyl or optionally substituted arylcarbonyl claim 1 , then Ris other than alkoxycarbonyl.23. The compound of claim 1 , wherein G is G.24. ...

Modulators of atp-binding cassette transporters

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

CYANINE COMPOUNDS

Compounds used as labels with properties comparable to known fluorescent compounds. The compounds can be conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided. 5. A method of labeling at least one biomolecule claim 2 , the method comprising providing a composition comprising at least one excipient and the compound of in an effective concentration to at least one biomolecule under conditions sufficient for labeling the biomolecule with the compound.6. The method of wherein the biomolecule is selected from the group consisting of a protein claim 5 , antibody claim 5 , enzyme claim 5 , nucleoside triphosphate claim 5 , oligonucleotide claim 5 , biotin claim 5 , hapten claim 5 , cofactor claim 5 , lectin claim 5 , antibody binding protein claim 5 , carotenoid claim 5 , carbohydrate claim 5 , hormone claim 5 , neurotransmitter claim 5 , growth factors claim 5 , toxin claim 5 , biological cell claim 5 , lipid claim 5 , receptor binding drug claim 5 , fluorescent proteins claim 5 , organic polymer carrier material claim 5 , inorganic carrier material claim 5 , and combinations thereof.7. A method of labeling at least one biomolecule claim 3 , the method comprising providing a composition comprising at least one excipient and the compound of in an effective concentration to at least one biomolecule under conditions sufficient for labeling the biomolecule with the compound.8. The method of wherein the biomolecule is selected from the group consisting of a protein claim 7 , antibody claim 7 , enzyme claim 7 , nucleoside triphosphate claim 7 , oligonucleotide claim 7 , biotin claim 7 , hapten claim 7 , cofactor claim 7 , lectin claim 7 , antibody binding protein claim 7 , carotenoid claim 7 , carbohydrate claim 7 , hormone claim 7 , neurotransmitter claim 7 , growth factors claim 7 , toxin claim 7 , biological cell claim 7 , ...

MODIFIED CARBOCYANINE DYES AND THEIR CONJUGATES

Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens. 117.-. (canceled)19. The compound of claim 18 , wherein Y represents the atoms necessary to form two fused aromatic rings.20. The compound of claim 18 , wherein the atoms of Y are selected from —CH and —C.21. The compound of claim 18 , wherein X is —CRR.22. The compound of claim 21 , wherein Ris C-Calkyl.23225. The compound of claim claim 21 , wherein Ris methyl.24. The compound of claim 18 , wherein α is 1.25. The compound of claim 18 , wherein Ris C-Calkyl.26. The compound of claim 25 , wherein Ris methyl or ethyl.27. The compound of claim 18 , wherein W represents the atoms necessary to form two fused aromatic rings.28. The compound of claim 18 , wherein the atoms of W are selected from —CH and —C.29. The compound of claim 18 , wherein Z is —CRR.30. The compound of claim 29 , wherein each of Rand Ris methyl.31. The compound of claim 18 , wherein δ is 1.32. The compound of claim 18 , wherein Ris methyl or ethyl.33. The compound of claim 18 , wherein a is 1 and b is 0.34. The compound of claim 18 , wherein Ris a phosphoramidite.38. The compound of claim 18 , wherein L comprises ether bonds.39. The compound of claim 18 , wherein L contains 4-10 nonhydrogen atoms claim 18 , including one or two heteroatoms.40. The compound of claim 18 , wherein L contains 1-6 carbon atoms. This application is a continuation of U.S. Ser. No. 13/556,643, filed Jul. 24, 2012, which is a continuation of U.S. Ser. No. 12/906,304, filed Oct. 18, 2010 (now U.S. Pat. No. 8,252,932), which is a continuation of U.S. Ser. No. 11/675,030, ...

COMPOUND FOR MODULATING DDAH AND ADMA LEVELS, AS WELL AS METHODS OF USING THEREOF TO TREAT DISEASE

Disclosed are compounds that can modulate DDAH and the amount of asymmetric dimethylarginine (ADMA) in a subject. Also provided are pharmaceutical compositions comprising these compounds, as well as methods of using these compositions to treat and/or prevent diseases associated with elevated or low levels of DDAH and ADMA. 2. The method of claim 1 , wherein Y is a substituted or unsubstituted aryl ring claim 1 , optionally wherein Y is selected from an oxazole ring claim 1 , a pyridinyl ring claim 1 , a thiazole ring claim 1 , and a thiophene ring.5. The method of claim 4 , wherein Xand Xarei) both CH;{'sub': '2', 'ii) independently O or CHor'}iii) together with the bond to which they are attached form a 3-membered carbocyclic ring.7. The method of claim 1 , wherein Xand Xtogether with the bond to which they are attached forms a 3-membered carbocyclic ring.8. (canceled)9. The method of wherein said composition is administered for treating or preventing a disease or condition associated with elevated levels of asymmetric dimethylarginine (ADMA) in a subject.10. The method of claim 9 , wherein the risk factors claim 9 , disease or condition includes hypertension claim 9 , heart failure claim 9 , pulmonary arterial hypertension claim 9 , erectile dysfunction claim 9 , coronary and peripheral arterial disease claim 9 , renal disease claim 9 , insulin resistance claim 9 , diabetes claim 9 , atrial fibrillation claim 9 , sickle cell disease claim 9 , organ damage claim 9 , sepsis claim 9 , renal failure claim 9 , endothelial dysfunction claim 9 , vascular disease claim 9 , or a combination thereof.11. The method of wherein said composition is administered for reducing fibrosis in a cell or tissue.1213-. (canceled)14. The method of claim 11 , wherein the fibrosis is associated with a fibrotic condition of the lung claim 11 , a fibrotic condition of the liver claim 11 , a fibrotic condition of the heart or vasculature claim 11 , a fibrotic condition of the kidney claim 11 , ...

INHIBITORS OF HISTONE LYSINE SPECIFIC DEMETHYLASE (LSD1) AND HISTONE DEACETYLASES (HDACS)

A series of phenelzine analogs comprising a phenelzine scaffold linked to an aromatic moiety and their use as inhibitors of lysine-specific demethylase 1 (LSD1) and/or one or more histone deacetylases (HDACs) is provided. The presently disclosed phenelzine analogs exhibit potency and selectivity for LSD1 versus MAO and LSD2 enzymes and exhibit bulk, as well as, gene specific histone methylation changes, anti-proliferative activity in several cancer cell lines, and neuroprotection in response to oxidative stress. Accordingly, the presently disclosed phenelzine analogs can be used to treat diseases, conditions, or disorders related to LSD1 and/or HDACs, including, but not limited to, cancers and neurodegenerative diseases. 16-. (canceled)89-. (canceled)11. (canceled)13. A pharmaceutical composition comprising a compound of Formula (IIb).14. The pharmaceutical composition of claim 13 , further comprising one or more additional therapeutic agents.15. The pharmaceutical composition of claim 14 , wherein the one or more additional therapeutic agents is selected from the group consisting of a histone deacetylase (HDAC) inhibitor claim 14 , a DNA methyltransferase (DNMT) inhibitor claim 14 , and combinations thereof.16. A method for inhibiting lysine-specific demethylase 1 (LSD1) and/or one or more histone deacetylases (HDACs) claim 14 , the method comprising administering to a subject a compound of Formula (IIb) claim 14 , or a pharmaceutically acceptable salt thereof claim 14 , in an amount effective to inhibit LSD1 or one or more HDACs.18. The method of claim 17 , wherein the disease claim 17 , disorder claim 17 , or condition associated with LSD1 and/or one or more histone deacetylases (HDACs) is a cancer.19. The method of claim 17 , wherein the treating of the disease claim 17 , disorder claim 17 , or condition associated with LSD1 and/or one or more histone deacetylases (HDACs) includes activating one or more tumor suppressors silenced in cancer by an epigenetic ...

NOVEL COMPOUNDS AND COMPOSITIONS FOR INHIBITION OF FASN

The present invention relates to compounds and composition for inhibition of FASN, their synthesis, applications, and antidotes. An illustrative compound of the invention is shown below: 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a C-Chydroxyl-alkyl either unsubstituted or substituted with —CHor CHF.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a 5-membered cycloalkyl either unsubstituted or substituted with substituents selected from the group consisting of —R claim 1 , —OR claim 1 , —NHRand —NRR1.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a 3 membered cycloalkyl wherein said 3 membered cycloalkyl is either unsubstituted or optionally substituted with substituents selected from the group consisting of deuterium claim 1 , —R claim 1 , —OR claim 1 , —NHR claim 1 , and —NRR.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a 4 membered cycloalkyl wherein said 3 membered cycloalkyl is either unsubstituted or optionally substituted with substituents selected from the group consisting of deuterium claim 1 , —R claim 1 , —OR claim 1 , —NHR claim 1 , and —NRR.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a substituted or unsubstituted 9-membered 6 claim 1 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 heteroatoms and said heteroatoms are independently O claim 1 , S claim 1 , or N.7. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris a substituted or unsubstituted 9-membered 6 claim 2 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 2 , 2 claim 2 , 3 claim 2 , or 4 heteroatoms and said heteroatoms are independently O claim 2 , S claim 2 , or N.8. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , ...

METHODS AND COMPOSITIONS FOR TREATING AMYLOID-RELATED DISEASES

Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease. 1232-. (canceled)234. The compound of claim 233 , wherein Ris hydrogen.235. The compound of claim 233 , wherein Ris straight chain alkyl.236. The compound of claim 233 , wherein Ris t-butyl.237. The compound of claim 233 , wherein Ris carbocyclic.238. The compound of claim 233 , wherein Ris C-Cbicycloalkyl.239. The compound of claim 233 , wherein said bicyclic fused ring group is indolyl.240. The compound of claim 233 , wherein Lis CHCHor absent.251. A method of treating or preventing an amyloid-related disease in a subject comprising administering to a subject in need thereof a compound of in an amount effective to treat or prevent an amyloid related disease.252. The method according to claim 251 , wherein said amyloid-related disease is Alzheimer's disease claim 251 , cerebral amyloid angiopathy claim 251 , inclusion body myositis claim 251 , macular degeneration claim 251 , MCI claim 251 , or Down's syndrome.253. The method according to claim 251 , wherein amyloid fibril formation or deposition claim 251 , neurodegeneration claim 251 , microglial inflammatory response claim 251 , or cellular toxicity is reduced or inhibited upon administration of said compound.254. The method according to claim 251 , wherein said amyloid-related disease is diabetes claim 251 , AA amyloidosis claim 251 , AL amyloidosis claim 251 , or hemodialysis related amyloidosis (βM).255. The method of claim 251 , wherein said subject has Alzheimer's disease claim 251 , Mild Cognitive Impairment claim 251 , or cerebral amyloid angiopathy claim 251 , and stabilization of cognitive function claim 251 , prevention of a further decrease in cognitive function claim 251 , or prevention claim 251 , slowing claim 251 , or stopping of disease progression occurs in said patient upon administration.256. A method for inhibiting amyloid deposition in a subject comprising administering ...

ARYL SUBSTITUTED INDOLES AND THE USE THEREOF

The invention relates to aryl and heteroaryl substituted compounds of Formula (I), and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein G, R, and Z-Zare defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain. 160-. (canceled)62. (canceled)6474-. (canceled)75. A pharmaceutical composition claim 61 , comprising the compound of claim 61 , or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof claim 61 , and a pharmaceutically acceptable carrier.7679-. (canceled)80. A method for treating pain in a mammal claim 61 , comprising administering an effective amount of a compound as claimed in or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof claim 61 , to a mammal in need of such treatment.81. (canceled)82. The method of claim 80 , wherein the method is for preemptive or palliative treatment of pain.83. The method of claim 80 , wherein said pain is selected from the group consisting of chronic pain claim 80 , inflammatory pain claim 80 , neuropathic pain claim 80 , postsurgical pain claim 80 , acute pain claim 80 , and surgical pain.84. A method of modulating sodium channels in a mammal claim 61 , comprising administering to the mammal at least one compound as claimed in or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof claim 61 , wherein Na1.7 sodium channel is modulated.85. (canceled)86. A compound as claimed in claim 61 , wherein the compound is H claim 61 , C claim 61 , or C radiolabeled claim 61 , or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof.8791-. (canceled)92. A pharmaceutical composition claim 63 , comprising the compound of claim 63 , or a pharmaceutically acceptable salt claim 63 , prodrug or solvate thereof claim 63 , and a pharmaceutically ...

"MULTI-TARGET" COMPOUNDS WITH INHIBITORY ACTIVITY TOWARDS HISTONE DEACETYLASES AND TUBULIN POLYMERISATION, FOR USE IN THE TREATMENT OF CANCER

The present invention relates to the design of novel molecules, referred to as “multi-target” molecules, having a double pharmacophore and acting both as inhibitors of histone deacetylases (HDACs) and as inhibitors of tubulin polymerisation. The invention also describes the method for synthesising the “multi-target” molecules and their use in the treatment of cancer, a pharmaceutical composition comprising at least one “multi-target” molecule, and the use of such compositions in the treatment of cancer. 119.-. (canceled)33. A pharmaceutical composition comprising at least one compound of formula (I) as defined in claim 20 , or a pharmaceutically acceptable salt thereof claim 20 , in combination with one or more pharmaceutically acceptable excipients.34. The pharmaceutical composition according to claim 33 , further comprising at least one other active principle claim 33 , selected from 6-mercaptopurine claim 33 , fludarabine claim 33 , cladribine claim 33 , pentostatin claim 33 , cytarabine claim 33 , 5-fluorouracil claim 33 , gemcitabine claim 33 , methotrexate claim 33 , raltitrexed claim 33 , irinotecan claim 33 , topotecan claim 33 , etoposide claim 33 , daunorubicin claim 33 , doxorubicin claim 33 , epirubicin claim 33 , idarubicin claim 33 , pirarubicin claim 33 , mitoxantrone claim 33 , chlormethine claim 33 , cyclophosphamide claim 33 , ifosfamide claim 33 , melphalan claim 33 , chlorambucil claim 33 , busulfan claim 33 , carmustine claim 33 , fotemustine claim 33 , streptozocine claim 33 , carboplatin claim 33 , cisplatin claim 33 , oxaliplatin claim 33 , procarbazine claim 33 , dacarbazine claim 33 , bleomycin claim 33 , vinblastine claim 33 , vincristine claim 33 , vindesine claim 33 , vinorelbine claim 33 , paclitaxel claim 33 , docetaxel claim 33 , L-asparaginase claim 33 , flutamide claim 33 , nilutamide claim 33 , bicalutamide claim 33 , cyproterone acetate claim 33 , triptorelin claim 33 , leuprorelin claim 33 , goserelin claim 33 , buserelin claim ...

METHODS OF PROTECTING AGAINST NEURODEGENERATION

The disclosure provides a method of preventing or reducing protein aggregates using combretastatin-A4 (CA4) or an analog thereof. The disclosure also provides methods of reducing the risk, delaying the onset, delaying or slowing the progression, or reversing the signs or symptoms of a neurodegenerative (or other age-progressive) disease using a combretastatin-A4 (CA4) or an analog thereof. The combretastatin-A4 (CA4) or an analog thereof may bind glial fibrillary acidic protein (GFAP). The combretastatin-A4 (CA4) or an analog thereof is described by compounds of Formula (I). 1. A method to prevent or reduce protein aggregates in the central nervous system of a subject , the method comprising administering to the subject a composition comprising a compound that binds glial fibrillary acidic protein (GFAP).2. The method of claim 1 , wherein the compound also binds tubulin β chain (TUBB) claim 1 , myelin basic protein (MPB) claim 1 , histone H2B (H2B3B) claim 1 , and/or α-crystallin B chain (CRYAB).3. The method of claim 1 , wherein the protein aggregates contain or are initiated by Aβ1-42 claim 1 , β-amyloid claim 1 , α-synuclein claim 1 , and/or a polyglutamine array expansion protein.4. (canceled)6. (canceled)7. The method of claim 5 , wherein R claim 5 , R claim 5 , R claim 5 , and Rare independently selected from hydrogen claim 5 , hydrocarbyl claim 5 , substituted hydrocarbyl claim 5 , alkylalkylamino claim 5 , amidine claim 5 , amino claim 5 , carboxyl claim 5 , cyano claim 5 , ester claim 5 , halogen claim 5 , hydroxyl claim 5 , and nitro.8. The method of claim 7 , wherein R claim 7 , R claim 7 , R claim 7 , and Rare hydrogen.9. The method of claim 5 , wherein R claim 5 , R claim 5 , R claim 5 , R claim 5 , and Rare independently selected from hydrogen claim 5 , hydrocarbyl claim 5 , substituted hydrocarbyl claim 5 , alkylalkylamino claim 5 , amidine claim 5 , amino claim 5 , carboxyl claim 5 , cyano claim 5 , ester claim 5 , halogen claim 5 , hydroxyl claim 5 ...

