ЗАМЕЩЕННЫЕ БЕНЗИЛОКСИКАРБОНИЛГУАНИДИНЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ И СРЕДСТВО, ИНГИБИРУЮЩЕЕ NA+/H+-ОБМЕН

Настоящее изобретение относится к замещенным бензилоксикарбонилгуанидинам общей формулы I, где R(1), R(2) и R(3) независимо друг от друга обозначают водород, (С1-С8)-алкил, F, Cl, Br, I, OR(25), R(31)SOl-, где R(25) обозначает пиридил, хинолинил, изохинолинил; "l"= 2, R(31) обозначает -(С1-С8)-алкил; R(1), R(2) и R(3) независимо друг от друга обозначают -OR(67) или -NR(67)R(68); где R(67) и R(68) независимо друг от друга обозначают алкил с 1, 2, 3 или 4 С-атомами; R(4) и R(5) независимо друг от друга обозначают водород, F, Cl; R(6) и R(7) независимо друг от друга обозначают водород; Х обозначает кислород или NR(72), где R(72) обозначает водород или алкил с 1, 2, 3 или 4 С-атомами. Описан способ их получения. Соединения являются эффективными ингибиторами клеточного натрий-протонного антипорта (Na+/H+-обмен) и пригодны в качестве антиаритмических средств. 3 c. и 3 з.п. ф-лы.

ЗАМЕЩЕННЫЕ БИАРИЛЬНЫЕ СОЕДИНЕНИЯ ИЛИ ЗАМЕЩЕННЫЕ ПИРИДИНЫ И ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ НА ИХ ОСНОВЕ

Изобретение относится к биарильным соединениям или замещенным пиридинам формулы (I), где Х обозначает N или CR8, где R8 обозначает водород, галоген, фенил, алкил, алкокси, алкоксикарбонил, карбокси, формил или -NR4R5, где R4 и R5 обозначают водород, алкил, алкенил, циклоалкил, фенил, нафтил; R1a и R1в обозначают трифторметил, алкил, алкенил, алкинил, циклоалкил, алканоил; R2 обозначает алкил, алкенил, алкинил, циклоалкил; R3 обозначает гидрокси, трифторацетил, алканоил, алкенил; Аr обозначает ароматическое или гетероароматическое кольцо, например фенил, нафтил, пиридил, фуранил, тиофенил. Соединения формулы (I) обладают антагонистическим действием по отношению к рецептору глюкагона и могут быть использованы при лечении глюкагонмедиированных состояний, таких как диабет. 8 с. и 12 з.п. ф-лы, 2 табл.

АЗАБИЦИКЛЫ, МОДУЛИРУЮЩИЕ ИНГИБИРОВАНИЕ КЛЕТОЧНОЙ АДГЕЗИИ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ЛЕЧЕНИЯ

Изобретение относится к соединению формулы (I) где R1 представляет (i) R3-Z3- или (ii) R3-L3 -Ar1-L4-Z3-; R2 представляет водород; R3 представляет алкил; арил, необязательно замещенный одним или двумя заместителями из галогена и C1-4-алкила; арилалкил; R5 представляет водород; R7 и R7a представляют водород; R8 представляет водород; R9 представляет алкил; необязательно замещенный галогеном арил; гетероарил, содержащий до 2 гетероатомов, выбранных из атомов азота и кислорода, или алкил, замещенный арилом или гетероарилом; А1 представляет незамещенную C1-3-алкиленовую связь с линейной цепью; Ar1 представляет арилен, который может быть необязательно замещен С1-4-алкокси; или гетероарилдиил, содержащий до 2 гетероатомов, выбранных из атомов азота и кислорода; L1 представляет алкиленовую связь, которая необязательно замещена -N(R8)-С(=О)-R9, -N(R8 )-C(=О)-OR9, -N(R8)-SO2-R9; L3 представляет -NR5-C(=Z)-NR5-, -Z-, -NR5-, -NR5-C(=O)-O-, или -O-C(=О)-NR5-; L4 представляет алкиленовую связь; Z представляет ...

ЛИГАНДЫ РЕЦЕПТОРОВ ЭСТРОГЕНА

Изобретение относится к соединениям формулы (I)или их фармацевтически приемлемым солям. Технический результат: получены новые, которые могут быть использованы в качестве лигандов эстрогеновых рецепторов. 24 схемы, 360 пр., 6 н. и 15 з.п. ф-лы.

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 ...

КРИСТАЛЛИЧЕСКИЙ НАТРИЙ 1-(((1(R)-3-(2-(7-ХЛОР-2-ХИНОЛИНИЛ)ЭТЕНИЛ)ФЕНИЛ)-3-(2-(1-ГИДРОКСИ-1-МЕТИЛЭТИЛ)ФЕНИЛ)ПРОПИЛ)ТИО)МЕТИЛ)ЦИКЛОПРОПАНАЦЕТАТ

Изобретение относится к кристаллическому натрий 1-(((1(R)-(3-(2-(7-хлор-2-хинолинил)этенил)фенил)-3-(2-(1-гидрокси-1-метилэтил)фенил)пропил)тио)-метил)циклопропанацетату, который характеризуется следующими межплоскостными расстояниями (d), 18,60; 14,14; 8,63; 5,63; 4,73; 4,09; 3,71. Технический результат - получена новая форма соединения. 6 ил.