INHIBITORS OF HISTONE LYSINE SPECIFIC DEMETHYLASE (LSD1) AND HISTONE DEACETYLASES (HDACS)

A series of phenelzine analogs comprising a phenelzine scaffold linked to an aromatic moiety and their use as inhibitors of lysine-specific demethylase 1 (LSD1) and/or one or more histone deacetylases (HDACs) is provided. The presently disclosed phenelzine analogs exhibit potency and selectivity for LSD1 versus MAO and LSD2 enzymes and exhibit bulk, as well as, gene specific histone methylation changes, anti-proliferative activity in several cancer cell lines, and neuroprotection in response to oxidative stress. Accordingly, the presently disclosed phenelzine analogs can be used to treat diseases, conditions, or disorders related to LSD1 and/or HDACs, including, but not limited to, cancers and neurodegenerative diseases. 13. A pharmaceutical composition comprising a compound of Formula (I) or Formula (II).14. The pharmaceutical composition of claim 13 , further comprising one or more additional therapeutic agents.15. The pharmaceutical composition of claim 14 , wherein the one or more additional therapeutic agents is selected from the group consisting of a histone deacetylase (HDAC) inhibitor claim 14 , a DNA methyltransferase (DNMT) inhibitor claim 14 , and combinations thereof.16. A method for inhibiting lysine-specific demethylase 1 (LSD1) and/or one or more histone deacetylases (HDACs) claim 14 , the method comprising administering to a subject a compound of Formula (Ia) or a compound of Formula (II) claim 14 , or a pharmaceutically acceptable salt thereof claim 14 , in an amount effective to inhibit LSD1 or one or more HDACs.17. A method for treating a disease claim 14 , disorder claim 14 , or condition associated with lysine-specific demethylase 1 (LSD1) and/or one or more histone deacetylases (HDACs) claim 14 , the method comprising administering to a subject in need of treatment thereof subject a compound of Formula (Ia) or Formula (II) claim 14 , or a pharmaceutically acceptable salt thereof claim 14 , in an amount effective to inhibit LSD1 and/or one or ...

Allenamide as an orthogonal handle for selective modification of cysteine in peptides and proteins

There is provided a compound of formula I, having the structure: wherein R 1 to R 5 have the meanings given in the description.

Modulators of atp-binding cassette transporters

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

Sepiapterin reductase inhibitors for the treatment of pain

Disclosed herein are small molecule heterocyclic inhibitors of sepiapterin reductase (SPR), and prodrugs and pharmaceutically acceptable salts thereof. The Also featured are pharmaceutical compositions of the compounds and uses of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, and neuropathic pain).

PPARG MODULATORS FOR TREATMENT OF OSTEOPOROSIS

The invention provides methods of treatment of a progressive bone disease, such as osteoporosis, Paget's Disease, multiple myeloma, or hyperparathyroidism, comprising administration of an effective amount of a non-agonist PPARG modulator to a patient afflicted with the disease. 2. The method of claim 1 , wherein Yor Yare each C and Rand Rare independently H or methyl.3. The method of claim 1 , wherein Yis N and Yis C claim 1 , or wherein Yis C and Yis N.4. The method of claim 1 , wherein Ris benzyl claim 1 , α-phenethyl claim 1 , α-phenpropyl claim 1 , cycloalkyl or cycloalkylalkyl claim 1 , any of which is unsubstituted or substituted.5. The method of claim 1 , wherein Ris heterocyclyl claim 1 , heterocyclylalkyl claim 1 , heteroaryl claim 1 , or heteroarylalkyl claim 1 , any of which is unsubstituted or substituted.7. The method of claim 1 , wherein YRRis SO.8. The method of claim 1 , wherein Y is C-alkyl; and Rand Rare H claim 1 , or wherein Y is C-alkyl claim 1 , and Rand Rare H.10. The method of claim 1 , wherein for the compound of formula (I) claim 1 , no Z group is present on the ring comprising X-X claim 1 , providing a compound of formula (IA).12. The method of claim 1 , wherein for the compound of formula (I) claim 1 , Z is present claim 1 , providing a compound of formula (IB).13. The method of claim 12 , wherein Z-Zare all carbon.15. The method of claim 1 , wherein the progressive bone disease is osteoporosis claim 1 , Paget's Disease claim 1 , multiple myeloma claim 1 , or hyperparathyroidism.16. The method of claim 1 , wherein administration of the compound of formula (I) acts to increase FGF21 while increasing bone health.18. The use of claim 17 , wherein the progressive bone disease is osteoporosis claim 17 , Paget's Disease claim 17 , multiple myeloma claim 17 , or hyperparathyroidism.19. The use of claim 17 , wherein administration of the compound of formula (I) acts to increase FGF21 while increasing bone health. This application claims the ...

Fullerene Derivatives and Their Applications in Organic Photovoltaics

The present invention relates to new fullerene derivatives of formulae 1a-d, 2 and 3: method of synthesizing said derivatives, and applications thereof in organic photovoltaics, e.g., organic solar cells. In particular, the fullerene derivatives of the present invention are soluble in non-halogenated solvents such that an environmental-friendly and low-cost fabrication method for industrialization of solar cell based on the new fullerene derivatives is provided. An ink formulation for forming a thin film on a substrate of organic photovoltaics comprising at least one of the fullerene derivatives of the present invention is also provided. Greater than 3% power conversion efficiency of the organic solar cells (area=0.16 cm 2 ) formed based on the fullerene derivatives of the present invention with less pollution and lower cost in fabrication can be achieved in the present invention.

RADIOPROTECTOR COMPOUNDS

Radioprotector compounds including 3,3′-diindolylmethane (DIM) analogs, are provided. Further provided are methods for their use in reducing or preventing radiation damage, killing a tumor cell and protecting a non-tumor cell, and treating cancer. 3. (canceled)6. (canceled)7. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. (canceled)17. (canceled)18. (canceled)19. (canceled)21. A composition comprising one or more of the compounds according to and a pharmaceutically acceptable carrier.23. The method of claim 21 , further comprising administering a second therapeutic agent to the subject.24. The method of claim 23 , wherein the second therapeutic agent is a radioprotector compound.25. The method of claim 23 , wherein the second therapeutic agent is 3 claim 23 ,3′-diindolylmethane (DIM).27. The method of claim 26 , wherein the irradiating step is performed prior to the administering step or wherein the administering step is performed prior to the irradiating step.28. (canceled)29. (canceled)30. (canceled)31. The method of claim 26 , wherein the tumor cell is a BRCA-deficient tumor cell.33. The method of claim 32 , wherein the cancer is breast cancer or ovarian cancer.34. The method of claim 33 , wherein the breast cancer is BRCA-deficient breast cancer.35. The method of claim 33 , wherein the ovarian cancer is BRCA-deficient ovarian cancer.36. A method of reducing radiation damage in a subject claim 33 , comprising:administering to the subject an effective amount of 3,3′-diindolylmethane (DIM) after exposure of the subject to radiation.37. The method of claim 36 , wherein the DIM is administered to the subject at least 24 hours after exposure of the subject to radiation.38. A method of reducing or preventing radiation damage in a subject claim 36 , comprising:administering to the subject an effect amount of 3,3′-diindolylmethane (DIM),wherein the DIM is microencapsulated.39. The method of claim 36 , wherein the DIM is ...

Augmenting Moieties for Anti-Inflammatory Compounds

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

MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The present invention features a compound of formula I: 155.-. (canceled)57. The compound claim 56 , salt claim 56 , or deuterated derivative of claim 56 , wherein ring B is phenyl claim 56 , pyridyl claim 56 , pyridine-2(1H)-one claim 56 , pyrazole claim 56 , indole claim 56 , thiophene claim 56 , dihydrobenzofuran claim 56 , pyrazine claim 56 , indazole claim 56 , thiazole claim 56 , pyridine-4(1H)-one claim 56 , pyrrolidinone claim 56 , or quinoline.59. The compound claim 56 , salt claim 56 , or deuterated derivative of claim 56 , wherein ring C is phenyl claim 56 , indole claim 56 , cycloalkyl claim 56 , pyridyl claim 56 , pyrrolidine claim 56 , naphthalene claim 56 , or dihydroindene.61. The compound claim 56 , salt claim 56 , or deuterated derivative of claim 56 , wherein Y is O.62. The compound claim 56 , salt claim 56 , or deuterated derivative of claim 56 , wherein Y is CH.63. The compound claim 56 , salt claim 56 , or deuterated derivative of claim 56 , wherein Y is CH(C1-C6 aliphatic).64. The compound claim 56 , salt claim 56 , or deuterated derivative of claim 56 , wherein Y is CH(CH).65. The compound claim 56 , salt claim 56 , or deuterated derivative of claim 56 , wherein Y is CH(CHCH).66. The compound claim 56 , salt claim 56 , or deuterated derivative of claim 56 , wherein Ris halo claim 56 , CN claim 56 , C1-C6 aliphatic claim 56 , C1-C6alkoxy claim 56 , C3-C8 cycloalkyl claim 56 , or a phenyl claim 56 , pyridyl claim 56 , pyrimidine claim 56 , indole claim 56 , aza-indole claim 56 , or thiophene ring claim 56 , wherein all rings may be substituted with halo claim 56 , C1-C6 aliphatic claim 56 , C1-C6 alkoxy claim 56 , C1-C6 fluoroaliphatic claim 56 , C1-C6 fluoroalkoxy claim 56 , OH claim 56 , CHOH claim 56 , CHOCH claim 56 , CN claim 56 , COH claim 56 , amino claim 56 , amido claim 56 , C3-C10 heteroaryl claim 56 , C3-C10 heterocycloalkyl claim 56 , or a (C1-C8 aliphatic)-Rwherein up to three CHunits may be replaced with O claim 56 , CO claim 56 , ...

NOVEL COMPOUNDS AND COMPOSITIONS FOR INHIBITION OF FASN

The present invention relates to compounds and composition for inhibition of FASN, their synthesis, applications, and antidotes. An illustrative compound of the invention is shown below: 6. The compound of claim 2 , wherein A and B are O.10. The compound of claim 2 , wherein Aris a substituted or unsubstituted 5-6 membered monocycle aryl or heteroaryl.11. The compound of claim 10 , wherein Aris a substituted or unsubstituted 5 membered monocycle aryl or heteroaryl and said heteroaryl has 1 or 2 heteroatoms which are independently S or N.13. The compound of claim 10 , wherein Aris a substituted or unsubstituted 6 membered monocycle aryl or heteroaryl and said heteroaryl has 1 or 2 heteroatoms which are N.18. The compound of claim 2 , wherein Aris a substituted or unsubstituted 9 membered 6 claim 2 ,5- bicyclic heteroaryl and said heteroaryl has 1 claim 2 , 2 claim 2 , or 3 heteroatoms which are independently O claim 2 , S or N.20. The compound of claim 2 , wherein Ris a substituted or unsubstituted monocycle or bicyclic 5-10 membered aryl or heteroaryl.21. The compound of claim 20 , wherein Ris a substituted or unsubstituted monocylic 6 membered aryl.23. The compound of claim 20 , wherein Ris a substituted or unsubstituted bicyclic 8-10 membered aryl or 8-10 membered heteroaryl.24. The compound of claim 23 , wherein Ris a substituted or unsubstituted 8 membered 5 claim 23 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 23 , 2 claim 23 , 3 claim 23 , or 4 heteroatoms and said heteroatoms are independently O claim 23 , S claim 23 , or N.26. The compound of claim 20 , wherein Ris a substituted or unsubstituted 9 membered 6 claim 20 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 20 , 2 claim 20 , 3 claim 20 , or 4 heteroatoms and said heteroatoms are independently O claim 20 , S claim 20 , or N.28. The compound of claim 20 , wherein Ris a substituted or unsubstituted 10 membered 6 claim 20 ,6 bicyclic aryl or heteroaryl and said heteroaryl has 1 claim 20 , ...

NUCLEAR RECEPTOR MODULATORS

The invention provides compounds of Formula (I) 131.-. (canceled)33. A pharmaceutical composition comprising a compound of claim 32 , or a pharmaceutically acceptable salt thereof claim 32 , and one or more pharmaceutically acceptable excipients. This application is a continuation of U.S. application Ser. No. 15/176,309, filed Jun. 8, 2016, the contents of which are incorporated herein by reference. U.S. application Ser. No. 15/176,309 claims the benefit of U.S. Provisional Application No. 62/257,806, filed on Nov. 20, 2015; and U.S. Provisional Application No. 62/343,905, filed on Jun. 1, 2016. This application also claims the benefit of International Application No. PCT/IB2015/001693, filed on Jun. 9, 2015. The entire contents of each of the aforementioned applications are incorporated herein by reference.The present invention relates to novel compounds which modulate the activity of Rorc and the RORγt receptor, and their use as medicaments.The retinoic acid-related orphan receptor (ROR) isoforms RORα, RORβ, and RORγ are members of the steroid nuclear hormone receptor superfamily, and play prominent roles in a variety of biological processes including organ development, immunity, lipid homeostatsis and metabolism, and circadian rhythms (Jetten et al. 2009, 7, 1). The ROR family members are composed of both a ligand-binding domain (LBD) and a DNA-binding domain (DBD). Ligand binding causes a conformational change that modulates binding of co-regulatory proteins: agonists recruit co-activators; antagonists and inverse agonists disrupt the binding of co-activators or enhancing the binding of co-repressors thereby repressing the transcription of target genes (Fauber et al. 2014, 57, 5871).Retinoic acid-related orphan receptor γ thymus (RORγ, also referred to as RORc and NR1F3) is encoded by Rorc; human and mouse RORγ share high sequence homology, and nearly identical binding site homology (Jin, L. et al. 2010, 24, 923). Mammalian RORγ exists in two distinct isoforms, ...

Modulators of atp-binding cassette transporters

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

Use of Indolyl and Indolinyl Hydroxamates for Treating Heart Failure of Neuronal Injury

Novel use of small molecules, particularly indolyl and indolinyl hydroxamates is disclosed herein. The indolyl and indolinyl hydroxamates are useful as lead compounds for manufacturing a medicament or a pharmaceutical composition for treating a patient suffering from heart failure or neuronal injury. 2. The compound of claim 1 , wherein each C claim 1 , X claim 1 , Xand Xare independently H; B is SOR; and Xis CH═CHC(O)NHOH.3. The compound of claim 1 , wherein the heart failure is caused by any of cardiac fibrosis claim 1 , hypertension claim 1 , myocardial infarction claim 1 , myocardial ischaemia claim 1 , dilated cardiomyopathy claim 1 , hypertrophic cardiomyopathy claim 1 , restrictive cardiomyopathy claim 1 , stress cardiomyopathy claim 1 , diabetic cardiomyopathy claim 1 , or idiopathic cardiomyopathy.4. The compound of claim 3 , wherein the heart failure is caused by cardiac fibrosis or hypertension.5. The compound of claim 1 , wherein the neuronal injury is traumatic brain injury or ischemic stroke.6. A method of treating a subject suffering from heart failure or neuronal injury comprising administering to the subject an effective amount of the compound of .7. The method of claim 6 , wherein each C claim 6 , X claim 6 , Xand Xare independently H; B is SOR; and Xis CH═CHC(O)NHOH.8. The method of claim 6 , wherein the subject is a human.9. The method of claim 6 , wherein the heart failure is caused by any of cardiac fibrosis claim 6 , hypertension claim 6 , myocardial infarction claim 6 , myocardial ischaemia claim 6 , dilated cardiomyopathy claim 6 , hypertrophic cardiomyopathy claim 6 , restrictive cardiomyopathy claim 6 , stress cardiomyopathy claim 6 , diabetic cardiomyopathy claim 6 , or idiopathic cardiomyopathy.10. The method of claim 9 , wherein the heart failure is caused by cardiac fibrosis or hypertension.11. The method of claim 6 , wherein the neuronal injury is traumatic brain injury or ischemic stroke.13. The compound of claim 12 , wherein the ...

DIPEPTIDOMIMETICS AS INHIBITORS OF HUMAN IMMUNOPROTEASOMES

The compounds of the present invention are represented by the following compounds having Formula I: 17.-. (canceled)15. The method of claim 8 , wherein an autoimmune disorder is treated claim 8 , said autoimmune disorder being selected from the group consisting of arthritis claim 8 , colitis claim 8 , multiple sclerosis claim 8 , lupus claim 8 , systemic sclerosis claim 8 , and sjögren syndrome.16. The method of claim 8 , wherein immunosuppression is provided for transplanted organs or tissues claim 8 , said immunosuppression being used to prevent transplant rejection and graft-verse-host disease.17. The method of claim 8 , wherein an inflammatory disorder is treated claim 8 , said inflammatory disorder being Crohn's disease and ulcerative colitis.18. The method of claim 8 , wherein cancer is treated claim 8 , said cancer being selected from the group consisting of neoplastic disorders claim 8 , hematologic malignancies claim 8 , and lymphocytic malignancies.1926.-. (canceled)34. The method of claim 27 , wherein an autoimmune disorder is treated claim 27 , said autoimmune disorder being selected from the group consisting of arthritis claim 27 , colitis claim 27 , multiple sclerosis claim 27 , and lupus.35. The method of claim 27 , wherein immunosuppression is provided for transplanted organs or tissues claim 27 , said immunosuppression being used to prevent transplant rejection and graft-verse-host disease.36. The method of claim 27 , wherein an inflammatory disorder is treated claim 27 , said inflammatory disorder being Crohn's disease.37. The method of claim 27 , wherein cancer is treated claim 27 , said cancer being selected from the group consisting of neoplastic disorders claim 27 , hematologic malignancies claim 27 , and lymphocytic malignancies.38. (canceled) This application claims the benefit of U.S. Provisional Patent Application Ser. No. 62/038,636, filed Aug. 18, 2014, which is hereby incorporated by reference in its entirety.This invention was made with ...

Non-Lactone Carbocyclic and Heterocyclic Antagonists and Agonists of Bacterial Quorum Sensing

Compounds which modulate quorum sensing in quorum sensing bacteria. Compounds of the invention inhibit quorum sensing and/or activate quorum sensing in various bacteria. Compounds that inhibit quorum sensing are particularly useful for inhibition of detrimental bacterial biofilm formation. Compounds that activate quorum sensing are particularly useful for promoting growth and biofilm formation of beneficial bacterial. 120.-. (canceled)22. The compound of wherein HG is a phenyl ring substituted with one or more of nitro claim 21 , nitrile or azide.23. The compound of wherein HG is a phenyl ring substituted with a nitro group.25. The compound of wherein Y is —CO— or —CO—CH—CO—.26. The compound of wherein W is —NH— and Y is —NH—CO— claim 22 , —CO—CH—C(Y1)- or —SO— claim 22 , where Y1 is —OH claim 22 , —SH claim 22 , —NHor —F;28. The compound of wherein A is an aryl or heteroaryl group.29. The compound of where n is 0 claim 28 , p1 is 1 and A is an optionally substituted phenyl group.30. The compound of where A is a phenyl ring carrying at least one non-hydrogen substituent.31. The compound of where the at least one non-hydrogen substituent is selected from the group consisting of halogen claim 30 , nitro claim 30 , optionally substituted alkyl having 1 to 3 carbon atoms claim 30 , optionally substituted alkoxy having 1 to 3 carbon atoms claim 30 , optionally substituted thioalkoxy claim 30 , optionally substituted phenyl claim 30 , wherein optional substitution is substitution with one or more halogens claim 30 , nitro claim 30 , hydroxyl claim 30 , alkyl having 1-3 carbon atoms claim 30 , and alkoxy having 1-3 carbon atoms.32. A compound of having formula:{'br': None, 'sub': '2', 'A-CO—CH—CO—NH-HG'}wherein A is an alkyl group having 9 to 12 carbon atoms and HG is a phenyl group substituted with one or more substituents selected from the group consisting of halogen, nitro, hydroxyl, nitrile, azide, —R, or —OR wherein R is an alkyl group having 1-6 carbon atoms.33. A ...

COMBRETASTATIN ANALOGS

The present invention relates novel heterocyclic analogs of combretastatin, their synthesis, and their use as anti-cancer compounds. In particular, compounds of Formula (I), Formula (II), and Formula (V) are provided. 113.-. (canceled)15. The process of claim 14 , wherein the compound comprising Formula (III) is chosen from benzo[b]thiophene-2-carbaldehydes claim 14 , benzo[b]thiophene-3-carbaldehydes claim 14 , benzofuran-2-carboxaldehydes claim 14 , benzofuran-3-carboxaldehydes claim 14 , indole-2-carboxaldehydes claim 14 , indole-3-carboxaldehydes claim 14 , and benzthiazole-2-carboxaldehydes.16. The process of claim 14 , wherein the phenyl acetonitrile is chosen from 3 claim 14 ,4 claim 14 ,5-trimethoxy phenylacetonitrile claim 14 , 3 claim 14 ,4-di methoxyphenylacetonitrile claim 14 , and 4-hydroxy claim 14 , 3 claim 14 ,5-trimethoxyphenylacetonitrile.17. The process of claim 14 , wherein the phenyl triphenyl phosphine is chosen from 3 claim 14 ,4 claim 14 ,5 trimethoxy phenyltriphenyl phosphine bromide claim 14 , 3 claim 14 ,4-dimethoxy phenyltriphenyl phosphine bromide claim 14 , 4-hydroxy claim 14 , and 3 claim 14 ,5-dimethoxyphenyltriphenyl phosphine bromide.18. The process of claim 14 , wherein the base is a methoxide base.1949.-. (canceled)51. The compound of claim 50 , wherein R claim 50 , R claim 50 , R claim 50 , and Rare hydrogen.52. The compound of claim 50 , wherein Ris chosen from hydrogen claim 50 , cyano claim 50 , and carboxyl claim 50 , and Ris hydrogen.53. The compound of claim 50 , wherein R claim 50 , R claim 50 , and Rare independently chosen from hydrogen claim 50 , methoxy claim 50 , ethoxy claim 50 , benzyloxy claim 50 , substituted benzyloxy claim 50 , hydroxyl claim 50 , and lower alkyl groups.54. The compound of claim 15 , wherein R claim 15 , R claim 15 , and Rare independently chosen from hydrogen claim 15 , hydroxyl claim 15 , and methoxy.5550. The compound of cliam claim 15 , wherein X is chosen from C or S.56. The compound of ...

Crystalline polymorphic forms of an antidiabetic compound

The present invention relates to polymorphic forms of a compound of formula A: This compound is useful as a glucagon receptor antagonist and serves as a pharmaceutically active ingredient for the treatment of type 2 diabetes and related conditions, such as hyperglycemia, obesity, dyslipidemia, and the metabolic syndrome. Hydrates, hemihydrates, anhydrates and similar polymorphic forms are included.

Modulators of atp-binding cassette transporters

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

Modulators of atp-binding cassette transporters

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

INDOLE, INDOLINE DERIVATIVES, COMPOSITIONS COMPRISING THEM AND USES THEREOF

The invention provides indole and indoline derivatives and slats thereof, compositions comprising them and uses thereof for the treatment of diseases and disorders. 138-. (canceled)43. A compound according to claim 39 , wherein substituent —ORis substituted at positions 4 claim 39 , 6 or 7.48. A compound according to claim 39 , being a pharmaceutically acceptable salt thereof.49. A composition comprising at least one compound of .50. A method for the treatment of a disease claim 39 , disorder claim 39 , condition or symptom in a subject associated with the inhibition of at least one of oxidative stress claim 39 , inflammation and cholinesterase claim 39 , said method comprises administering to said subject a compound according to .52. A method according to claim 51 , wherein said disease claim 51 , disorder claim 51 , condition or symptom is selected from at least one of Alzheimer's disease claim 51 , Parkinson's disease claim 51 , ischemic stroke claim 51 , amyotropic lateral sclerosis claim 51 , multiple sclerosis claim 51 , mild cognitive impairment claim 51 , ulcerative colitis claim 51 , Crohn's disease claim 51 , rheumatoid arthritis claim 51 , diabetes claim 51 , cardiac failure claim 51 , chronic liver disease claim 51 , chronic lung disease claim 51 , meningitis claim 51 , infective brain disease claim 51 , complex regional pain syndrome (CRPS) and any combinations thereof. This invention relates to indole and indoline derivatives and slats thereof, compositions comprising them and uses thereof for the treatment of diseases and disorders.Impaired mitochondrial function resulting in the production of reactive oxygen species and oxidative stress plays a key role in the aetiology of Alzheimer's disease (AD). Oxidative stress is accompanied by microglial activation and an increase in the release of nitric oxide (NO) and pro-inflammatory cytokines, which further compromises mitochondrial activity. These pathological changes may also contribute to ...

SirT INHIBITORS THAT BIND TO NAD

Compound of formula (I) 2. The method of claim 1 , wherein Ris halo claim 1 , C-Calkyl claim 1 , C-Chaloalkyl or C-Chaloalkoxy.3. The method of claim 1 , wherein Ris halo or C-Calkyl.4. The method of claim 1 , wherein Ris chloro or methyl.5. The method of claim 1 , wherein the compound is 6-Chloro-2 claim 1 ,3 claim 1 ,4 claim 1 ,9-tetrahydro-1H-carbazole-1-carboxylic acid amide.6. The method of claim 1 , wherein the disease is Huntington's disease claim 1 , Spinalbulbar Muscular Atrophy (SBMA or Kennedy's Disease) Dentatorubropallidoluysian Atrophy (DRPLA) claim 1 , Spinocerebellar Ataxia 1 (SCA1) claim 1 , Spinocerebellar Ataxia 2 (SCA2) claim 1 , Machado-Joseph Disease (MJD; SCA3) claim 1 , Spinocerebellar Ataxia 6 (SCA6) claim 1 , Spinocerebellar Ataxia 7 (SCAT) claim 1 , or Spinocerebellar Ataxia 12 (SCA12).7. The method of claim 1 , wherein the disease is Huntington's disease.8. The method of claim 1 , wherein the compound is present in a composition comprising a racemic mixture of a compound of formula (XI). This application is a continuation of U.S. Ser. No. 12/423,751, filed on Apr. 14, 2009, which is a divisional of U.S. Ser. No. 11/077,664 filed on Mar. 11, 2005, which claims priority under 35 USC §119(e) to U.S. Patent Application Ser. No. 60/502,811, filed on Sep. 12, 2003, U.S. Patent Application Ser. No. 60/531,443, filed on Dec. 19, 2003, and U.S. Patent Application Ser. No. 60/560,509, filed on Apr. 7, 2004, and is a continuation-in-part of U.S. patent application Ser. No. 10/940,269, filed Sep. 13, 2004, the entire contents of each of which are hereby incorporated by reference.The Sir2 protein is a deacetylase which uses NAD as a cofactor (Imai et al., 2000; Moazed, 2001; Smith et al., 2000; Tanner et al., 2000; Tanny and Moazed, 2001). Unlike other deacetylases, many of which are involved in gene silencing, Sir2 is insensitive to histone deacetylase inhibitors like trichostatin A (TSA) (Imai et al., 2000; Landry et al., 2000a; Smith et al., 2000). ...

CRYSTALLINE POLYMORPHIC FORMS OF AN ANTIDIABETIC COMPOUND

The present invention relates to polymorphic forms of a compound of formula A: 211-. (canceled)14. A crystalline polymorphic compound of Form II in accordance with having at least three C13 NMR peaks selected from the group consisting of: 131.51 claim 1 , 130.07 claim 1 , 127.68 claim 1 , 126.30 claim 1 , 123.81 claim 1 , 121.65 claim 1 , 52.57 claim 1 , 39.62 claim 1 , 31.77 claim 1 , and 20.79 ppm.1518-. (canceled)19. A pharmaceutical composition comprised of a polymorphic compound in accordance with in combination with a pharmaceutically acceptable carrier.2023-. (canceled) The present invention relates to novel polymorphic forms of a compound of formula A. This compound is useful as a pharmaceutically active ingredient for the treatment of type 2 diabetes and related conditions, such as hyperglycemia, obesity, dyslipidemia, and the metabolic syndrome.Type 2 diabetes remains a serious medical problem. There is an ongoing need for new treatments that are more effective and that have fewer side effects. Glucagon receptor antagonists are important upcoming medications for the treatment of type 2 diabetes and the present compound is particularly useful in this regard.The present invention relates to polymorphic forms of a compound of formula A:The compound is also known as N-(4-{(1S)-1-[(R)-(4-chlorophenyl)(7-fluoro-5-methyl-1H-indol-3-yl)methyl]butyl}benzoyl)-β-alanine. Compound A has been disclosed in a published PCT patent application, WO2008/042223 published on Apr. 10, 2008. Polymorphic forms of the compound that are particularly useful in the preparation of pharmaceutical products are described herein.The invention also relates to pharmaceutical compositions comprising the polymorphic forms described herein, methods for the preparation thereof and the likeThe present invention provides a process for the preparation of crystalline N-(4-{(1S)-1-[(R)-(4-chlorophenyl)(7-fluoro-5-methyl-1H-indol-3-yl)methyl]butyl}benzoyl)-β-alanine of structural formula A:and ...

Modulators of Cystic Fibrosis Transmembrane Conductance Regulator

The present invention features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R 1 , R 2 , R 3 , W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.

COMPOUND

A compound represented by Formula (I) is provided: 2. The compound according to claim 1 , wherein Ris a nitro group claim 1 , a cyano group claim 1 , —F claim 1 , —OCF claim 1 , —SCF claim 1 , —SF claim 1 , —SF claim 1 , —SO—R(Rrepresents a hydrogen atom claim 1 , an alkyl group having 1 to 25 carbon atoms which may have a substituent claim 1 , or an aromatic hydrocarbon group having 6 to 18 carbon atoms which may have a substituent) claim 1 , a fluoroalkyl group claim 1 , or a fluoroaryl group.3. The compound according to claim 1 , wherein Ris a cyano group.4. The compound according to claim 1 , wherein at least one selected from Rand Ris a cyano group claim 1 , a nitro group claim 1 , —OCF claim 1 , —SCF claim 1 , —SF claim 1 , —CO—O—R claim 1 , —SO—R(Rrepresents a hydrogen atom claim 1 , an alkyl group having 1 to 25 carbon atoms which may have a substituent claim 1 , or an aromatic hydrocarbon group having 6 to 18 carbon atoms which may have a substituent) claim 1 , a fluoroalkyl group claim 1 , or a fluoroaryl group.5. The compound according to claim 1 , wherein at least one selected from Rand Ris a cyano group.6. The compound according to claim 1 , wherein both Rand Rare a cyano group.7. The compound according to claim 1 , wherein Rand Rare each independently an aliphatic hydrocarbon group which may have a substituent.8. The compound according to claim 1 , wherein Rand Rare linked to each other to form a ring.9. The compound according to claim 8 , wherein the ring formed by linking Rand Rto each other is a ring having no unsaturated bond.11. The compound according to claim 10 , wherein the ring Whas a 5 to 7-membered ring structure.12. The compound according to claim 10 , wherein the ring Wis a 6-membered ring structure.13. The compound of claim 1 , wherein λ max≥370 nm claim 1 ,(λ max represents a maximum absorption wavelength [nm] of the compound represented by Formula (I)).14. The compound according to claim 1 , which satisfies Formula (B) claim 1 ,{'br': ...

Organic light-emitting device, and light-emitting material and compound used therefor

An organic light-emitting device having a light-emitting layer containing a compound represented by the general formula below has a high light emission efficiency. In the general formula, at least one of R 1 to R 5 represents a cyano group, at least one of R 1 to R 5 represents a 9-carbazolyl group, a 1,2,3,4-tetrahydro-9-carbazolyl group, a 1-indolyl group or a diarylamino group, and the balance of R 1 to R 5 represents a hydrogen atom or a substituent.

METHODS AND MATERIALS FOR INCREASING OR MAINTAINING NICOTINAMIDE MONONUCLEOTIDE ADENYLYL TRANSFERASE-2 (NMNAT2) POLYPEPTIDE LEVELS

This document provides methods and materials for increasing or maintaining NMNAT2 polypeptide levels within cells. For example, compounds (e.g., organic compounds) having the ability to increase or maintain NMNAT2 polypeptide levels within cells, formulations containing compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for making compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for making formulations containing compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for increasing or maintain NMNAT2 polypeptide levels within cells, and methods for treating mammals (e.g., humans) having a condition responsive to an increase in NMNAT2 polypeptide levels are provided (or for preventing said condition). 2. The method of claim 1 , wherein:{'sup': 1', '2', '4', '3, 'sub': 1-6', '1-6', '1-6', '1-6, 'R, R, and Rare each H; and Ris selected from H, halo, Calkyl, Chaloalkyl, Calkoxy, and Chaloalkoxy;'}{'sup': '1', 'sub': 1-6', '2', '1-6', '1-6, 'Lis Calkylene, which is optionally substituted with 1, 2, or 3 substituents selected from OH, NO, CN, halo, Calkoxy, and Chaloalkoxy;'}{'sup': '5', 'Ris H;'}{'sup': '6', 'sub': '1-6', 'Ris selected from H and Calkyl;'}{'sup': '2', 'sub': 1-6', '2', '1-6', '1-6, 'Lis Calkylene, which is optionally substituted with 1, 2, or 3 substituents selected from OH, NO, CN, halo, Calkoxy, and Chaloalkoxy;'}{'sup': '2', 'or Lis absent;'}{'sup': 7', '1', 'a1', 'c1', 'd1, 'Ris selected from Cy, OR, and NRR;'}{'sup': '1', 'sub': 6-10', '1-6', '1-6', '1-6', '1-6', '1-6', '3-10', '1-6', '6-10', '1-6, 'Cyis selected from: (i) Caryl, optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, Calkyl, Chaloalkyl, Calkoxy, Calkylthio, and C(O)Calkyl; (ii) Ccycloalkyl, optionally substituted with 1 or 2 Calkyl; and (iii) 4-10 membered heterocycloalkyl, optionally substituted with ...

Double-Labeled Probe for Molecular Imaging and Use Thereof

The present invention relates to a compound or a pharmaceutically acceptable salt thereof having a chemical structure comprising: (A) at least one motif specifically binding to cell membranes of neoplastic cells; (B) at least one chelator moiety of radiometals; and (C) at least one dye moiety; wherein said compound has a molecular weight of not more than 5 kDa. Further, the invention refers to a method for producing such compound and to the in vivo and in vitro uses thereof. 1. A compound or a pharmaceutically acceptable salt thereof having a chemical structure comprising:(A) at least one motif specifically binding to cell membranes of neoplastic cells;(B) at least one chelator moiety of radiometals; and(C) at least one dye moiety;wherein said compound has a molecular weight of not more than 5 kDa.2. The compound according to claim 1 , wherein said compound has the following molecular structure:{'br': None, '(A)-(B)-(C),'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein (A), (B) and (C) are defined as in .'}3. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein said compound has the following molecular structure:{'br': None, '(A)-(B)-(C),'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein (A), (B) and (C) are defined as in , wherein (B) and (C) and (A) and (B) are conjugated with another via a spacer molecule.'}4. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein said compound has the following molecular structure:{'br': None, '(A)-(B)-(C),'}wherein the “-” is a bond via a spacer molecule or a direct bond.5. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein said compound has the following molecular structure:{'br': None, '(A)-x-(B)-y-(C),'}wherein x and y represent independently from another each a spacer molecule.6. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the motif specifically ...