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 ...

ОПТИЧЕСКИ АКТИВНЫЕ ПРОИЗВОДНЫЕ БЕНЗОПИРАНА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ЛЕЧЕНИЯ ЧУВСТВИТЕЛЬНЫХ К ЭСТРОГЕНАМ ЗАБОЛЕВАНИЙ

Изобретение относится к новым оптически активным производньм бензопирана формулы где R и R независимо выбраны из группы, состоящей из гидроксила и радикала, который может преобразовываться in vivo в гидроксил, такой как ацилокси, -OR4, -OC(O)R7 или -OC(O)OR4 (где R4 представляет собой алкил, алкенил, алкинил или арил; и R7 представляет собой амино, алкиламино, аминоалкил и алкилсульфанил); и R3 представляет собой -СН2- или -СН2СН2-; или его фармацевтически приемлемая соль, где указанное соединение или соль являются оптически активными, поскольку содержат более 50% (по массе относительно всех стереоизомеров) 2S стереоизомеров. Эти соединения обладают ингибирующей активностью в отношении полового стероида и могут использоваться при лечении чувствительных к эстрогенам заболеваний, таких как рак молочной железы и рак эндометрия. Изобретение относится также к фармацевтической композиции на основе этих соединений и способу лечения чувствительных к эстрогенам заболеваний. Технический результат ...

ПРОИЗВОДНЫЕ ХИНОЛИНА, СПОСОБ ИХ ПОЛУЧЕНИЯ (ВАРИАНТЫ), ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ С ИХ ИСПОЛЬЗОВАНИЕМ

Описываются производные хинолина общей формулы (I), где R выбирают из метила, этила н-пропила, изопропила, н-бутила, R' выбирают из метила, метокси, фтора, хлора, брома, трифторметила и ОСНхFy, где х=0-2, у=1-3 при условии, что х+у =3, R" выбирают из водорода, фтора или хлора, при условии, что R" является фтором или хлором, только когда R' выбран из фтора и хлора, R4 выбирают из водорода или фармацевтически приемлемых неорганических или органических катионов; R5 выбирают из этила, н-пропила, изопропила, метокси, этокси, хлора, брома, трифторметила, ОСНхFy или ОСН2СНхFy, где х=0 -2, у=1-3 при условии, что х+у=3, R6 является водородом, а R5 и R6 вместе представляют собой метилендиокси, а также любой его таутомер. Описывается также фармацевтическая композиция, обладающая противоаутоиммунным и противовоспалительным действием, содержащая соединение общей формулы (I) вместе с фармацевтически приемлемым носителем, способы получения соединений формулы (I), и способ лечения млекопитающих, страдающих ...

ПРОИЗВОДНЫЕ БИЦИКЛИЧЕСКИХ АМИДОВ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ ПАТОЛОГИЧЕСКИХ И ВОСПАЛИТЕЛЬНЫХ СОСТОЯНИЙ

Описываются новые производные бициклических амидов общей формулы I, где R1 , R2, R3 и R4 выбраны (каждый) из водорода и фтора и, по меньшей мере, один и не более двух из них представляют собой фтор, R5 выбран из водорода и С1-С4-алкила, R6 выбран из водорода, С1-С4-алкила и гидроксигруппы или R5 и R6 вместе с углеродом кольца образуют карбонильную группу, R7 выбран из водорода и гидроксигруппы, R8 и R9 выбраны, каждый, из водорода С1-С4-алкила и цикло (С3 или С4)алкила или вместе с азотом образуют морфолиногруппу, их соли и сольваты. Описываются также фармацевтические композиции на основе соединений формулы I, которые находят применение в медицине, в частности, в качестве релаксантов основных мышц. Описывается также способ лечения патологических и воспалительных состояний. Соединения формулы I обладают значительно пониженной способностью вызывать седативный эффект и нарушение координации по сравнению с известными средствами. 10 с. и 21 з.п. ф-лы, 7 табл.

НОВЫЕ ПРОИЗВОДНЫЕ 1,2-ДИГИДРОХИНОЛИНА, ОБЛАДАЮЩИЕ АКТИВНОСТЬЮ СВЯЗЫВАНИЯ ГЛЮКОКОРТИКОИДНОГО РЕЦЕПТОРА

Настоящее изобретение относится к области органической химии, а именно к новым производным 1,2-дигидрохинолина общей формулы (1) или к их фармацевтически приемлемой соли, где Rпредставляет собой низшую алкильную группу; Rпредставляет собой атом водорода; Rи Rпредставляют собой каждый низшую алкильную группу; Rпредставляет собой низшую алкильную группу; Rпредставляет собой атом галогена, низшую алкильную группу, низшую алкоксигруппу, нитрогруппу; Х представляет собой -СО-, -C(O)NR- или -S(O)-; Rи/или Rмогут быть одинаковыми или различными и представляют собой каждый атом водорода, низшую алкильную группу, низшую алкенильную группу, низшую циклоалкильную группу, фенильную или нафтильную группу, насыщенный или ненасыщенный одноядерный 5- или 6-членный гетероциклил с одним или двумя гетероатомами, выбранными из атомов азота, кислорода и серы, и 3-5 атомами углерода в цикле, низшую алкоксигруппу, феноксигруппу; в случае когда Rи/или Rпредставляет собой низшую алкильную группу, низшую алкоксигруппу ...