MARMELIN ANALOGS AND METHODS OF USE IN CANCER TREATMENT

A pharmaceutical composition can include: a marmelin analog compound, and a pharmaceutically acceptable carrier having the compound. The compound can be present in a therapeutically effective amount to treat or inhibit a disease state. The disease state can be cancer. The cancer can be selected from brain cancers, head and neck cancers, thyroid cancers, gastrointestinal cancers, esophageal cancers, stomach cancers, pancreatic cancers, liver cancers, colo-rectal cancers, lung cancers, kidney cancers, prostate cancers, bladder cancers, testicular cancers, breast cancers, ovarian cancers, cervical cancers, and melanomas. The carrier includes a cyclodextrin, which may form a complex with the compound. The compounds and compositions can be used to treat or inhibit progression of cancers. Colo-rectal, bladder, and prostate cancers are examples of some of the cancers that can be treated with the marmelin analog compounds. 2. The compound of claim 1 , wherein:{'sup': '2', 'Rincludes one or more of a hydrogen, halogens, hydroxyls, alkoxys, straight aliphatics, branched aliphatics, cyclic aliphatics, substituted aliphatics, unsubstituted aliphatics, saturated aliphatics, unsaturated aliphatics, aromatics, polyaromatics, substituted aromatics, hetero-aromatics, amines, primary amines, secondary amines, tertiary amines, aliphatic amines, thios, sulfhydryls, phosphors, carbonyls, carboxyls, amides, esters, amino acids, peptides, polypeptides, derivatives thereof, substituted or unsubstituted, or combinations thereof.'}3. The compound of claim 1 , wherein Rincludes one or more of hydrogen claim 1 , C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , C-Caryl claim 1 , C-Calkaryl claim 1 , C-Caralkyl claim 1 , halo claim 1 , hydroxyl claim 1 , sulfhydryl claim 1 , C-Calkoxy claim 1 , C-Calkenyloxy claim 1 , C-Calkynyloxy claim 1 , C-Caryloxy claim 1 , acyl claim 1 , C-Calkylcarbonyl (—CO-alkyl) claim 1 , C-Carylcarbonyl (—CO-aryl) claim 1 , acyloxy (—O-acyl) claim 1 , C- ...

SUBSTITUTED-INDOLE-COMPOUNDS AS ESTROGEN RECEPTOR DOWN-REGULATORS

Disclosed is a new indole compound, in particular, the compound as shown in formula (I), and a preparation method, pharmaceutical composition and use thereof as an estrogen receptor down-regulator in preparing drugs for treating estrogen receptor-positive breast cancer. 3. The compound claim 2 , the pharmaceutically acceptable salt claim 2 , the hydrate or the prodrug thereof as defined in claim 2 , wherein claim 2 , R is selected from H claim 2 , F claim 2 , Cl claim 2 , Br claim 2 , I claim 2 , OH claim 2 , CN claim 2 , NH claim 2 , COOH claim 2 , or the group consisting of Calkyl claim 2 , Cheteroalkyl claim 2 , Ccycloalkyl-Calkyl- claim 2 , each of which is optionally substituted with 1 claim 2 , 2 claim 2 , or 3 R′.6. The compound claim 1 , the pharmaceutically acceptable salt claim 1 , the hydrate or the prodrug thereof as defined in claim 1 , wherein claim 1 , R is selected from H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , OH claim 1 , CN claim 1 , NH claim 1 , COOH claim 1 , or the group consisting of Calkyl claim 1 , Cheteroalkyl and Ccycloalkyl-Calkyl- claim 1 , each of which is optionally substituted with 1 claim 1 , 2 claim 1 , or 3 R′.13. (canceled)16. (canceled)17. The compound claim 12 , the pharmaceutically acceptable salt claim 12 , the hydrate or the prodrug thereof as defined in claim 12 , wherein claim 12 , Rand Rare each independently selected from the group consisting of H claim 12 , F claim 12 , Cl claim 12 , Br claim 12 , CN and CH.18. (canceled)21. (canceled)27. A pharmaceutical composition comprising a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof as defined in and a pharmaceutically acceptable carrier.28. A method for treating a disorder associated with estrogen receptor in a subject in need thereof claim 1 , comprising: administrating an effective amount of the compound or the pharmaceutically acceptable salt thereof as defined in as defined in preparing a medicament for ...

PIPERAZINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO

The disclosure relates to piperazine derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidase. 2. The pharmaceutical composition of claim 1 , wherein Z is C═O.3. The pharmaceutical composition of claim 1 , wherein Ris alkyl substituted with amino wherein the amino is substituted with an aryl group optionally substituted with one or more alkoxy.4. The pharmaceutical composition of claim 1 , wherein Ris a heterocyclyl optionally substituted with one or more R;5. The pharmaceutical composition of claim 3 , wherein the heterocyclyl is indolyl claim 3 , quinolinyl claim 3 , or imidazolyl.6. A compound of formula I as in claim 1 , selected from the group consisting of2-((4-acetylphenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(4-methoxyphenyl)-3-methylpiperazin-1-yl)ethanone;2-((4-isopropylphenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(4-ethoxyphenyl)piperazin-1-yl)ethanone;2-((3,4-difluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((3-fluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(3-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(2-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(4-fluorophenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(2-fluorophenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(pyridin-4-yl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)ethanone;4-(4-(2-((4-acetylphenyl)amino)acetyl)piperazin-1-yl)benzonitrile;2-((2-fluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-fluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(3,4-dimethoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(2-hydroxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl) ...

CYANINE COMPOUNDS

Compounds used as labels with properties comparable to known fluorescent compounds. The compounds can be conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided. 5. A method of labeling at least one biomolecule claim 2 , the method comprising providing a composition comprising at least one excipient and the compound of in an effective concentration to label at least one biomolecule under conditions sufficient for labeling the biomolecule with the compound.6. The method of wherein the biomolecule is selected from the group consisting of a protein claim 5 , antibody claim 5 , enzyme claim 5 , nucleoside triphosphate claim 5 , oligonucleotide claim 5 , biotin claim 5 , hapten claim 5 , cofactor claim 5 , lectin claim 5 , antibody binding protein claim 5 , carotenoid claim 5 , carbohydrate claim 5 , hormone claim 5 , neurotransmitter claim 5 , growth factors claim 5 , toxin claim 5 , biological cell claim 5 , lipid claim 5 , receptor binding drug claim 5 , fluorescent proteins claim 5 , organic polymer carrier material claim 5 , inorganic carrier material claim 5 , and combinations thereof.7. A method of labeling at least one biomolecule claim 3 , the method comprising providing a composition comprising at least one excipient and the compound of in an effective concentration to label at least one biomolecule under conditions sufficient for labeling the biomolecule with the compound.8. The method of wherein the biomolecule is selected from the group consisting of a protein claim 7 , antibody claim 7 , enzyme claim 7 , nucleoside triphosphate claim 7 , oligonucleotide claim 7 , biotin claim 7 , hapten claim 7 , cofactor claim 7 , lectin claim 7 , antibody binding protein claim 7 , carotenoid claim 7 , carbohydrate claim 7 , hormone claim 7 , neurotransmitter claim 7 , growth factors claim 7 , toxin claim 7 , biological ...

COMBRETASTATIN ANALOGS

The present invention relates novel heterocyclic analogs of combretastatin, their synthesis, and their use as anti-cancer compounds. In particular, compounds of Formula (I), Formula (II), and Formula (V) are provided. 2. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , and Rare hydrogen.3. The compound of claim 1 , wherein Ris chosen from hydrogen claim 1 , cyano claim 1 , and carboxyl claim 1 , and Ris hydrogen.4. The compound of claim 3 , wherein Ris hydrogen and Ris cyano.5. The compound of claim 1 , wherein R claim 1 , R claim 1 , and Rare independently chosen from hydrogen claim 1 , methoxy claim 1 , ethoxy claim 1 , benzyloxy claim 1 , substituted benzyloxy claim 1 , hydroxyl claim 1 , and lower alkyl groups.6. The compound of claim 5 , wherein R claim 5 , R claim 5 , and Rare independently chosen from hydrogen claim 5 , hydroxyl claim 5 , and methoxy.7. The compound of claim 6 , wherein R claim 6 , R claim 6 , and Rare independently chosen from hydrogen and methoxy.8. The compound of claim 1 , wherein X is chosen from C or S.9. The compound of claim 1 , wherein Y is chosen from O claim 1 , S claim 1 , and NR.10. The compound of claim 1 , wherein G is Q with the proviso that where Ris cyano claim 1 , Rand Rare not each OCH.11. The compound of claim 10 , wherein Q is chosen from 2-quinolinyl and 3-quinolinyl.12. The compound of claim 10 , wherein Ris hydrogen and Ris cyano.13. The compound of claim 10 , wherein R claim 10 , R claim 10 , R claim 10 , R claim 10 , Rare independently chosen from hydrogen and hydroxyl.14. The compound of claim 10 , wherein R claim 10 , R claim 10 , and Rare independently chosen from hydrogen and hydroxyl.15. The compound of claim 10 , wherein R claim 10 , R claim 10 , and Rare hydroxyl. This application is a divisional of U.S. application Ser. No. 14/785,381, filed Oct. 19, 2015 which claims the benefit of PCT Application PCT/US2014/034185, filed Apr. 15, 2014, which claims the benefit of U.S. Provisional ...

Indole carboxamide compounds

Disclosed are compounds of Formula (I): or a salt thereof, wherein: X is CR 4 or N; R 1 , R 2 , R 3 , R 4 , and A are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

N-substituted isopropyldimethyl azulene sulfonamide derivatives, and preparation method and use thereof

The present invention provides an N-substituted isopropyldimethyl azulene sulfonamide derivative as represented by formula (I), and preparation method and uses thereof, wherein R1 is an alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, amino, or a substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and amino. The N-substituted isopropyldimethyl azulene sulfonamide derivative can be used in treating gastric ulcer.

BENZAMIDE DERIVATIVE, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION COMPRISING SAME AS ACTIVE INGREDIENT FOR PREVENTION OR TREATMENT OF CANCER

The present invention relates to a benzamide derivative, a preparation method therefor, and a pharmaceutical composition comprising same as an active ingredient for prevention or treatment of cancer. The benzamide derivative provided in an aspect of the present invention can be used for preventing or treating cancer by suppressing EGFR mutation, and exhibits a remarkable synergy effect on anticancer activity when administered in combination with an EGFR antagonist such as Cetuximab, thus finding advantageous uses as an anticancer agent. 2. The compound claim 1 , the optical isomer thereof claim 1 , the solvate thereof claim 1 , the hydrate thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein:{'sup': '1', 'sub': '6-12', 'Ris substituted Caryl,'}{'sub': 6-12', '6-12, 'wherein, the substituted Caryl is Caryl substituted with unsubstituted or substituted 5˜10 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S,'}{'sub': 1-10', '1-3', '1-10, 'sup': 4', '5', '4', '5, 'the substituted 5˜10 membered heterocycloalkyl is Cstraight or branched alkylcarbonyl, —NRR, or 5˜10 membered heterocycloalkyl substituted with 6 membered heterocycloalkyl unsubstituted or substituted with one or more Cstraight or branched alkyl containing one or more heteroatoms selected from the group consisting of N, O and S, and Rand Rare independently hydrogen or Cstraight or branched alkyl;'}{'sup': '2', 'Ris halogen;'}{'sup': '3', 'sub': '1-10', 'Ris —OH, or Cstraight or branched alkoxy; and'}X is ═CH—, or ═N—.5. The compound claim 1 , the optical isomer thereof claim 1 , the solvate thereof claim 1 , the hydrate thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is selected from the group consisting of the following:(1) (R)-N-((5-fluoro-2-hydroxyphenyl)(1H-indole-2-yl)methyl)-4′-(piperazine-1-yl)-[1,1′-biphenyl]-3-carboxamide;(2) (R)-4′-(4- ...

Indole-formamide derivative, preparation method therefor and use thereof in medicine

A solid dispersion, a method for preparing same, and a solid preparation comprising the solid dispersion. The solid dispersion contains (R)-4-amino-1-(1-(but-2-ynylacyl)pyrrolidin-3-yl)-3-(4-(2,6-difluorophenoxy)phenyl)-1,6-dihydro-7H-pyrrolo[2,3-d]pyridazine-7-one or a pharmaceutically acceptable salt thereof, and a carrier material. The carrier material is selected from hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate.

MARMELIN ANALOGS AND METHODS OF USE IN CANCER TREATMENT

A pharmaceutical composition can include: a marmelin analog compound, and a pharmaceutically acceptable carrier having the compound. The compound can be present in a therapeutically effective amount to treat or inhibit a disease state. The disease state can be cancer. The cancer can be selected from brain cancers, head and neck cancers, thyroid cancers, gastrointestinal cancers, esophageal cancers, stomach cancers, pancreatic cancers, liver cancers, colo-rectal cancers, lung cancers, kidney cancers, prostate cancers, bladder cancers, testicular cancers, breast cancers, ovarian cancers, cervical cancers, and melanomas. The carrier includes a cyclodextrin, which may form a complex with the compound. The compounds and compositions can be used to treat or inhibit progression of cancers. Colorectal, bladder, and prostate cancers are examples of some of the cancers that can be treated with the marmelin analog compounds. 2. The compound of claim 1 , wherein:{'sup': 1', '2', '3', '4', '5, 'at least one of R, R, R, or R, or Rindependently includes one or more of a hydrogen, halogens, hydroxyls, alkoxys, straight aliphatics, branched aliphatics, cyclic aliphatics, substituted aliphatics, unsubstituted aliphatics, saturated aliphatics, unsaturated aliphatics, aromatics, polyaromatics, substituted aromatics, hetero-aromatics, amines, primary amines, secondary amines, tertiary amines, aliphatic amines, thios, sulfhydryls, phosphors, carbonyls, carboxyls, amides, esters, amino acids, peptides, polypeptides, derivatives thereof, substituted or unsubstituted, or combinations thereof.'}3. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , or Rindependently includes one or more of hydrogen claim 1 , C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , C-Caryl claim 1 , C-Calkaryl claim 1 , C-Caralkyl claim 1 , halo claim 1 , hydroxyl claim 1 , sulfhydryl claim 1 , C-Calkoxy claim 1 , C-Calkenyloxy claim 1 , C-Calkynyloxy claim 1 ...

ANTIMICROBIAL CONJUGATES, METHOD FOR PRODUCTION AND USES THEREOF

The present disclosure relates to polyamine conjugates, its isomers, prodrugs and pharmaceutically acceptable salts thereof. The present disclosure also relates to process of preparation of polyamine conjugates, its stereoisomers, prodrugs, pharmaceutically acceptable salts thereof, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases mediated by microbes. 2. The compound as claimed in or its stereoisomers claim 1 , pharmaceutically acceptable salts claim 1 , polymorphs claim 1 , solvates and hydrates thereof wherein claim 1 , Y is —CH2- or —CO—;{'sub': 1', '2, 'Aand Aare same or different, and independently selected from 2 amino acid residues, wherein the amino acids are independently selected from L-configuration or D-configuration; R is selected from C4-28 alkyl, C6-18 aryl.'}3. The compound as claimed in or its stereoisomers claim 1 , pharmaceutically acceptable salts claim 1 , polymorphs claim 1 , solvates and hydrates thereof wherein claim 1 ,{'sub': 1', '2, 'Aand Aare same or different, and independently selected from 1, 2, 3, or 4 amino acid residues wherein the amino acid residues are independently selected from L-configuration or D-configuration and are positively charged.'}4. The compound as claimed in or its stereoisomers claim 1 , pharmaceutically acceptable salts claim 1 , polymorphs claim 1 , solvates and hydrates thereof wherein claim 1 ,{'sub': '2', 'Y is —CH—;'}{'sup': '1', 'Nis positively charged.'}710-. (canceled)11. A method of treating a disease or condition in a patent claim 1 , said method comprising administering to a patient a compound of formula (I) claim 1 , as claimed in claim 1 , or its stereoisomers claim 1 , pharmaceutically acceptable salts claim 1 , polymorphs claim 1 , solvates and hydrates thereof claim 1 , wherein said disease or condition is caused by microorganism selected from the group consisting of bacteria claim 1 , ...

BIS-INDOLIC DERIVATIVES, THEIR USES IN PARTICULAR AS ANTIBACTERIALS

The present invention relates to novel bis-indolic derivatives, processes for their preparation, and their potential use as new antibacterial drugs. 2. Compounds according to claim 1 , wherein:X and X′ are as previously defined,{'sub': 1', '2', '3', '4', '5', '6', '1', '2', '3', '4', '5', '6, 'R, R, R, R, R, R, R′, R′, R′, R′, R′and R′are as previously defined,'}{'sub': 1', '7', '2', '2', '1', '7', '2', '2', '3', '7', '2', '2', '1', '7', '2', '3', '7', '2', 'n', '2', '2', 'n', '2', '2', 'n', 'a', 'n', '1', '7', '3', '7', '2', 'n', '2', 'n', 'a', 'b', 'a', 'b, 'R represents H, a (C-C)-alkyl, CHNHCO—(C-C)-alkyl, CHNHCO—(C-C)-cycloalkyl, COH, CO—(C-C)-alkyl, CO—(C-C)-cycloalkyl, (CH)OH, CHNH(CH)—OH, CHNH(CH)—NRR, CONH—(C-C)-alkyl, CONH—(C-C)-cycloalkyl, CONH-aryl, CONH—(CH)OH, CONH—(CH)NRR, wherein n=2 to 12 and R, R, aryl and alkyl being as previously defined,'}{'sub': 7', 'a', 'a, 'Rrepresents H, OH, OR, Rbeing as previously defined.'}3. Compounds according to claim 1 , wherein:X and X′ are as previously defined,{'sub': 1', '2', '3', '4', '5', '6', '1', '5', '6, 'R, R, R, R, R, RR′, R′and R′are as previously defined, and'}{'sub': '7', 'R and Rare joined together to form a cycle of formulas (I-a) and (I-b) as previously defined.'}4. Compounds according to claim 1 , wherein the antibacterial activity is against Gram-positive and Gram-negative bacteria.5. Compounds according to claim 1 , wherein said bacteria are resistant to conventional antibiotics.6StaphylococcusStaphylococcus aureusStaphylococcus aureusStaphylococcus aureusStaphylococcus aureus. Compounds according to claim 1 , wherein the antibacterial activity is against species claim 1 , in particular claim 1 , especially resistant to β-lactams (including methicillin-resistant strains claim 1 , also referred as MRSA) claim 1 , resistant to glycopeptides (vancomycin-resistant or glycopeptides-resistant strains claim 1 , also referred as VISA or GISA) and resistant to fluoroquinolones.7. Compounds according to ...

MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS

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

PRIMARY CARBOXAMIDES AS BTK INHIBITORS

The invention provides compounds of Formula (I) 2. The compound according to claim 1 , wherein Y is CR′ and R′ of Y is H claim 1 , optionally substituted ethenyl claim 1 , optionally substituted ethyl claim 1 , optionally substituted methyl claim 1 , optionally substituted 2 claim 1 ,3-dihydrobenzofuranyl claim 1 , optionally substituted 1 claim 1 ,4-dioxanyl claim 1 , optionally substituted 3 claim 1 ,4-dihydro-2H-benzo[b][1 claim 1 ,4]oxazinyl claim 1 , optionally substituted 6 claim 1 ,7-dihydro-4H-pyrazolo[5 claim 1 ,1-c][1 claim 1 ,4]oxazinyl claim 1 , optionally substituted chromanyl claim 1 , optionally substituted cyclohexenyl claim 1 , optionally substituted cyclopropyl claim 1 , optionally substituted tetrahydrofuranyl claim 1 , optionally substituted isochromanyl claim 1 , optionally substituted 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-isoquinolinyl claim 1 , optionally substituted isoxazolyl claim 1 , optionally substituted morpholinyl claim 1 , optionally substituted oxetanyl claim 1 , optionally substituted phenyl claim 1 , optionally substituted piperidinyl claim 1 , optionally substituted piperazinyl claim 1 , optionally substituted 3 claim 1 ,6-dihydro-2H-pyranyl claim 1 , optionally substituted pyrano[4 claim 1 ,3-b]pyridinyl claim 1 , optionally substituted pyrazolyl claim 1 , optionally substituted pyridinyl claim 1 , optionally substituted 3H-pyridin-1-one claim 1 , optionally substituted 1 claim 1 ,2 claim 1 ,3 claim 1 ,6-tetrahydropyridinyl claim 1 , optionally substituted pyrimidinyl claim 1 , optionally substituted pyrrolidinyl claim 1 , optionally substituted 2 claim 1 ,5-dihydropyrrolyl claim 1 , optionally substituted tetrahydropyranyl or optionally substituted tetrahydro-2H-thiopyranyl.3. The compound according to wherein R′ is H or R′ is optionally substituted by one or more substituents independently selected from the group consisting of CN claim 2 , OH claim 2 , ═O claim 2 , halogen claim 2 , (C-C)alkyl claim 2 , (C-C)alkoxy ...

WATER SOLUBLE NOVEL CYANINE FLUOROPHORE WITH TUNABLE PROPERTIES BETWEEN NEAR IR AND SWIR REGION FOR IN VIVO IMAGING

Cyanine fluorophores including a nine-carbon polymethine bridge are disclosed. The cyanine fluorophores have absorbance and/or emission maxima in the near-infrared (NIR) and short-wave infrared (SWIR) wavelength ranges. Methods of making and using the cyanine fluorophores are also disclosed. The compounds are useful in fluorescence imaging, more particularly in cancer treatment. The compounds have generic formula (I): 2. The compound according to claim 1 , wherein:{'sup': 3', '6, '(i) Rand Rare sulfonate; or'}{'sup': 1', '2', '4', '5', '7', '8, '(ii) R, R, R, R, R, and Rare H; or'}(iii) both (i) and (ii).3. The compound according to claim 1 , wherein:{'sup': 9', '10, 'sub': 1', '10, 'Rand Rindependently are C-Calkyl sulfonate; or'}{'sup': 9', '10', 'b', 'b, 'sub': 2', '2', 'n', '1', '3, 'Rand Rare —(CHCHO)Rwhere each n independently is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and each Rindependently is C-Calkyl or H; or'}{'sup': 9', '10, 'sub': 1', '20, 'Rand Rindependently are C-Calkyl.'}4. The compound according to claim 1 , wherein:{'sup': 1', '2', 'c', 'c, 'sub': 2', '1', '3, 'Yand Yare C(R)where each Ris C-Calkyl; or'}{'sup': 1', '2', 'c', 'c, 'sub': '2', 'Yand Yare C(R)where at least one Ris a group comprising a conjugatable moiety, a targeting agent, or a drug; or'}{'sup': 1', '2, 'Yand Yare O.'}5. The compound according to claim 1 , wherein Rand Rtogether with the rings to which they are attached form a fused ring system.7. The compound according to claim 6 , wherein Z′ and Zare O.8. The compound according to claim 6 , wherein:{'sup': 1', '4', '13', '13', '1', '4, 'one of X-Xis CRwhere Ris a group comprising a conjugatable moiety, a targeting agent, or a drug, and the others of X-Xare CH; or'}{'sup': 2', '3', 'e', '2', '3', '1', '4, 'sub': 2', 'p, 'one of Xand Xis C—(CH)C(O)R, the other of Xand Xis CH, and Xand Xare CH; or'}{'sup': 2', '4', '1', '3', '1', '3', '2', '4, 'either Xand Xare C-sulfonate and Xand Xare CH, or Xand Xare C-sulfonate and Xand Xare CH; or'}{' ...

Novel low-molecular-compound for improving production, maintenance and proliferation of pluripotent stem cells, composition comprising the same, and culture method

According to the present invention, when the novel low-molecular-weight compound RSC-133 is added in a culture process for producing reprogrammed pluripotent stem cells from human differentiated cells, it can increase the efficiency of reprogramming and can significantly reduce the time required for the induction of reprogramming. Particularly, the novel compound RSC-133 can substitute for c-Myc acting as both a reprogramming factor and an oncogenic factor, and it can effectively increase the efficiency of reprogramming in both normal oxygen culture conditions and hypoxic culture conditions. In addition, RSC-133 can inhibit the induction of aging occurring in the reprogramming process, exhibits the effect of promoting cell proliferation, and induces epigenetic activation to improve culture conditions for induction of reprogramming. The present invention will contribute to optimizing a process of producing induced pluripotent stem cells from a small amount of patient-specific somatic cells obtained from various sources, and thus it will significantly improve a process of developing clinically applicable personalized stem cell therapy agents and new drugs and will facilitate the practical use of these agents and drugs. In addition, the novel low-molecular-weight compound RSC-133 can provide a cell culture medium effective for maintaining the undifferentiated state of human embryonic stem cells that are typical pluripotent stem cells. The medium composition containing RSC-133 can effectively induce the proliferation of human embryonic stem cells in an undifferentiated state and can be effectively used for the development of a system for culturing large amounts of embryonic stem cells.

HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK

Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus. 138.-. (canceled)40. The method as recited in wherein said disease is chosen from cancer and a metabolic disease.41. The method as recited in wherein said disease is a metabolic disease.42. The method as recited in wherein said metabolic disease is chosen from metabolic syndrome claim 41 , diabetes claim 41 , dyslipidemia claim 41 , fatty liver disease claim 41 , non-alcoholic steatohepatitis claim 41 , obesity claim 41 , and insulin resistance.43. The method of wherein said diabetes is Type II diabetes.44. The method of wherein said dyslipidemia is hyperlipidemia.46. The method of wherein said cholesterol is chosen from LDL and VLDL cholesterol.47. The method of wherein said triglycerides are chosen from plasma triglycerides and liver triglycerides. This application claims the benefit of priority of U.S. Provisional Application No. 61/448,552, filed Mar. 2, 2011, the disclosure of which is hereby incorporated by reference as if written herein in its entirety.Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.The regulation of glycogen metabolism is critical for the maintenance of glucose and energy homeostasis in mammals. Glycogen, a large branched polymer of glucose, acts as a reserve of carbon and energy in a variety of organisms. In mammals, the most important stores are found in the liver and skeletal muscle (1). Liver glycogen is required to efficiently buffer blood glucose levels during fasting, whereas muscle glycogen is primarily used ...

USE OF DERIVATIVES OF INDOLES FOR THE TREATMENT OF CANCER

The present invention relates to the use of derivatives of indoles having a general formula (I) as follow: 115-. (canceled)19. The method according to or , wherein{'sub': '4', 'Rrepresents a nitrile or a carboxamide group, and'}{'sub': 5', '7, 'Rand Rrepresent a hydrogen atom.'}23. The method according to claim 16 , wherein the compound of formula (I) is selected from the group consisting of:(Z)-2-(5-methoxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(5-ethoxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(5-isopropoxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(5-chloro-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(5-fluoro-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(4-methoxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-3-(6-fluoropyridin-3-yl)-2-(5-methoxy-1H-indol-3-yl)-acrylonitrile;(Z)-2-(6-methoxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(1H-indol-3-yl)-3-pyrimidin-5-yl-acrylonitrile;(Z)-2-(5-methoxy-1H-indol-3-yl)-3-pyrimidin-5-yl-acrylonitrile;(Z)-3-(1-cyano-2-(pyridin-3-yl)vinyl)-1H-indol-5-yl-acetate;(Z)-3-(1-cyano-2-(pyridin-3-yl)vinyl)-1H-indol-5-yl 2-methoxyacetate;(Z)-2-(5-benzyloxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-3-(3,5-dimethoxy-phenyl)-2-(5-methoxy-1H-indol-3-yl)-acrylonitrile;(Z)-3-(3,5-dimethoxy-phenyl)-2-(1H-indol-3-yl)-acrylonitrile;(Z)-3-(4-chloro-phenyl)-2-(1H-indol-3-yl)-acrylonitrile;(Z)-2-(5-methoxy-1H-indol-3-yl)-3-pyridin-3-yl-propionitrile;(Z)-3-benzo[1,3]dioxol-5-yl-2-(1H-indol-3-yl)-acrylonitrile;(Z)-3-(1H-indol-3-yl)-2-pyridin-3-yl-acrylonitrile;(Z)-3-(4-fluoro-phenyl)-2-(1H-indol-3-yl)-acrylonitrile;(Z)-2-(5-methoxy-1H-indol-3-yl)-3-pyridin-2-yl-acrylonitrile;(Z)-3-(3-chloro-phenyl)-2-(1H-indol-3-yl)-acrylonitrile;(Z)-3-(4-hydroxy-3,5-dimethoxy-phenyl)-2-(5-methoxy-1H-indol-3-yl)-acrylonitrile;(Z)-2-(1H-indol-3-yl)-3-phenyl-acrylonitrile;(Z)-2-(1H-indol-3-yl-)-3-pyridin-3-yl-propionitrile;(Z)-2-(1H-indol-3-yl)-3-pyridin-2-yl- ...

NOVEL LOW-MOLECULAR-COMPOUND FOR IMPROVING PRODUCTION, MAINTENANCE AND PROLIFERATION OF PLURIPOTENT STEM CELLS, COMPOSITION COMPRISING THE SAME, AND CULTURE METHOD

Provided herein are novel indoleacrylic acid-based compounds, and pharmaceutically acceptable salts thereof, useful for the production, maintenance and proliferation of pluripotent stem cells. Also provided are cell culture compositions comprising these compounds, and methods of using these compounds in the production and maintenance of pluripotent stem cells. 2. The method of claim 1 , wherein Ris an amino group (NH); Ris hydrogen; and the portion indicated by - - - is a double bond.3. The method of claim 1 , wherein Ris a dimethylamino group (N(CH)); Ris a hydroxyl group (OH); and the portion indicated by - - - is a double bond.4. The method of claim 1 , wherein the compound of formula 1 is selected from the group consisting of the following compounds:1) 3-[3-(1H-indol-3-yl)acrylamido]benzamide; and2) 3-[3-(1H-indol-3-yl)acrylamido]-4-hydroxy-N,N-dimethylbenzamide.5. The method of claim 1 , wherein the pluripotent stem cells are embryonic stem cells or induced pluripotent stem cells.6. The method of claim 1 , wherein the pluripotent stem cells are of human origin.7. The method of claim 1 , wherein the concentration of the compound of formula 1 or a pharmaceutically acceptable salt thereof is 0.01-20 μM.8. The method of claim 1 , culturing pluripotent stem cells in an undifferentiated state corresponds to an increase in Oct4 and H3K9ace level compared to those in a control group not cultured in the composition. This application is a division of U.S. patent application Ser. No. 14/358,672, filed May 15, 2014, which is a 35 U.S.C. §371 filing of International Patent Application No. PCT/KR2012/009420, filed Nov. 8, 2012, which claims priority to Korean Patent Application No. 10-2012-0056881, filed May 29, 2012, and Korean Patent Application No. 10-2012-0057803, filed May 30, 2012, the entire disclosures of which are hereby incorporated herein by reference.The present invention relates to an indoleacrylic acid-based novel compound of formula 1, a cell culture medium ...

PHENYL-UREA AND PHENYL-CARBAMATE DERIVATIVES AS INHIBITORS OF PROTEIN AGGREGATION

The present invention relates to certain phenyl-urea and phenyl-carbamate derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, and multiple system atrophy. 2. The compound of claim 1 , wherein Het is an 8-membered bicyclic heteroaryl with at least one nitrogen ring atom.3. The compound of claim 1 , wherein Het is 1H-indolyl claim 1 , 1H-benzimidazolyl claim 1 , 5H-pyrrolo[2 claim 1 ,3-b]pyrazinyl claim 1 , or 1H-imidazo[4 claim 1 ,5-b]pyrazinyl.4. The compound of claim 1 , wherein X is —CH— claim 1 , —CHCH— claim 1 , —CHO— claim 1 , or —CHNH—.5. The compound of claim 1 , wherein X is —CH— claim 1 , —CHCH— claim 1 , or —CHO—.6. The compound of claim 1 , wherein W is O and Y is NH.7. The compound of claim 1 , wherein W is NH and Y is O.8. The compound of claim 1 , wherein X and Y are both NH.9. The compound of claim 1 , wherein Z is O.10. The compound of claim 1 , wherein Ris amino claim 1 , methylamino claim 1 , dimethylamino claim 1 , or guanidino claim 1 , or is a pyrrolyl claim 1 , imidazolyl claim 1 , pyrazolyl claim 1 , pyridinyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , pyridazinyl claim 1 , oxazolyl claim 1 , thiazolyl claim 1 , isoxazolyl claim 1 , isothiazolyl claim 1 , triazolyl claim 1 , or tetrazolyl claim 1 , each unsubstituted or substituted with one or two Rsubstituents; or a pyrrolidinyl claim 1 , piperidinyl claim 1 , piperazinyl claim 1 , azepanyl claim 1 , morpholinyl claim 1 , thiomorpholinyl claim 1 , oxo-thiomorpholinyl claim 1 , or dioxo-thiomorpholinyl claim 1 , each unsubstituted or substituted with one or two Rsubstituents.11. The compound of claim 1 , wherein Ris amino or guanidino; or a pyrrolyl claim 1 , imidazolyl claim 1 , ...

Halogenated compounds for photodynamic therapy

Halo-organic heterocyclic compounds are described, in which at least two halogen atoms are bound to a nitrogen-containing heterocyclic terminal moiety of the compound, with at least one of such halogen atoms being iodine or bromine. Also described are polymethine dyes based on these heterocyclic compounds, and dendrimeric compounds and conjugates of such polymethine dyes. The polymethine dyes are characterized by enhanced properties, e.g., brightness, photostability, sensitivity and/or selective affinity that make them useful to target cancer cells, pathogenic microorganisms, and/or other biological materials, in applications such as photodynamic therapy, photodynamic antimicrobial chemotherapy (PACT), cancer treatment, selective removal or attachment of biological materials, antimicrobial coating materials, and other diagnostic, theranostic, spectrum shifting, deposition/growth, and analytic applications.

MIF MODULATORS

The invention provides novel heterocyclic compounds, pharmaceutical compositions and methods of treatment that modulate levels of MIF expression and treat disorders associated with high or low levels of MIF expression. 2. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , stereoisomer claim 1 , solvate or polymorph thereof claim 1 , wherein:{'sup': 6', 'A1', 'B1, 'sub': 2', 'j', '2', 'm', '2', 'm, '(1) Ris an optionally substituted (CH)-phenyl group, or an optionally substituted (CH)-heterocyclic group or a (CH)-heteroaryl) group; and Rand Rform an optionally substituted phenyl or pyridyl group, or'}{'sup': 6', 'B1', 'A1, 'sub': 2', 'j', '2', 'm', '2', 'j', '2', 'm, '(2) Ris an optionally substituted (CH)-phenyl group, an optionally substituted (CH)-heterocyclic group, or an optionally substituted carbonyl phenyl or an optionally substituted carbonyl heteroaryl group, Ris H, and Ris an optionally substituted (CH)-phenyl group, an optionally substituted (CH)-heterocyclic group, an optionally substituted carbonyl phenyl or an optionally substituted carbonyl heteroaryl group.'}4. The compound of claim 3 , or a pharmaceutically acceptable salt claim 3 , stereoisomer claim 3 , solvate or polymorph thereof claim 3 , wherein R is an optionally substituted (CH)-phenyl group claim 3 , an optionally substituted (CH)-heteroaryl group claim 3 , an optionally substituted carbonyl phenyl or an optionally substituted carbonyl heteroaryl group.742-. (canceled)44. The compound of claim 43 , or a pharmaceutically acceptable salt claim 43 , stereoisomer claim 43 , solvate or polymorph thereof claim 43 , wherein:{'sup': XN1', 'XN1', 'YC1', 'YC2', 'YC1', 'YC2', 'YC1', 'YC1, 'sub': 2', '2', 'm, '(1) X is N—R, Ris absent, Y is CRR, Ris absent, Ris an optionally substituted (CH)j-phenyl group, an optionally substituted (CH)-heterocyclic group, an optionally substituted carbonyl phenyl group, an optionally substituted carbonyl heteroaryl group, or Rtogether with ...