КОНДЕНСИРОВАННЫЕ БИЦИКЛИЧЕСКИЕ КАРБОКСАМИДНЫЕ ПРОИЗВОДНЫЕ, ИСПОЛЬЗУЕМЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ СХСR2 ДЛЯ ЛЕЧЕНИЯ ВОСПАЛЕНИЙ

Настоящее изобретение относится к соединениям формулы I и к их фармацевтически приемлемым солям. Соединения настоящего изобретения могут быть использованы в качестве лекарственного средства, обладающего свойствами ингибитора CXCR2. В формуле I ! ! Х представляет собой -CR3=CR4-, -CR5=N-, -N=CR6-, -NR7- или -S-; R3, R4, R5 и R6 независимо представляют собой водород, F, Cl, Br, I; R7 представляет собой водород; Y1, Y2, Y3 и Y4 независимо представляют собой -CR8- или азот, при условии, что по меньшей мере два из Y1, Y2, Y3 и Y4 представляют собой -CR8-; где R8 представляет собой водород, F, Cl, Br, I; A представляет собой циклоалкил, имеющий 3, 4, 5, 6, 7 или 8 атомов углерода; бициклический частично насыщенный 9-членный циклоалкил; бициклический частично насыщенный 9-10-членный гетероцикл, в котором два атома на кольце представляют собой атомы кислорода; фенил; нафтил; 5-6-членный гетероарил, в котором один-три атома на кольце представляют собой атомы кислорода, серы и азота; 9-10-членный ...

ПРОИЗВОДНЫЕ БЕНЗОЦИКЛОГЕПТАНА И БЕНЗОКСЕПИНА

Изобретение относится к соединению формулы (I), включая любые его стереохимические изомерные формы, или его фармацевтически приемлемую соль,где А является фенилом или 6-членным ароматическим гетероциклом, содержащим 1 или 2 атома азота; где указанный фенил или 6-членный ароматический гетероцикл необязательно могут быть сконденсированы с фенилом; Z является CHили O; Rявляется галогеном, гидроксилом, Cалкилом, Cалкилокси, или, если A является фенилом, два соседних заместителя Rмогут быть взяты вместе с получением радикала формулы: -O-CH-O- (a-1) или -O-CH-СН-O- (a-2); Rявляется водородом или Cалкилом; Rи Rкаждый независимо является водородом, Cалкилом, CалкилоксиCалкилом или фенилCалкилом; или Rи R, взятые вместе с атомом азота, к которому они присоединены, образуют радикал формулы (b-1) или (b-2)где Xявляется CHили CHOH; и Xявляется CH, O или NR; Rявляется водородом, галогеном, Cалкилом или Cалкилокси; Rявляется водородом, Cалкилом, Cалкилкарбонилом; n равно целому числу 0, 1 или 2; при ...

СПОСОБ ПОЛУЧЕНИЯ АНТАГОНИСТОВ ЛЕЙКОТРИЕНА, ДИЦИКЛОГЕКСИЛАМИНОВАЯ СОЛЬ, СПОСОБЫ ПОЛУЧЕНИЯ КРИСТАЛЛИЧЕСКОЙ НАТРИЕВОЙ СОЛИ И 1-/МЕРКАПТОМЕТИЛ/- ЦИКЛОПРОПАНУКСУСНОЙ КИСЛОТЫ, КРИСТАЛЛИЧЕСКОЕ СОЕДИНЕНИЕ

Описывается способ получения соединения формулы (I), где НЕТ представляет собой 7-хлорхинолин-2-ил или 6,7-дифторхинолин-2-ил, отличающийся тем, что осуществляют генерирование дилитиевого дианиона 1-(меркаптометил)циклопропануксусной кислоты реакцией 1-(меркаптометил)циклопропануксусной кислоты с литиевым основанием; взаимодействие указанного дианиона с соединением формулы (II), где НЕТ имеет значение, указанное выше, и L означает арилсульфонил или алкилсульфонил, с последующей обработкой кислотой для генерации свободной кислоты соединения формулы (I), и необязательно превращают свободную кислоту в соответствующую соль дициклогексиламина и затем в натриевую соль. Технический результат - создание эффективного способа, обеспечивающего повышенный суммарный выход продукта и возможность получения кристаллической формы. 5 с. и 9 з.п.ф-лы., 6 ил.

[N'-(Изо)хинолилметилен]гидразиды 3-метокси-13,17-секоэстра-1,3,5(10)-триен-17-овой кислоты

Изобретение относится к новым [N'-(изо)хинолилметилен]гидразидам 3-метокси-13,17-секоэстра-1,3,5(10)-триен-17-овой кислоты указанной ниже общей формулы, которые обладают антипролиферативной активностью в отношении клеток рака молочной железы MCF-7 и могут найти применение в медицине, ветеринарии, химико-фармацевтической промышленности и биотехнологии. 1 з.п. ф-лы, 4 табл., 22 пр. R1 и R2=Н, Me, ОМе, Cl или F ...