PROTECTING GROUP FOR INDOLE GROUP, NUCLEIC ACID-SYNTHESIZING AMIDITE AND NUCLEIC ACID-SYNTHESIZING METHOD

A protecting group for 1-nitrogen atom of an indole group including a sulfonylethyl carbamate group, wherein the protecting group is represented by the following General Formula (I) and capable of being removed from the 1-nitrogen atom of the indole group in an aprotic solvent:

CYANINE COMPOUNDS

Compounds used as labels with properties comparable to known fluorescent compounds. The compounds can be conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided. 5. A method of labeling at least one biomolecule claim 2 , the method comprising providing a composition comprising at least one excipient and the compound of in an effective concentration to label at least one biomolecule under conditions sufficient for labeling the biomolecule with the compound.6. The method of wherein the biomolecule is selected from the group consisting of a protein claim 5 , antibody claim 5 , enzyme claim 5 , nucleoside triphosphate claim 5 , oligonucleotide claim 5 , biotin claim 5 , hapten claim 5 , cofactor claim 5 , lectin claim 5 , antibody binding protein claim 5 , carotenoid claim 5 , carbohydrate claim 5 , hormone claim 5 , neurotransmitter claim 5 , growth factors claim 5 , toxin claim 5 , biological cell claim 5 , lipid claim 5 , receptor binding drug claim 5 , fluorescent proteins claim 5 , organic polymer carrier material claim 5 , inorganic carrier material claim 5 , and combinations thereof.7. A method of labeling at least one biomolecule claim 3 , the method comprising providing a composition comprising at least one excipient and the compound of in an effective concentration to label at least one biomolecule under conditions sufficient for labeling the biomolecule with the compound.8. The method of wherein the biomolecule is selected from the group consisting of a protein claim 7 , antibody claim 7 , enzyme claim 7 , nucleoside triphosphate claim 7 , oligonucleotide claim 7 , biotin claim 7 , hapten claim 7 , cofactor claim 7 , lectin claim 7 , antibody binding protein claim 7 , carotenoid claim 7 , carbohydrate claim 7 , hormone claim 7 , neurotransmitter claim 7 , growth factors claim 7 , toxin claim 7 , biological ...

PRIMARY CARBOXAMIDES AS BTK INHIBITORS

The invention provides compounds of Formula (I) 2. The compound according to claim 1 , wherein Y is CRand Rof Y is H claim 1 , optionally substituted ethenyl claim 1 , optionally substituted ethyl claim 1 , optionally substituted methyl claim 1 , optionally substituted 2 claim 1 ,3-dihydrobenzofuranyl claim 1 , optionally substituted 1 claim 1 ,4-dioxanyl claim 1 , optionally substituted 3 claim 1 ,4-dihydro-2H-benzo[b][1 claim 1 ,4]oxazinyl claim 1 , optionally substituted 6 claim 1 ,7-dihydro-4H-pyrazolo[5 claim 1 ,1-c][1 claim 1 ,4]oxazinyl claim 1 , optionally substituted chromanyl claim 1 , optionally substituted cyclohexenyl claim 1 , optionally substituted cyclopropyl claim 1 , optionally substituted tetrahydrofuranyl claim 1 , optionally substituted isochromanyl claim 1 , optionally substituted 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-isoquinolinyl claim 1 , optionally substituted isoxazolyl claim 1 , optionally substituted morpholinyl claim 1 , optionally substituted oxetanyl claim 1 , optionally substituted phenyl claim 1 , optionally substituted piperidinyl claim 1 , optionally substituted piperazinyl claim 1 , optionally substituted 3 claim 1 ,6-dihydro-2H-pyranyl claim 1 , optionally substituted pyrano[4 claim 1 ,3-b]pyridinyl claim 1 , optionally substituted pyrazolyl claim 1 , optionally substituted pyridinyl claim 1 , optionally substituted 3H-pyridin-1-one claim 1 , optionally substituted 1 claim 1 ,2 claim 1 ,3 claim 1 ,6-tetrahydropyridinyl claim 1 , optionally substituted pyrimidinyl claim 1 , optionally substituted pyrrolidinyl claim 1 , optionally substituted 2 claim 1 ,5-dihydropyrrolyl claim 1 , optionally substituted tetrahydropyranyl or optionally substituted tetrahydro-2H-thiopyranyl.3. The compound according to wherein Ris H or Ris optionally substituted by one or more substituents independently selected from the group consisting of CN claim 2 , OH claim 2 , ═O claim 2 , halogen claim 2 , (C-C)alkyl claim 2 , (C-C)alkoxy claim 2 , — ...

NEW DERIVATIVES OF INDOLE FOR THE TREATMENT OF CANCER, VIRAL INFECTIONS AND LUNG DISEASES

The present invention relates to a new class of indole derivatives, having a particular MKlp2 inhibition profile and useful as a therapeutic agent, in particular for the treatment of cancer, viral infections and lung diseases. 4. The method according to claim 1 , wherein R′ is H.5. The method according to claim 1 , wherein Rrepresents a halogen selected in the group consisting of a bromine and a chlorine.6. The method according to claim 1 , wherein Ris H.7. The method according to claim 1 , wherein R′ is a halogen chosen among a bromine claim 1 , a chlorine claim 1 , or a fluorine.8. The method according to claim 1 , wherein Rrepresents:{'sub': 1', '6, 'a radical (C-C)alkoxy, or phenoxy, said radicals being optionally substituted by at least one halogen;'}a halogen;{'sub': 4', '5', '1', '6', '4', '5', '4', '5', '1', '6', '4', '5, 'a R—N—Runit or a S—(C-C)alkyl-NRRunit, wherein Rand Rrepresent H or a (C-C)alkyl group, with the proviso that at least one among Rand Ris not H,'}{'sub': 6', '6', '1', '6, 'a NHCORunit wherein Rrepresents (C-C)alkyl group,'}{'sub': 1', '6', '1', '6', '1', '6, 'a radical thio-(C-C)alkyl, thio-aryl, thio-heteroaryl, thio-(C-C)alkyl-aryl, said radicals being optionally substituted by at least one halogen or by a (C-C)alkoxy group;'}an aryl group optionally substituted by at least one halogen, or a trifluoromethyl group; ora heteroaryl group.9. The method according to claim 1 , wherein Rrepresents:{'sub': 1', '6, 'a radical (C-C)alkoxy selected from the group consisting of a methoxy group, an ethoxy group, and an isopropoxy group, or a phenoxy group, optionally substituted by a fluorine;'}a halogen selected from the group consisting of a fluorine and a chlorine,{'sub': 4', '5', '1', '6', '4', '5', '4', '5, 'a R—N—Runit or a S—(C-C)alkyl-NRRunit wherein Rand Rrepresent a methyl or an ethyl group{'sub': 6', '6, 'a NHCORunit wherein Rrepresents a tert-butyl group;'}a radical selected in the group consisting of a thio-methyl group, a thio-ethyl ...

INDOLE CARBOXAMIDE COMPOUNDS

Disclosed are compounds of Formula (I): 117-. (canceled)19. The compound according to wherein:{'sub': 1', '3, 'Ris H or —CH;'}{'sub': 2', '3, 'Ris H or —CH;'}{'sub': '3', 'Ris F or Cl; and'}{'sub': '4', 'Ris H or F.'}20. The compound according to wherein{'sub': '3', 'Ris F.'}24. The compound according to wherein:{'sub': 1', '3, 'Ris —CH;'}{'sub': 2', '3, 'Ris —CH;'}{'sub': '3', 'Ris H or F;'}{'sub': '4', 'Ris H; and'}{'sub': 7', '3, 'each Ris H or —CH.'}25. The compound according to wherein:{'sub': 2', '2', '2', '3', '2', '3', '2', '2, 'Qis —CN, —C(O)CH═CH, —C(O)CH═CHCHN(CH), —C(O)C≡CH, —C(O)C≡C(CH), or —S(O)CH═CH.'}29. The compound according to wherein said compound is:4-((1-acryloylpiperidin-4-yl)amino)-2,3-dimethyl-1H-indole-7-carboxamide (79);4-((1-acryloylpyrrolidin-3-yl)amino)-2,3-dimethyl-1H-indole-7-carboxamide (86);(R)-4-((1-acryloylpyrrolidin-3-yl)amino)-2,3-dimethyl-1H-indole-7-carboxamide (87);(S)-4-((1-acryloylpyrrolidin-3-yl)amino)-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide (88);4-((1-acryloylpiperidin-3-yl)amino)-2,3-dimethyl-1H-indole-7-carboxamide (91);4-((1-acryloylpiperidin-4-yl)amino)-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide (92);(S)-4-((1-acryloylpyrrolidin-3-yl)(methyl)amino)-2,3-dimethyl-1H-indole-7-carboxamide (94);(S)-4-((1-acryloylpyrrolidin-3-yl)(methyl)amino)-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide (96);(RS)-2,3-dimethyl-4-((1-propioloylpyrrolidin-3-yl)amino)-1H-indole-7-carboxamide (103);2,3-dimethyl-4-((1-propioloylpiperidin-3-yl)amino)-1H-indole-7-carboxamide (106);4-((1-(but-2-ynoyl)piperidin-4-yl)amino)-2,3-dim ethyl-1H-indole-7-carboxamide (107);2,3-dimethyl-4-((1-propioloylpiperidin-4-yl)amino)-1H-indole-7-carboxamide (114);4-((1-(but-2-ynoyl)pyrrolidin-3-yl)amino)-2,3-dimethyl-1H-indole-7-carboxamide (121);4-((1-(but-2-ynoyl)piperidin-4-yl)amino)-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide (122);(S,E)-4-((1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)amino)-2,3-dimethyl-1H-indole-7-carboxamide (124);2,3-dimethyl- ...

PRODRUGS OF GLUTAMINE ANALOGS

The disclosure provides compounds having formula (I): 2. (canceled)3. (canceled)4. The compound of claim 1 , wherein Ris selected from the group consisting of methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , trimethylammonium claim 1 , triethylammonium claim 1 , tri(hydroxyethyl)ammonium claim 1 , tripropylammonium claim 1 , and tri(hydroxypropyl)ammonium.5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)18. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier claim 1 , diluent claim 1 , or excipient.19. A method of treating cancer in a subject claim 1 , the method comprising administering to the subject in need thereof a compound of claim 1 , or a pharmaceutically acceptable salt thereof.20. A method of treating cancer in a subject claim 17 , the method comprising administering to the subject in need thereof a compound of claim 17 , or a pharmaceutically acceptable salt thereof.21. The method of claim 20 , wherein the cancer is hepatocellular cancer claim 20 , brain cancer claim 20 , lung cancer claim 20 , breast cancer claim 20 , head and neck cancer claim 20 , pancreatic cancer claim 20 , prostate cancer claim 20 , melanoma claim 20 , colorectal cancer claim 20 , acute lymphoblastic leukemia claim 20 , acute myelogenous leukemia claim 20 , or chronic myelocytic leukemia.22. The method of claim 21 , wherein the cancer is colon cancer.23. The method of claim 21 , wherein the cancer is breast cancer.24. The method of claim 21 , wherein the cancer is brain cancer.25. The method of claim 21 , wherein the cancer is pancreatic cancer.26. The method of claim 21 , wherein the cancer is prostate cancer.27. The method of claim 20 , wherein the cancer is a solid tumor.28. The compound of claim 1 , wherein{'sub': '3', 'Ris H; and'}{'sub': '4', 'Ris methyl, iPr, or aryl.'}29. The compound of claim 1 , wherein{'sub': ...

Atropisomers and Methods of Altering Enantiomeric Excess

Provided herein are methods of altering enantiomeric excess. The methods may include irradiating an atropisomer that includes at least one chiral substituent to alter the enantiomeric excess of the atropisomer. The at least one chiral substituent may be removed following irradiation. 1. A method of altering enantiomeric excess , the method comprising:providing an atropisomer having an enantiomeric excess of 0% to 100%, wherein the atropisomer comprises at least one chiral substituent; andirradiating the atropisomer to alter the enantiomeric excess.3. The method of claim 2 , wherein Ris a C-Chydrocarbyl comprising at least one chiral atom.4. The method of claim 2 , wherein Ris an N-protected amino acid substituent.9. The method of claim 1 , wherein the enantiomeric excess is 0% to about 5% prior to the irradiating of the atropisomer claim 1 , and the atropisomer is a racemic atropisomer.10. The method of claim 1 , wherein the enantiomeric excess is about 95% to 100% prior to the irradiating of the atropisomer claim 1 , and the atropisomer is an enantiopure atropisomer.11. The method of claim 1 , wherein the providing of the atropisomer comprises:contacting an unsubstituted atropisomer with a chiral substituent precursor to form the atropisomer,wherein the unsubstituted atropisomer comprises a hydroxyl functional group, and the chiral substituent precursor comprises an ester functional group or an acyl halide functional group.12. The method of claim 11 , wherein the chiral substituent precursor comprises an N-protected amino acid.16. The method of claim 1 , wherein the irradiating of the atropisomer comprises exposing the atropisomer to electromagnetic radiation comprising one or more wavelengths of about 10 nm to about 900 nm.17. The method of claim 1 , wherein the atropisomer is contacted with a base during at least a portion of the irradiating of the atropisomer.19. The atropisomer of claim 18 , wherein Ris an N-protected amino acid substituent. This application ...

Five-Membered-Fused-Six-Membered Aza-Aromatic Ring Compound, Preparation Method Thereof, Pharmaceutical Composition And Application Thereof

The invention relates to the field of medicinal chemistry, and to five-membered-fused-six-membered aza-aromatic ring compound, preparation method thereof, pharmaceutical composition and application thereof. In particular, the invention relates to a type of compounds capable of specifically enhancing ubiquitination degradation of Ras proteins, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with Ras activity in vivo, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis. 13. A pharmaceutical composition comprising the compound according to any one of - or a stereoisomer thereof , a prodrug thereof , a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof and and optionally a pharmaceutically acceptable excipient. The invention relates to the field of medicinal chemistry, and in particular to a type of compounds capable of specifically enhancing ubiquitination degradation of Ras proteins, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with Ras activity in vivo, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis.Ras protein, as a molecular switch in cells, plays a key role in numerous physiological and biochemical regulation processes in cells, including gene expression, cell growth and differentiation, cell cycle, cytoskeleton and cell migration, membrane vesicle transport, transport between nucleus and cytoplasm and the like. Meanwhile, Ras proteins (including H-Ras, K-Ras and N-Ras) are also the most common protooncoproteins in humans, closely related to tumor growth and transformation activity. RAS gene mutations are found in 20%-30% ...

N-AROMATIC AMIDE COMPUNDS, PREPARATION METHODS AND USES THEREOF

The present invention relates to N-aromatic amide compounds with formula (I) and/or (II) and preparation methods therefor, pharmaceutical compositions and pharmaceutical formulations containing the compounds with formula (I) and/or (II), and use of the compounds with formula (I) and/or (II) in preparing a medicament for the treatment of diseases related to androgens. The definitions of R, R, R, R, R, R, W, W, W, Wand Win the formula are the same as those in the description. The compounds with the formula (I) and/or (II) are capable of binding to the androgen receptors and have activity for anti-androgen and degrading androgen receptor. The compounds can be used alone or as compositions for the treatment of various androgen-related diseases such as prostate cancer, prostate hyperplasia, breast cancer, bladder cancer, ovarian cancer and the like, and also for the treatment of acne, hirsutism, psilosis and other diseases. 4. The N-aromatic amide compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein an optical isomer of the compound is a racemic claim 1 , levorotatory and/or dextrorotatory isomer.6. A pharmaceutical composition claim 1 , comprising the N-aromatic amide compound or the pharmaceutically acceptable salt thereof according to .8. The method according to claim 7 , wherein the androgen-related disease is prostate cancer claim 7 , prostate hyperplasia claim 7 , breast cancer claim 7 , bladder cancer claim 7 , ovarian cancer claim 7 , acne claim 7 , hirsutism or psilosis.9. The method according to claim 7 , wherein the mammal is a human. The present invention relates to an N-aromatic amide compound, having effects of anti-androgen and degrading androgen receptors, a preparation method thereof, and a pharmaceutical use thereof. The compound can be used for treating diseases related to androgens such as prostate cancer, prostate hyperplasia, breast cancer, bladder cancer, acne, hirsutism, psilosis or the like.Androgen receptors, ...

NOVEL COMPOUNDS AND COMPOSITIONS FOR INHIBITION OF FASN

The present invention relates to compounds and composition for inhibition of FASN, their synthesis, applications, and antidotes. An illustrative compound of the invention is shown below: 6. The compound of claim 2 , wherein A and B are O.10. The compound of claim 2 , wherein Aris a substituted or unsubstituted 5-6 membered monocyclic aryl or heteroaryl.11. The compound of claim 10 , wherein Aris a substituted or unsubstituted 5 membered monocyclic aryl or heteroaryl and said heteroaryl has 1 or 2 heteroatoms which are independently S or N.13. The compound of claim 10 , wherein Aris a substituted or unsubstituted 6 membered monocyclic aryl or heteroaryl and said heteroaryl has 1 or 2 heteroatoms which are N.18. The compound of claim 2 , wherein Aris a substituted or unsubstituted 9 membered 6 claim 2 ,5-bicyclic heteroaryl and said heteroaryl has 1 claim 2 , 2 claim 2 , or 3 heteroatoms which are independently O claim 2 , S or N.20. The compound of claim 2 , wherein Ris a substituted or unsubstituted monocyclic or bicyclic 5-10 membered aryl or heteroaryl.21. The compound of claim 20 , wherein Ris a substituted or unsubstituted monocyclic 6 membered aryl.23. The compound of claim 20 , wherein Ris a substituted or unsubstituted bicyclic 8-10 membered aryl or 8-10 membered heteroaryl.24. The compound of claim 23 , wherein Ris a substituted or unsubstituted 8 membered 5 claim 23 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 23 , 2 claim 23 , 3 claim 23 , or 4 heteroatoms and said heteroatoms are independently O claim 23 , S claim 23 , or N.26. The compound of claim 20 , wherein Ris a substituted or unsubstituted 9 membered 6 claim 20 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 20 , 2 claim 20 , 3 claim 20 , or 4 heteroatoms and said heteroatoms are independently O claim 20 , S claim 20 , or N.28. The compound of claim 20 , wherein Ris a substituted or unsubstituted 10 membered 6 claim 20 ,6 bicyclic aryl or heteroaryl and said heteroaryl has 1 claim ...