КОНДЕНСИРОВАННЫЕ БИЦИКЛИЧЕСКИЕ ГЕТЕРОАРОМАТИЧЕСКИЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ МОДУЛЯТОРОВ АКТИВНОСТИ TNF

Изобретение относится к области органической химии, а именно к гетероциклическому соединению формулы (IIB) или его фармацевтически приемлемой соли, где q равно 1; А обозначает C-R; G обозначает остаток пиридазинильного кольца; Е обозначает -О-, -СН- или -СН(СН)-; Q обозначает -СН-; Z обозначает водород; V обозначает N; Rобозначает водород; Rобозначает водород, метил или дифторметоксигруппу; Rобозначает водород; Rобозначает гидрокси(С-С)алкил; и Rобозначает водород. Также изобретение относится к фармацевтической композиции на основе соединения формулы (IIB), применению соединения формулы (IIB) и способу лечения и/или предупреждения ревматоидного артрита или болезни Крона. Технический результат: получены новые гетероциклические соединения, обладающие свойствами модулятора передачи сигнала TNFα. 4 н. и 3 з.п. ф-лы, 12 пр.

СОЕДИНЕНИЯ И СПОСОБЫ МОДУЛИРОВАНИЯ КИНАЗ И ПОКАЗАНИЯ К ПРИМЕНЕНИЮ УКАЗАННЫХ СОЕДИНЕНИЙ И СПОСОБОВ

... 1. Соединение, имеющее химическую структуру формулы I ! ! Формула I ! или его соль, пролекарство, таутомер или изомер, ! где Ar представляет собой необязательно замещенный гетероарил; ! R1 в каждом случае независимо выбирают из группы, включающей галоген, необязательно замещенный низший алкил, необязательно замещенный низший алкенил, необязательно замещенный низший алкинил, необязательно замещенный циклоалкил, необязательно замещенный гетероциклоалкил, необязательно замещенный арил, необязательно замещенный гетероарил, -NO2, -CN, -O-R5, -N(R5)-R6, -C(X)-N(R5)-R6, -C(X)-R7, -S(O)2-N(R5)-R6, -S(O)n-R7, -O-C(X)-R7, -C(X)-O-R5, -C(NH)-N(R8)-R9, -N(R5)-C(X)-R7, -N(R5)-S(O)2-R7, -N(R5)-C(X)-N(R5)-R6 и -N(R5)-S(O)2-N(R5)-R6; ! m представляет собой 0, 1, 2, 3, 4 или 5; ! n представляет собой 0, 1 или 2; ! R2 представляет собой водород, низший алкил или галоген; ! L2 выбирают из группы, включающей -S(O)2-, -C(X)-, -C(X)-N(R10)- и -S(O)2-N(R10)-; ! R3 представляет собой необязательно замещенный низший ...

ЛИГАНДЫ РЕЦЕПТОРОВ ЭСТРОГЕНА

Изобретение относится к соединениям формулы (I)или их фармацевтически приемлемым солям. Технический результат: получены новые, которые могут быть использованы в качестве лигандов эстрогеновых рецепторов. 24 схемы, 360 пр., 6 н. и 15 з.п. ф-лы.

НОВЫЕ ПРОИЗВОДНЫЕ 1-2-ДИГИДРОХИНОЛИНА, ОБЛАДАЮЩИЕ АКТИВНОСТЬЮ СВЯЗЫВАНИЯ С ГЛЮКОКОРТИКОИДНЫМ РЕЦЕПТОРОМ

... 1. Соединение, представленное следующей общей формулой (1), или его соли: ! ! где кольцо Х представляет собой бензольное кольцо или пиридиновое кольцо; ! R1 представляет собой атом галогена, низшую алкильную группу, которая, по меньшей мере, может иметь заместитель, гидроксильную группу, низшую алкоксигруппу, которая, по меньшей мере, может иметь заместитель, низшую алкенилоксигруппу, которая, по меньшей мере, может иметь заместитель, низшую алкилкарбонильную группу, аминогруппу, нитрогруппу или цианогруппу; ! p представляет собой целое число от 0 до 5; ! в случае, если p равен от 2 до 5, каждый остаток R1 может быть одной и той же группой или различными группами; ! R2 представляет собой атом галогена, низшую алкильную группу, которая, по меньшей мере, может иметь заместитель, гидроксильную группу, сложный эфир гидроксильной группы или низшей алкоксигруппы, которая, по меньшей мере, может иметь заместитель; ! q представляет собой целое число от 0 до 2; ! в случае, если q равен 2, каждый ...

4-ГИДРОКСИБЕНЗОМОРФАНЫ

... 1. Соединение формулы ! ! в которой ! А выбран из -C(=О)NH2 и -C(=S)NH2; ! R2 и R2a оба представляют собой атом водорода или, взятые вместе, R2 и R2a представляют собой =О; ! R3 выбран из атома водорода, низшего алкила, алкенила, арила, гетероциклила, бензила и гидроксиалкила; ! R4 выбран из атома водорода, гидрокси, амино, низшей алкокси, С1-С20алкила и С1-С20алкила, замещенного гидроксилом или карбонилом; ! R11 представляет собой атом водорода; ! R12 выбран из атома водорода, гидрокси, низшей алкоксигруппы и -NR13R14; или ! радикалы R11 и R12 вместе образуют карбонильный или винильный заместитель; ! R13 и R14 выбраны независимо из атома водорода и C1-C7 углеводородной группы, и ! пунктирная линия обозначает необязательную двойную связь. ! 2. Соединение по п.1, в котором ! R2 и R2a представляют собой атом водорода; ! R3 выбран из атома водорода, циклопропила и циклобутила, винила и тетрагидрофуранила; ! R4 выбран из атома водорода и гидроксила; ! R11 представляет собой атом водорода; !

КОНДЕНСИРОВАННЫЕ БИЦИКЛИЧЕСКИЕ ГЕТЕРОАРОМАТИЧЕСКИЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ МОДУЛЯТОРОВ АКТИВНОСТИ TNF

ГЕНЕТИЧЕСКИЕ МАРКЕРЫ, АССОЦИИРОВАННЫЕ С ОТВЕТОМ НА АНТИАГОНИСТЫ РЕЦЕПТОРА CRTH2

СПОСОБЫ ПРИМЕНЕНИЯ АКТИВАТОРОВ ПИРУВАТКИНАЗЫ

АНТАГОНИСТЫ TLR7/8 И ИХ ПРИМЕНЕНИЕ

СЕЛЕКТИВНЫЕ К BCL-2 АГЕНТЫ, ВЫЗЫВАЮЩИЕ АПОПТОЗ, ДЛЯ ЛЕЧЕНИЯ РАКА И ИММУННЫХ ЗАБОЛЕВАНИЙ

... 1. Соединение формулы Iили его терапевтически приемлемая соль, пролекарство или соль пролекарства,где Аявляется N или С(А);один, или два, или три, или каждый из А, В, Dи Eнезависимо выбраны из R, OR, SR, S(O)R, SOR, C(O)R, C(O)OR, OC(O)R, NHR, N(R), C(O)NHR, C(O)N(R), NHC(O)R, NHC(O)OR, NRC(O)NHR, NRC(O)N(R), SONHR, SON(R), NHSOR, NHSONHRили N(CH)SON(CH)R, а остальные независимо выбраны из H, F, Cl, Br, I, CN, CF, C(O)OH, C(O)NHили C(O)ORиYпредставляет собой H, CN, NO, C(O)OH, F, Cl, Br, I, CF, OCF, CFCF, OCFCF, R, OR, C(O)R, C(O)OR, SR, NH, NHR, N(R), NHC(O)R, C(O)NH, C(O)NHR, C(O)N(R), NHS(O)Rили NHSOR;или Ви Yвместе с атомами, с которыми они связаны, образуют имидазол или триазол иодин, или два, или каждый из А, Dи Eнезависимо выбраны из R, OR, SR, S(O)R, SOR, C(O)R, C(O)OR, OC(O)R, NHR, N(R), C(O)NHR, C(O)N(R), NHC(O)R, NHC(O)OR, NHC(O)NHR, N(CH)C(O)N(CH)R, SONHR, SON(R), NHSOR, NHSONHRили N(CH)SON(CH)R, а остальные независимо выбраны из H, F, Cl, Br,I, CF, C(O)OH, C(O)NHили C(O)OR; ...

ПРОИЗВОДНЫЕ 2,6-ХИНОЛИНИЛА И 2,6-НАФТИЛА, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНГИБИТОРОВ VLA-4

... 1. Соединение, имеющее формулу I, или его фармацевтически приемлемая соль, где Х - представляет собой N или СН; R1 - представляет собой циклоалкил, арил, гетероцикл, аралкил, гетероциклический-алкил, или окси-производное, или группу имеющую формулу: R2 - представляет собой NR4R5, OR4 или –C(=O)NR5R6; R3 - представляет собой тетразол, -CN, CH2OH или -СО-R7; R4 - представляет собой Н, -G1-R8 или группу, имеющую формулу: R5 - представляет собой Н, C1-4-алкил, или NR4R5-группу, являющуюся гетероциклом, или –N=CR9R10; R6 - представляет собой арил, гетероцикл, циклоалкил или аралкил; R7 - представляет собой гидрокси, амино, гидроксиламино, или окси-производное или аминопроизводное; R8 - представляет собой арил, гетероцикл, циклоалкил, аралкил или -NH-арил; R9 - представляет собой арил; и R10 - представляет собой эфир; при условии, что когда Х - представляет собой СН, тогда R1 представляет собой циклоалкил, арил, гетероцикл, аралкил, гетероциклический арил или группу, имеющую формулу: при условии ...