CRYSTALLINE POLYMORPHIC FORMS OF AN ANTIDIABETIC COMPOUND

The present invention relates to polymorphic forms of a compound of formula A: 2. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with in the form of a free acid hydrate of polymorphic Form I.5. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with in the form of a free acid hydrate having at least three C13 solid state NMR characteristic signals with chemical shift values selected from the group consisting of: 11.3 claim 1 , 20.2 claim 1 , 23.9 claim 1 , 33.1 claim 1 , 45.5 claim 1 , 108.6 claim 1 , 118.7 claim 1 , 131.7 claim 1 , 139.3 claim 1 , 148.5 claim 1 , 170.1 and 179.9 ppm.6. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with in the form of an anhydrous free acid.9. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with in the form of an anhydrous free acid having a 19F solid state NMR as shown in .10. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with in the form of a free acid hydrate/methanolate solvate.1118-. (canceled)19. A pharmaceutical composition comprised of a polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with in combination with a pharmaceutically acceptable carrier.2023-. (canceled) The present invention relates to novel polymorphic forms of a compound of formula A. This compound is useful as a pharmaceutically active ingredient for the treatment of type 2 diabetes and related conditions, such as hyperglycemia, obesity, dyslipidemia, and the metabolic syndrome.Type 2 diabetes remains a serious medical problem. There is an ongoing need for new treatments that are more effective and that have fewer side effects. Glucagon receptor antagonists are important upcoming medications for the treatment of type 2 diabetes and the present compound is particularly useful in this regard.The ...

GLUCAGON RECEPTOR ANTAGONISTS

Provided herein are compounds, including enantiomerically pure forms thereof, and pharmaceutically acceptable salts or co-crystals and prodrugs thereof which have glucagon receptor antagonist or inverse agonist activity. Further, provided herein are pharmaceutical compositions and methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucagon receptor antagonist is indicated, including Type I and II diabetes, insulin resistance and hyperglycemia. 3. The compound of claim 1 , wherein:{'sup': '2', 'sub': '3', 'Ris H or Cl or CH;'}{'sup': '3', 'sub': 3', '2', '3', '2', '2', '3', '2', '2', '3, 'Ris selected from a group of hydrogen, CH, CHCH, CHCHCH, and CHCHCF; X is CH;'}{'sup': 3', '3', '3', '3', '1', '3', '3', '3', '3', '3', '3', '3', '3', '3, 'sub': '2', 'L is —OCHR—, —SCHR—, —NRCHR—, —CHRCHR—, —CHRO—, —CHRS—, —CHRNR—, -heteroarylCHR—, -heteroarylO—, —OCHCHR—, —NHCHRaryl-, and —OCHRaryl-, where the aryl and the heteroaryl are independently optionally substituted.'}4. The compound of claim 3 , wherein L is —OCHR— claim 3 , —CHRCHR— claim 3 , and -heteroarylCHR— claim 3 , where the heteroaryl is substituted with an aryl optionally substituted with F claim 3 , Cl claim 3 , CH claim 3 , OCH claim 3 , and CF.6. A pharmaceutical composition comprising a compound according to claim 1 , and one or more pharmaceutically acceptable excipients or carriers.7. The pharmaceutical composition of claim 6 , further comprising a second therapeutic agent.8. The pharmaceutical composition of claim 7 , wherein the second therapeutic agent is an antidiabetic agent.9. The pharmaceutical composition of claim 7 , wherein the second therapeutic agent is at least one selected from the group consisting of: insulin sensitizers claim 7 , biguanides claim 7 , metformin claim 7 , PPAR agonists claim 7 , triglitazone claim 7 , pioglitazone claim 7 , rosiglitazone claim 7 , insulin and ...

HALOGENATED COMPOUNDS FOR PHOTODYNAMIC THERAPY

Halo-organic heterocyclic compounds are described, in which at least two halogen atoms are bound to a nitrogen-containing heterocyclic terminal moiety of the compound, with at least one of such halogen atoms being iodine or bromine. Also described are polymethine dyes based on these heterocyclic compounds, and dendrimeric compounds and conjugates of such polymethine dyes. The polymethine dyes are characterized by enhanced properties, e.g., brightness, photostability, sensitivity and/or selective affinity that make them useful to target cancer cells, pathogenic microorganisms, and/or other biological materials, in applications such as photodynamic therapy, photodynamic antimicrobial chemotherapy (PACT), cancer treatment, selective removal or attachment of biological materials, antimicrobial coating materials, and other diagnostic, theranostic, spectrum shifting, deposition/growth, and analytic applications. 2. The method of claim 1 , wherein at least two halo substituents in ring A are iodine.3. The method of claim 1 , wherein at least two halo substituents in ring A are bromine.4. The method of claim 1 , wherein each of X claim 1 , X claim 1 , X claim 1 , and Xis C—R.5. The method of claim 1 , wherein Y is C(R)(R).6. The method of claim 1 , wherein Sis a moiety that is conjugated to ring A through linker claim 1 , L claim 1 , and is selected from the group consisting of alkanes claim 1 , alkenes claim 1 , alkynes claim 1 , polyethers claim 1 , polyamines claim 1 , cycloparaffins claim 1 , cycloolefins claim 1 , cyclynes claim 1 , heteroalicyclic groups claim 1 , aromatic groups claim 1 , heteroaromatic groups claim 1 , organic dyes claim 1 , polymethines claim 1 , dendrimers claim 1 , nanoparticles claim 1 , biological molecules claim 1 , and biological compounds claim 1 , and wherein the alkanes claim 1 , alkenes claim 1 , alkynes claim 1 , polyethers claim 1 , polyamines claim 1 , cycloparaffins claim 1 , cycloolefins claim 1 , cyclynes claim 1 , heteroalicyclic ...

MODIFIED CARBOCYANINE DYES AND THEIR CONJUGATES

Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens. 2. The compound of claim 1 , wherein Y represents the atoms necessary to form two fused aromatic rings.3. The compound of claim 1 , wherein the atoms of Y are selected from —CH and —C.4. The compound of claim 1 , wherein X is —CRR.5. The compound of claim 4 , wherein Ris C-Calkyl.6. The compound of claim 4 , wherein Ris methyl.7. The compound of claim 1 , wherein α is 1.8. The compound of claim 1 , wherein Ris C-Calkyl.9. The compound of claim 8 , wherein Ris methyl or ethyl.10. The compound of claim 1 , wherein W represents the atoms necessary to form two fused aromatic rings.11. The compound of claim 1 , wherein the atoms of W are selected from —CH and —C.12. The compound of claim 1 , wherein Z is —CRR.13. The compound of claim 12 , wherein each of Rand Ris methyl.14. The compound of claim 1 , wherein δ is 1.15. The compound of claim 1 , wherein Ris methyl or ethyl.16. The compound of claim 1 , wherein a is 1 and b is 0.17. The compound of claim 1 , wherein Ris a phosphoramidite.21. The compound of claim 1 , wherein L comprises ether bonds.22. The compound of claim 1 , wherein L contains 4-10 nonhydrogen atoms claim 1 , including one or two heteroatoms.23. The compound of claim 1 , wherein L contains 1-6 carbon atoms. This application is a divisional of U.S. Ser. No. 14/656,992, filed Mar. 14, 2015, which is a continuation of co-pending U.S. Ser. No. 14/030,835, filed Sep. 18, 2013 to issue as U.S. Pat. No. 9,018,396 on Apr. 28, 2015, which is a continuation of U.S. Ser. No. 13/556,643, filed Jul. 24, 2012 ( ...

PLANT GROWTH REGULATOR

Providing an auxin derivative that can exert its intended effect more efficiently, while reducing any unintended effects. 3. The growth regulator described in claim 1 , wherein Ris a hydrogen atom claim 1 , and Ris a carboxyalkyl group.4. The growth regulator described in claim 1 , wherein Ris an adamantyl group which may be substituted claim 1 , an aryl group which may be substituted claim 1 , or an alkyl group which may be substituted.6. The growth regulator described in claim 1 , wherein the previously mentioned aryl group is a phenyl group claim 1 , a phenylalkyl group claim 1 , or a naphthyl group.7. The growth regulator described in claim 1 , wherein the previously mentioned alkyl group has 4 to 20 carbon atoms.8. The growth regulator described in claim 1 , wherein the previously mentioned adamantyl group claim 1 , aryl group claim 1 , alkyl group claim 1 , and the heterocyclic group are substituted by at least one substituent selected from the group consisting of an alkyl group claim 1 , an alkoxy group claim 1 , a halogen atom claim 1 , an aryl group claim 1 , and an aryloxy group.10. The growth regulator described in claim 1 , wherein the previously mentioned reduced auxin-sensitivity auxin receptor TIR1 is an auxin receptor TIR1 resulting from the replacement of the amino acid residue that interacts with the benzene ring in the auxin indole ring with another amino acid residue.11. The growth regulator described in claim 10 , wherein the other amino acid mentioned previously is glycine.14. A reduced auxin-sensitivity auxin receptor TIR1 resulting from the replacement of the amino acid residue in the auxin receptor TIR1 that interacts with the benzene ring in the auxin indole ring with another amino acid residue.16. A reduced auxin-sensitivity auxin receptor TIR1 as described in claim 14 , wherein the other amino acid residue mentioned previously is alanine claim 14 , serine or glycine.17. A polynucleotide encoding the reduced auxin-sensitivity auxin ...

Vinyl autotaxin inhibitor compounds

Described herein are compounds that are autotaxin inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with autotaxin activity.

INDOLINYL SULFONAMIDE AND RELATED COMPOUNDS FOR USE AS AGONISTS OF RORY AND THE TREATMENT OF DISEASE

The invention provides aryl indolinyl sulfonamide and related compounds, pharmaceutical compositions, methods of promoting RORγ activity and/or increasing the amount of IL-17 in a subject, and therapeutic uses of the indolinyl sulfonamide and related compounds, such as treating medical conditions in which activation of immune response is beneficial. 2. The compound of claim 1 , wherein Ais phenylene or 5-6 membered heteroarylene.3. The compound of claim 1 , wherein Y is —C(R)—C(R)(R)—ψ or —C(R)(R)—C(R)-ψ.4. (canceled)6. (canceled)8. (canceled)1017-. (canceled)18. The compound of claim 1 , wherein Ris —(Calkylene)-A.19. The compound of claim 9 , wherein Ris —(Calkylene)-A.2021-. (canceled)22. The compound of claim 19 , wherein Ais —COR.2336-. (canceled)37. The compound of claim 1 , wherein X is phenyl substituted by 1 claim 1 , 2 claim 1 , or 3 substituents independently selected from the group consisting of halogen claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , and Chaloalkoxy.3842-. (canceled)44. (canceled)45. (canceled)4785-. (canceled)86. A compound in Table 10 herein or a pharmaceutically acceptable salt thereof.87. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.88. A method of treating a disorder selected from the group consisting of cancer claim 1 , bacterial infection claim 1 , fungal infection claim 1 , and immune deficiency disorder claim 1 , comprising administering a therapeutically effective amount of a compound of to a subject in need thereof to treat the disorder.89. The method of claim 88 , wherein the disorder is cancer.90. The method of claim 88 , wherein the disorder is colon cancer claim 88 , pancreatic cancer claim 88 , breast cancer claim 88 , ovarian cancer claim 88 , prostate cancer claim 88 , squamous cell carcinoma claim 88 , basal cell carcinoma claim 88 , adenocarcinoma claim 88 , sweat gland carcinoma claim 88 , sebaceous gland carcinoma claim 88 , lung cancer claim 88 , leukemia claim 88 ...

Tlr-independent small molecule adjuvants

A TLR-independent adjuvant compound that corresponds in structure to Formula I, below, or its pharmaceutically acceptable salt is disclosed in which X, Y, Z, n, R 1 , R 2 , R 3 , R 4 and W are defined within. Also disclosed are a method of its preparation and use, as well as a pharmaceutical composition containing the same.

NOVEL 3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE

A compound of Formula I is provided: 2. The compound according to claim 1 , wherein Q is H.3. The compound according to claim 1 , wherein X1 and X2 are independently H claim 1 , F or Cl.4. The compound according to claim 3 , wherein X1 is H and X2 is F.5. The compound according to claim 1 , wherein A2 is H.6. The compound according to claim 1 , wherein A1 is SO2NR5R6.7. The compound according to claim 6 , wherein R5 and/or R6 claim 6 , the heterocycle is an optionally substituted 4 claim 6 , 5 or 6-membered heterocycle ring claim 6 , or NR5R6 together form a heterocycle ring of 4 claim 6 , 5 or 6 members having 1 claim 6 , 2 or 3 heteroatoms claim 6 , said heterocycle being optionally substituted with 1 claim 6 , 2 or 3 substituents independently selected from C1 to C6 alkyl claim 6 , OH claim 6 , halogen claim 6 , amino claim 6 , SO2 claim 6 , or oxo.8. The compound according to claim 7 , wherein when the 1 claim 7 , 2 claim 7 , or 3 heteroatom of the 4 claim 7 , 5 or 6-membered heterocycle ring comprise at least one N atom.9. The compound according to claim 6 , wherein in SO2NR5CR9 claim 6 , R9 is a C1-C4 alkyl which is optionally substituted with OH or halogen.10. The compound according to claim 1 , wherein the compound is in salt form.11. The compound according to claim 1 , wherein the compound is not in salt form.12. The compound according to claim 1 , wherein the compound is selected from the group consisting of:6-Fluoro-3-(4-methanesulfonyl-phenyl)-1H-indole,N-(2-aminoethyl)-4-(6-fluoro-1H-indol-3-yl)benzamide,(4-(6-fluoro-1H-indol-3-yl)phenyl)(piperazin-1-yl)methanone,6-fluoro-3-(4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole,4-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)morpholine,4-(6-fluoro-1H-indol-3-yl)benzenesulfonamide,6-fluoro-3-(3-(piperazin-1-ylsulfonyl)phenyl)-1H-indole,N-(2-aminoethyl)-4-(6-fluoro-1H-indol-3-yl)benzenesulfonamide,N-(2-aminoethyl)-3-(6-fluoro-1H-indol-3-yl)benzenesulfonamide,3-(6-fluoro-1H-indol-3-yl)benzenesulfonamide,3-(4-(((cis)-3 ...

5-OXO-ETE RECEPTOR ANTAGONIST COMPOUNDS

The present invention relates to novel pharmaceutically-useful compounds which are antagonists of the 5-oxo-ETE receptors, such as the OXE receptor. These compounds have use as therapeutic and/or prophylactic agents for diseases characterized by tissue eosinophilia, such as inflammatory conditions including respiratory diseases. The invention also relates to pharmaceutical compositions, to the use of such compounds and compositions as medicaments, and to therapeutic methods. 2. The method of for treating lung claim 1 , pancreatic or prostate cancer.3. The method of for treating atopic dermatitis or acne.4. The method of claim 1 , wherein X claim 1 , X claim 1 , Xand Xis independently selected from the group consisting of H claim 1 , halogen and alkyl group and the remaining of said X claim 1 , X claim 1 , Xor Xare H.5. The method of claim 1 , wherein one of X claim 1 , X claim 1 , Xor Xis selected from the group consisting of H claim 1 , halogen and alkyl group and the remaining of said X claim 1 , X claim 1 , Xor Xare H.6. The method of claim 1 , wherein one of Xor Xis halogen and the remaining of said X claim 1 , X claim 1 , Xor Xare H.7. The method of claim 1 , wherein Ris an alkyl comprising up to 10 carbon atoms claim 1 , provided that when said alkyl is an unsaturated claim 1 , it is comprising 2 or more carbon atoms.8. The method of claim 1 , wherein in i) R1 is (CO)alkyl-COOH claim 1 , said alkyl is optionally substituted with C6-16 aryl or C3-7 cycloalkyl.9. The method of claim 8 , wherein said alkyl portion of said (CO)alkyl-COOH is comprising 2 to 4 carbon atoms.11. The method of claim 1 , wherein in i) claim 1 , Ris Calkyl.12. The method of claim 1 , wherein in ii) R3 is (CO)alkyl-COOH claim 1 , said alkyl is optionally substituted with C6-16 aryl or C3-7 cycloalkyl.13. The method of claim 11 , wherein said alkyl portion of said (CO)alkyl-COOH is comprising 2 to 4 carbon atoms.17. The method of claim 15 , wherein said halogen is Cl.18. The method of ...