VERFAHREN ZUR HERSTELLUNG VON NEUEN 1,4-DIHYDROCHINOLINEN SOWIE IHRE VERWENDUNG ALS ARZNEIMITTEL

Thioamides - as gastric acid secretion inhibitors

Cpds. (I): (where R1 is 2-pyridyl, 2- or 4-pyrimidyl, 2-pyrazinyl, 2-pyrrolyl, 2-quinolyl, or 2- or 4-thiazolyl; and (a) R2 is H, alkyl, alkenyl, Ph or PhCH2 and R3 is dialkylamino-, N-alkyl-N-phenyl-amino, pyrrolidino-piperidino-, morpholino- or N-alkyl-piperazino, methylamino; (b) R2 is H, alkyl, alkenyl or Ph opt. substd. by halogen. Alkyl or alkoxy and R3 is (3-6C)-cycloalkylamino or (3-6C)-cycloalkylmethylamino; (c) R2 is (CH2)m NR4R5, m = 0 or 1, and R4 and R5 are alkyl or NR4R5 is piperidino, pyrrolidino, or N-alkylpiperazino and R3 is NH-(CH2)n (3-6C)-cycloalkyl or NR6R7; R6 and R7 are H or alkyl; n is 0 or 1, (d) R2 is (CH2)mOR8, m is 0, 1 or 2, R8 is alkyl, allyl or cyclopropanemethyl and R3 is PhNH, NH(CH2)n (3-6C)-cycloalkyl or NR9R10 and R9 and R10 is H or alkyl, and n is 0 or 1; (e) R2 is H, alkyl, alkenyl, alkoxy, allyloxy, cyclopropanemethoxy, Ph, PhCH2 or (CH2)n NR11R12; n is 0 or 1 and R11 and R12 are alkyl or NR11R12 is piperidino, pyrrolidino, morpholino or N-alkyl-( ...

8-(BIARYL)CHINOLIN-PDE4-INHIBITOREN

BENZIMIDAZOLE, UND VERFAHREN ZU DEREN HERSTELLUNG, DEREN FORMULIERUNG UND VERWENDUNG ALS MAGENSAEURESEKRETIONSHEMMENDE VERBINDUNGEN.

(ALPHA)-SUBSTITUIERTE 4-(CHINOLIN-2-YL-METHOXY)PHENYLESSIGSAEUREN UND -ESTER, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG IN ARZNEIMITTELN

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

Thioformamidderivate.

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

CHINOLINDERIVATE

VERFAHREN ZUR HERSTELLUNG VON SUBSTITUIERTEN TETRALINEN, CHROMANEN UND VERWANDTEN VERBINDUNGEN, DIE BEI DER BEHANDLUNG VON ASTHMA VERWENDET WERDEN KOENNEN

PIPERIDINE COMPOUNDS

A PROCESS FOR THE PREPARATION OF NOVEL HETEROCYCLIC AMINOALCOHOLS

... 1,203,810. Heterocyclic amino-alcohols. DEUTSCHE GOLD - UND SILBERSCHEIDEANSTALT. 29 Dec., 1967 [30 Dec., 1966 (2)], No. 59037/67. Heading C2C. Novel compounds of formula in which the radicals R 1 -R 4 are H, halo, 1-6C alkyl, aralkyl, phenyl, OH, 1-6C alkoxy, nitro or 1-6C alkoxycarbonyl; R 5 and R 6 are H or methyl; R 7 and R 8 are H, halo, 1-6C alkyl, 1-6C alkoxy or phenyl; X is a mono- or bi-cyclic heterocyclic ring system having 1-4 heteroatoms, 5-6 ring members in each ring and which may contain one or more carbonyl groups and Y is O or a hydrogen atom and a hydroxyl group; their salts and quaternary ammonium derivatives are prepared by (1) reacting II with III in a solvent together with HCHO or a HCHO donor; (2) reacting IV or V with III; or (3) reacting VI with VII in the presence of a base followed in any of (1)-(3) by reduction of the oxo group to the hydroxy group if desired (R 9 and R 10 are 1-6C alkyl, W is halo and V is NH 2 -).

Improvements in or relating to the production of heterocyclic substituted phenacylpyridines

Heterocyclic substituted phenacylpyridines of the general formula where R is a pyridine, benzopyridine or alkylpyridine radical, R1 is an aryl radical and Z is the residue of a heterocyclic ring, are prepared by mixing together in an inert anhydrous organic solvent o -halophenacyl pyridine and a secondary heterocyclic amine, preferably at a temperature of 20 DEG to 25 DEG C. Suitable o -halophenacyl pyridines are: the o -chloro- and o -bromo-phenacyl pyridines, the corresponding benzopyridines and similar derivatives of the alkyl pyridines, such as those from 6-methyl pyridine, 4 : 6-dimethyl pyridine and 3-ethyl-6-methyl pyridine. The radical R1 may carry substituent radicals such as chlorine, bromine, methyl, methoxy, nitro and carbethoxy. Suitable heterocyclic secondary amines are piperidine, piperazine, morpholine, thiomorpholine, tetrahydroisoquinoline, thiazoline and pyrollidine. Preferred solvents include benzene, diethyl ether, dibutyl ether, toluene, anisol ...

PREPARATION OF DIAMINOBENZHYDROLS

... 1398075 Preparation of diaminobenzhydrols IMPERIAL CHEMICAL INDUSTRIES Ltd 31 Aug 1972 [2 Sept 1971] 40968/71 Heading C2C Diaminohydrols are produced by reducing the corresponding ketones by means of zinc dust and potassium hydroxide in a lower alcohol medium (i.e. one comprising 1-4 carbon atoms). Examples describe the reduction of Michler's ketone and the corresponding bis - (diethylamino) compound, bis - [2,3,6,7- tetrahydro - 1H,5H - benzo[ij]quinolizin - 9 - yl] ketone and bis-[1,2,3,4-tetrahydro-1-methylquinoline-5-yl]ketone ...

HYDRATROPIC ACID DERIVATIVES AND PREPARATION THEREOF

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

QUINOLINE DERIVATIVES

CHEMICAL COMPOUNDS

Carboxylic acid amides derived from aza compounds

Carboxylic acid amides derived from aza compounds are prepared by heating aza compounds having at least 2 condensed rings and no nuclear keto groups, and no other hetero atom besides nitrogen in the molecule, the aza-nitrogen standing in a 6-membered ring, and which contain at least one reactive hydrogen atom attached to nitrogen, with esters of enolizable keto-carboxylic acids Suitable starting materials on the one hand are primary or secondary amino compounds of azanaphthalenes, azaphenanthrenes (cf. Specification 451,932), azanthracenes, diazaphenanthrenes, azatriphenylene, diaza- and triaza-triphenylenes, azachrysenes, benzazapyrenes, azaperylenes, azacarbazoles and azabenzanthracenes; and on the other hand carboxylic acid esters of the formulae R.CO.CHR<1>.X or wherein R is any organic radicle combined to the CO group by means of carbon, R<1> is hydrogen or an organic radicle, and X is an esterified carboxylic group. Reaction is preferably effected in a diluent.

Electrophotographic material

... 943,266. Electrophotographic production of printing plates. KALLE A. G. Aug. 15,1960 [Aug. 20, 1959], No. 28193/60. Drawings to Specification. Heading G2H. [Also in Divisions C2, C3 and H1] The Specification describes various solvents suitable for removing the unexposed parts of a xerographic image on a material comprising a photoconductive keton resin after development with a pigmented resin powder. Such solvents are (1) 5 parts of 85% phosphoric acid, 30 parts of isopropanol and 65 parts of water, (2) 2. 5% hydrochloric acid, and (3) 2 parts of 5% phosphoric acid and 1 part of ethanol. The plate is then rinsed with water, wiped with aqueous phosphoric acid or an alkali metal phosphate, and inked with greasy ink for use as a printing plate.

HETEROCYCLIC COMPOUNDS

PYRIDINE DERIVATIVES

The present invention relates to compounds of formula I I in which formula I X stands for O, S, R1 and R2 which can be the same or different stand for hydrogen, straight or branched, saturated or unsaturated, unsubstituted or substituted C1-C8-alkyl, or for ar-C1-C4-alkyl, aryl and ar being unsubstituted or substituted phenyl; R3, R4, R5, and R6 are the same or different and stand for hydrogen, halogen, pseudo halogen, cyano, nitro, amino, carboxy, hydroxy, alkyl, alkoxy; or R5 and R6 form an aromatic ring which is fused to the pyridyl ring, and which aromatic ring may substituted; provided that R1 and R2 cannot be hydrogen at the same time, and provided that when R5 and R6 both are chlorine and R1 is hydrogen, then R2 cannot be n-propyl; and salts and bioreversible derivatives thereof. The compounds of formula I are useful in the human and veterinary therapy, as they exert specific 5-lipoxygenase inhibition.

DERIVATIVES OF 4-OXO-1, 4-DIHYDRONICOTINIC ACID

Preparation of -alkylated acetic acid derivatives

This invention provides a process for preparing a alpha -alkylated acetic acid derivative represented by the formula (II) wherein Z is -COOR or -CN in which R is straight-chain or branched-chain alkyl, cycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted aralkyl, R' is substituted or unsubstituted straight-chain or branched-chain alkyl or alkenyl, and Y is an optionally substituted heterocyclic group or optionally substituted aromatic group, the process comprising subjecting an acetic acid derivative represented by the formula Y-CH2-Z (I) wherein Y and Z are as defined above to electrolytic reduction in the presence of an alkylating agent.

OLEFINE DERIVATIVES

QUINOLINE DERIVATIVES

Chemical compounds

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

PERFLUOROALKYL COMPOUNDS CONTAINING THIO GROUPS AND FIRE-FILIGHTING COMPOSITIONS CONTAINING THEM

The aqueous, film-forming concentrates for extinguishing or preventing fire by suppressing the evaporation of flammable liquids contain (A) non-anionic compounds containing perfluoroalkylalkylenethio groups, (B) anionic fluorinated surfactants, (C) ionic fluorine-free surfactants, (D) non-ionic fluorine-free surfactants, (E) non-aqueous solvents and (F) water. The concentrates are stable, very effective even at low concentrations and, by reason of their low surface tension and the high spreading rate, have a very great sealing capacity for flammable vapours and gases. They can be used as aerosols or mixed with water for extinguishing fires.

Novel compounds, methods for their manufacture, and uses thereof

Synthetic cannabinoid analogue compounds of formula (I), wherein X is a group as defined herein. Also provided is a pharmaceutical composition of compounds of formula (I). Also provided is a compound of formula (I), or pharmaceutical composition, for use in a method of treatment, or for use as a medicament; which may be for use in the treatment of, or for use as a medicament for treating, epilepsy, generalised seizure, tonic-clonic seizure. Also provided is a method of preparing a compound of formula (I), comprising reacting a compound of formula (II) with a compound of formula (III), both defined herein. The method may use a palladium catalyst. Also provided is a method of preparing compounds of formula (I), comprising reacting a compound of formula (II) with bis(pinacolato)diboron (B2pin2), and reacting the product of that with a compound of formula (IV). The steps of the method may use a palladium catalyst. Also provided is an intermediate compound of formula (II), for use in the preparation ...

SUBSTITUTED TETRARINS CHROMANS & RELATED COMPOUNDS IN THE TREATMENT OF ASTHMA,ARTHRITIS ETC.