NEW DERIVATIVES OF INDOLE FOR THE TREATMENT OF CANCER, VIRAL INFECTIONS AND LUNG DISEASES

The present invention relates to a new class of indole derivatives, having a particular MKlp2 inhibition profile and useful as a therapeutic agent, in particular for the treatment of cancer, viral infections and lung diseases. 4. The compound according to claim 1 , wherein R′ is H.5. The compound according to claim 1 , wherein Rrepresents a halogen selected from the group consisting of a bromine and a chlorine.6. The compound according to claim 1 , wherein Ris H.7. The compound according to claim 1 , wherein R′ is a halogen selected from a bromine claim 1 , a chlorine or a fluorine.8. The compound according to claim 1 , wherein Rrepresents:{'sub': 1', '6, 'a radical (C-C)alkoxy, or phenoxy, said radicals being optionally substituted by at least one halogen;'}a halogen;{'sub': 4', '5', '1', '6', '4', '5', '4', '5', '1', '6', '4', '5, 'a R—N—Runit or a S—(C-C)alkyl-NRRunit, wherein Rand Rrepresent H or a (C-C)alkyl group, with the proviso that at least one among Rand Ris not H;'}{'sub': 6', '6', '1', '6, 'a NHCORunit wherein Rrepresents (C-C)alkyl group;'}{'sub': 1', '6', '1', '6', '1', '6, 'a radical thio-(C-C)alkyl, thio-aryl, thio-heteroaryl, thio-(C-C)alkyl-aryl, said radicals being optionally substituted by at least one halogen or by a (C-C)alkoxy group;'}an aryl group optionally substituted by at least one halogen, or a trifluoromethyl group; ora heteroaryl group.9. The compound according to claim 1 , wherein Rrepresents:{'sub': 1', '6, 'a radical (C-C)alkoxy selected from the group consisting of a methoxy group, an ethoxy group, and an isopropoxy group, or a phenoxy group, optionally substituted by a fluorine, such as a trifluoromethyl;'}a halogen selected from the group consisting of a fluorine and a chlorine;{'sub': 4', '5', '1', '6', '4', '5', '4', '5, 'a R—N—Runit or a S—(C-C)alkyl-NRRunit wherein Rand Rrepresent a methyl or an ethyl group;'}{'sub': 6', '6, 'a NHCORunit wherein Rrepresents a tert-butyl group;'}a radical selected in the group consisting of a ...

Modified carbocyanine dyes and their conjugates

Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens.

N-((3,4,5-TRIMETHOXYSTYRYL)ARYL)CINNAMAMIDE COMPOUNDS AS POTENTIAL ANTICANCER AGENTS AND PROCESS FOR THE PREPARATION THEREOF

The present invention provides a compound of general formula A, useful as potential anticancer agents against human cancer cell lines and process for the preparation thereof. [Formula should be entered here] General formula A where in B selected from aryl, heteroaryl and fused heteroaryl ring R and X selected from H, hydroxy, alkyl, alkoxy, prop-2-ynyloxy, allyloxy, halo, alkylhalides, alkoxy halides, nitro, amine. 3. A compound as claimed in claim 1 , wherein the representative compounds of formula A comprising:N-(2-(3,4,5-Trimethoxystyryl)phenyl)cinnamamide(8a)(E)-3-(2-Methoxyphenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8b)(E)-3-(2-Nitrophenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8d)(E)-3-(2-Aminophenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8e)(E)-3-(3-Methoxyphenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8f)(E)-3-(3-Hydroxyphenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8g)(E)-3-(3-(Prop-2-ynyloxy)phenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8h)(E)-3-(3-(Allyloxy)phenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8i)(E)-3-(3-Nitrophenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8j)(E)-3-(3-Aminophenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8k)(E)-3-(4-Methoxyphenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8l)(E)-3-(4-Hydroxyphenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8m)(E)-3-(4-(Trifluoromethyl)phenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8n)(E)-3-(4-Nitrophenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8o)(E)-3-(4-Aminophenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8p)(E)-3-(4-Chlorophenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8q)(E)-3-(4-Fluorophenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8r)(E)-3-(3,4-Dimethoxyphenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8s)(E)-3-(4-Hydroxy-3-methoxyphenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)acrylamide(8t)(E)-3-(3-Methoxy-4-nitrophenyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl) ...

AMIDE COMPOUND

The present invention relates to compound (I) or a salt thereof which has a RORγt inhibitory action. In the formula (I), each symbol is as defined in the specification. 116.-. (canceled)18. The method of claim 17 , wherein the substituent that Ring A optionally further has is a fluorine atom or a chlorine atom.19. The method of claim 17 , wherein Ris a tert-butyl group claim 17 , a neopentyl group or a trimethylsilyl group.21. The method of claim 17 , wherein Ris a hydrogen atom or a methyl group.22. The method of claim 17 , wherein the compound is (3S)—N-((1R)-2-((4-tert-Butyl-3-fluorophenyl)amino)-1-(4 claim 17 ,4-difluorocyclohexyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide or a salt thereof.23. The method of claim 17 , wherein the compound is N-((1R)-2-((3 claim 17 ,5-Difluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methyl-1 claim 17 ,2-oxazole-5-carboxamide or a salt thereof.24. The method of claim 17 , wherein the compound is (2R)—N-(4-tert-Butyl-3 claim 17 ,5-difluorophenyl)-2-(((3-hydroxy-1 claim 17 ,2-oxazol-5-yl)acetyl)amino)-2-(1-methyl-1H-indazol-5-yl)acetamide or a salt thereof.25. The method of claim 17 , wherein the compound is (3R)—N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide or a salt thereof.26. The method of claim 17 , wherein the compound is selected from the group consisting of(3S)—N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide,N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methyl-1,2-oxazole-5-carboxamide,N-(2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide,(2R)-2-(((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)amino)-N-(3-fluoro-4-(trimethylsilyl)phenyl)-2-(4-(methoxymethyl)phenyl)acetamide,(2R)—N-(3-fluoro-4-(trimethylsilyl)phenyl)-2-(4 ...

Novel compounds and compositions for inhibition of fasn

The present invention relates to compounds and composition for inhibition of FASN, their synthesis, applications, and antidotes. An illustrative compound of the invention is shown below:

NOVEL COMPOUNDS AND COMPOSITIONS FOR INHIBITION OF FASN

The present invention relates to compounds and composition for inhibition of FASN, their synthesis, applications, and antidotes. An illustrative compound of the invention is shown below: 3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Phis phenyl.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris methyl.6. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein Ris methyl.7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Ris hydrogen.8. The compound of claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Ris halogen.10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a substituted or unsubstituted 9-membered 6 claim 1 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 heteroatoms and said heteroatoms are independently O claim 1 , S claim 1 , or N.11. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris a substituted or unsubstituted 9-membered 6 claim 2 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 2 , 2 claim 2 , 3 claim 2 , or 4 heteroatoms and said heteroatoms are independently O claim 2 , S claim 2 , or N.12. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Ris a substituted or unsubstituted 9-membered 6 claim 3 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 3 , 2 claim 3 , 3 claim 3 , or 4 heteroatoms and said heteroatoms are independently O claim 3 , S claim 3 , or N.13. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris a substituted or unsubstituted 9-membered 6 claim 5 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 5 , 2 claim 5 , 3 claim 5 , or 4 heteroatoms and said heteroatoms are independently O claim 5 , S claim 5 , or N.23. The compound ...

NOVEL ONIUM SALT COMPOUND, RESIST COMPOSITION, AND PATTERN FORMING PROCESS

Sulfonium and iodonium salts of nitrogen-containing carboxylic acids are novel. The onium salt functions as an acid diffusion controlling agent in a resist composition, enabling to form a pattern of good profile with high resolution, improved MEF, LWR and DOF. 6. The resist composition of claim 3 , further comprising a nonionic nitrogen-containing compound.7. The resist composition of claim 3 , further comprising a surfactant which is insoluble or substantially insoluble in water and soluble in alkaline developer and/or a surfactant which is insoluble or substantially insoluble in water and alkaline developer.8. A pattern forming process comprising the steps of applying the resist composition of onto a substrate claim 3 , prebaking to form a resist film claim 3 , exposing the resist film to KrF excimer laser claim 3 , ArF excimer laser claim 3 , EB or EUV through a photomask claim 3 , baking claim 3 , and developing the exposed resist film in a developer.9. The pattern forming process of wherein the exposing step is by immersion lithography wherein a liquid having a retractive index of at least 1.0 is interposed between the resist film and a protection lens.10. The pattern forming process of claim 9 , further comprising the step of forming a protective film on the resist film claim 9 , and in the immersion lithography claim 9 , the liquid is interposed between the protective film and the projection lens. This non-provisional application claims priority under 35 U.S.C. §119(a) on Patent Application No. 2014-168155 filed in Japan on Aug. 21, 2014, the entire contents of which are hereby incorporated by reference.This invention relates to an onium salt compound of specific structure, a resist composition, typically chemically amplified resist composition comprising the salt, and a pattern forming process using the resist composition.While a number of recent efforts are being made to achieve a finer pattern rule in the drive for higher integration densities and ...

Dynamic control of colocalization of proteins

The present invention provides a method for controlling colocalization of two or more proteins in a cell. The method comprises expressing the proteins, scaffold RNA molecules having binding motifs for the proteins, and a trigger RNA molecule in the cell. In the presence of the trigger RNA molecule, a scaffold may be assembled (ON) by the scaffold RNA molecules via hybridization such that the proteins may be colocalized; or disassembled (OFF) such that the proteins may be separated and not colocalized. The proteins may provide a biological activity when colocalized or not colocalized.

Compound Having Effect Of Inhibiting Platelet Aggregation And Salt Thereof, And Composition For Preventing Or Treating Thrombotic Diseases, Containing Same

The present invention relates to a novel compound having an effect of inhibiting platelet aggregation and a salt thereof and, more specifically, to: a novel platelet aggregation inhibitor specifically inhibiting shear stress-induced platelet aggregation; a pharmaceutical composition containing the same as an active ingredient; and a preparation method therefor. 2. The compound of claim 1 , wherein the compound is selected from the following group:(6,7-Dihydrothieno[3,2-c]pyridin-5(4H)-yl)(3,4-dihydroxyphenyl)methanone;(3,4-Dihydroxyphenyl)(4-(5-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methanone;N-((4-(4-Fluorobenzyl)morpholin-2-yl)methyl)-3,4-dihydroxybenzamide;3,4-Dihydroxy-N-(2-oxotetrahydrothiophen-3-yl)benzamide;N,N′-(Nonan-1,9-diyl)bis(3,4-dihydroxybenzamide);(4-((4-Chlorophenyl)(pyridin-2-yl)methoxy)piperidin-1-yl)(3,4-dihydroxyphenyl)methanone;(S)-(4-((4-Chlorophenyl)(pyridin-2-yl)methoxy)piperidin-1-yl)(3,4-dihydroxyphenyl)methanone;(S)-Methyl-2-(3,4-dihydroxybenzamido)-3-(1H-indol-3-yl)propanoate;4-(3,4-Dihydroxybenzamido)-1-methyl-3-propyl-1H-pyrazole-5-carboxamide;2-Methyl-4-oxo-4H-pyran-3-yl 3,4-dihydroxybenzoate;(3,4-Dihydroxyphenyl)(4-phenylpiperazin-1-yl)methanone;(6,7-Dihydrothieno[3,2-c]pyridin-5(4H)-yl)(4-hydroxy-3-methoxyphenyl)methanone;2-Ethyl-4-oxo-4H-pyran-3-yl 4-hydroxy-3-methoxybenzoate;2-Methyl-4-oxo-4H-pyran-3-yl 4-hydroxy-3-methoxybenzoate;4-Hydroxy-3-methoxy-N-(4-methoxy-2-nitrophenyl)benzamide;N-(3-Ethynylphenyl)-4-hydroxy-3-methoxybenzamide;4-(4-(4-Hydroxy-3-methoxybenzamido)phenoxy)-N-methylpicolinamide;4-((4-Chlorophenyl)(pyridin-2-yl)methoxy)piperidin-1-yl)(4-hydroxy-3-methoxyphenyl)methanone;4-Hydroxy-N-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methyl)-3-methoxybenzamide;(6,7-Dihydrothieno[3,2-c]pyridin-5(4H)-yl)(2,5-dihydroxyphenyl)methanone;(4-((4-Chlorophenyl)(pyridin-2-yl)methoxy)piperidin-1-yl)(2,5-dihydroxyphenyl)methanone;N-((4-(4-Fluorobenzyl)morpholin-2-yl)methyl)-2,5-dihydroxybenzamide;(2,5-Dihydroxyphenyl)(4-( ...

AMPK Modulators

The present invention relates to compounds and pharmaceutically acceptable salts, esters and prodrugs of Formula (I) or (II): 220-. (canceled) This application is a continuation of U.S. application Ser. No. 13/571,218, filed Aug. 9, 2012, which is a continuation of U.S. application Ser. No. 12/365,671, filed Feb. 4, 2009, now U.S. Pat. No. 8,273,744, which claims the benefit of U.S. Provisional Application No. 61/026,001, filed on Feb. 4, 2008 and U.S. Provisional Application No. 61/051,200, filed on May 7, 2008, the contents of which are herein incorporated by reference.The AMP-activated protein kinase (AMPK) acts as an intracellular metabolic sensor in a variety of cells, where it monitors and responds to variations in the AMP:ATP ratio (Hardie et al., 67:821-855, 1998). Upon activation of AMPK, the enzyme phosphorylates a number of protein substrates to decrease further ATP usage by the cell. AMPK is a heterotrimeric complex consisting of a catalytic subunit (α) and two associated subunits (β and γ). Both the β and γ subunits are required for optimal activity of the α catalytic subunit. The AMPK complex is evolutionarily conserved and also can be found in yeast and plants. Mammalian AMPK is composed of different isoforms of subunits: α1, α2, β1, β2, γ1, γ2, and γ3 (Hardie and Hawley, 23:1112 1119, 2001). Different combinations of isoform subunits are activated differently in vivo, and most likely also differ in substrate utilization. AMPK activity is found in all tissues, including liver, kidney, muscle, lung, and brain (Cheung et al., 346:659-669, 2000).AMPK is recognized as a major regulator of lipid biosynthetic pathways due to its role in the phosphorylation and inactivation of key enzymes such as acetyl-CoA carboxylase, fatty acid synthase (Hardie and Carling, 246:259 273, 1997). More recent work has suggested that AMPK has a wider role in metabolic regulation (Winder and Hardie, 277:E1 10, 1999); this includes fatty acid oxidation, muscle glucose uptake, ...

ORGANIC LIGHT-EMITTING DEVICE, AND LIGHT-EMITTING MATERIAL AND COMPOUND USED THEREFOR

An organic light-emitting device having a light-emitting layer containing a compound represented by the general formula below has a high light emission efficiency. In the general formula, at least one of Rto Rrepresents a cyano group, at least one of Rto Rrepresents a 9-carbazolyl group, a 1,2,3,4-tetrahydro-9-carbazolyl group, a 1-indolyl group or a diarylamino group, and the balance of Rto Rrepresents a hydrogen atom or a substituent. 116-. (canceled)18. The method according to claim 17 , wherein the composition is a solution of a compound represented by the formula (1).19. The method according to claim 18 , which emits a delayed fluorescent light from the solution of a compound represented by the formula (1).20. The method according to claim 18 , which comprises irradiating the solution with a light.21. The method according to claim 17 , wherein the composition is a film of a compound represented by the formula (1).22. The method according to claim 21 , which emits a delayed fluorescent light from the film of a compound represented by the formula (1).23. The method according to claim 21 , which comprises irradiating the film with a light.24. The method according to claim 21 , which comprises injecting carriers to the film.25. The method according to claim 24 , which comprises injecting carriers to the film from a cathode and an anode.26. The method according to claim 17 , wherein at least one of Rto Rin the formula (1) represents a substituted or unsubstituted 9-carbazolyl group claim 17 , a substituted or unsubstituted 1 claim 17 ,2 claim 17 ,3 claim 17 ,4-tetrahydro-9-carbazolyl group claim 17 , a substituted or unsubstituted 1-indolyl group or a substituted or unsubstituted diarylamino group.27. The method according to claim 17 , wherein at least two of Rto Rin the formula (1) represent a substituted or unsubstituted 9-carbazolyl group claim 17 , a substituted or unsubstituted 1 claim 17 ,2 claim 17 ,3 claim 17 ,4-tetrahydro-9-carbazolyl group claim 17 , a ...

INDOLE CARBOXAMIDE COMPOUNDS

Disclosed are compounds of Formula (I): 117-. (canceled)19. The compound according to wherein:{'sub': 1', '3, 'Ris H or —CH;'}{'sub': 2', '3, 'Ris H, —CH, or cyclopropyl;'}{'sub': '3', 'Ris F or Cl;'}{'sub': '4', 'Ris H or F; and'}{'sub': '6', 'Ris H, F, or Cl.'}20. The compound according to wherein{'sub': '3', 'Ris F.'}21. The compound according to wherein:{'sub': '3', 'Ris Cl.'}22. The compound according to wherein:{'sub': '5', 'Ris H; and'}{'sub': '6', 'Ris H.'}27. A pharmaceutical composition comprising a compound according to or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier.28. A method for treating a disease comprising the administration to a subject in need thereof a therapeutically-effective amount of at least one compound according to or a pharmaceutically-acceptable salt thereof claim 18 , wherein said disease is selected from systemic lupus erythematosus (SLE) claim 18 , rheumatoid arthritis claim 18 , multiple sclerosis (MS) claim 18 , and Sjögren's syndrome. This continuation application claims the priority benefit of U.S. patent application Ser. No. 14/921,347 filed Oct. 23, 2015, which claims the benefit of U.S. Application Ser. No. 62/068,225, filed Oct. 24, 2014, which is incorporated herein it its entirety.The present invention generally relates to indole carboxamide compounds useful as kinase inhibitors, including the modulation of Bruton's tyrosine kinase (Btk) and other Tec family kinases such as Itk. Provided herein are indole carboxamide compounds, compositions comprising such compounds, and methods of their use. The invention further pertains to pharmaceutical compositions containing at least one compound according to the invention that are useful for the treatment of conditions related to kinase modulation and methods of inhibiting the activity of kinases, including Btk and other Tec family kinases such as Itk, in a mammal.Protein kinases, the largest family of human enzymes, encompass well over 500 ...