Polar-substituted hydrocarbons

Quinoline derivatives and use thereof as mycobacterial inhibitors

Antibacterial quinoline derivatives

Antibacterial quinoline derivatives

Hydroxamic acid derivatives as inhibitors of the production on human cd23 and of the tnf release

Substituted benzaldehyde compounds and methods fortheir use in increasing tissue oxygenation

Heteroaryl derivatives and uses thereof

Substituted tetralins, chromans and related compounds in the treatment of asthma, arthtitits and related diseases.

Substituted tetralins, chromans and related compounds ...

Quinoline derivatives.

The invention is related to compounds of general formula (I), wherein R is methyl, ethyl, n-propyl, iso-propyl, n-butyl or allyl; R' is methyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, or OCHxFy, wherein X= O-2, y=1-3 with the proviso that x + y = 3; R" is hydrogen, fluoro or chloro; with the proviso that R" is fluoro or chloro only when R' is fluoro; R4 is hydrogen or pharmaceutically acceptable inorganic or organic cations; Rs is ethyl, n-propyl, iso-propyl, methoxy, ethoxy, chloro, bromo, trifluoromethyl, OCHxFy, or OCH2CHxFy wherein x = 0-2, y =1-3 with the proviso that x + y = 3; Re is hydrogen; or Rs, and R" taken together are methylenedioxy; and any tautomer thereof. The invention also relates to pharmaceutical compositions containing a compound of general formula (I) together with a pharmaceutically acceptable carrier. Included are also processes for the preparation of the compounds of formula (I), as well as methods for the treatment of mammals suffering from diseases resulting ...

Substituted benzaldehyde compounds and methods fortheir use in increasing tissue oxygenation

Retroviral protease inhibitors.

The invention relates to certain retroviral protease inhibitors, ...

Quinoline derivatives and use thereof as mycobacterial inhibitors.

Antibacterial quinoline derivatives

Antibacterial quinoline derivatives

Polar-substituted hydrocarbons

Hydroxamic acid derivatives as inhibitors of the production of human CD23 and of the tnf relaease.

Compounds of formula (i)wherein: r is methyl substituted by one to three groups selected from alkyl, aryl, alkenyl, and alkynyl, n is 0 or 1, r1 is arylmethyl or heterocyclmethyl, r2 is alkyl, alkenyl, cycloalkyl or cycloalkenyl, and r3 is hydrogen, alkyl, alkenyl, alkynyl or aryl; are useful in the treatment of disorders mediated by s-cd23.

Quinoline-2-carboxylic acid derivatives and its use as excitatory amino acids antagonist.

The (+)enantiomer of e 4-(4-acetylamino-phenylcarbamoylmethylene)-5,7-dichloro-1,2,3,4-tetrahydro quinoline 2-carboxylic acid and salt thereof which are antagonist of excitatory amino acids, to processes for their preparation, to pharmaceutical compositions containing them, and to their use in medicine.

Nitrogen-containing heterocyclic compound and agricultural fungicide

Quinoline derivatives

Antibacterial quinoline derivatives

Antibacterial quinoline derivatives

Quinoline derivatives and use thereof as mycobacterial inhibitors

Substituted aralkyl derivatives

Nitrogen-containing heterocyclic compound and agricultural fungicide.

Heteroaryl derivatives and uses thereof

2-Quinolinyl-acetic acid derivatives as HIV antiviral compounds

Napht-2-ylacetic acid derivatives to treat AIDS

Substituted benzaldehyde compounds and methods fortheir use in increasing tissue oxygenation

Hydroxamic acid derivatives as inhibitors of the production of human cd23 and of the tnf release.

Substituted aralkyl derivatives.

Dérivatives of thioformamide.

Quinolines 2-substituted for the treatment of the leishmanioses

"Thioformamide derivatives".

1,2,4-substituted 1,2,3,4-tetrahydro-and 1,2 dihydro-quinoline and 1,2,3,4-tetrahydroquinoxaline derivatives as CETP inhibitors for the treatment of atherosclerosis and obesity.

"Thioformamide derivatives".

Process of production of substituted tetralin derivatives, chromanes and compounds related.

Substituted aralkyl derivatives

Nitrogen-containing heterocyclic compound and agricultural fungicide.

Napht-2-ylacetic acid derivatives to treat AIDS

Hydroxamic acid derivatives as inhibitors of the production on human cd23 and of the tnf release

Process for Preparing Pitavastatin, Intermediates and Pharmaceuctically Acceptable Salts Thereof

Processes for preparing pravastatin, intermediates and pharmaceutically acceptable salts thereof are provided Crystalline forms of pravastatin, intermediates and pharmaceutically acceptable salts thereof are also disclosed.

Method for preparation of pitavastatin and its pharmaceutical acceptable salts thereof

The present invention discloses a compound, which is alkali or alkaline earth metal salts of pitavastatin, wherein the alkali or earth metal comprise one or more of magnesium, zinc, potassium, strontium and barium.

Triglyceride-lowering agent and hyperinsulinism-ameliorating agent

The present invention is directed to a triglyceride-lowering agent, exhibiting excellent triglyceride-lowering effect and a hyperinsulinemia-ameliorating agent. The triglyceride-lowering agent and hyperinsulinemia-ameliorating agent are characterized by containing a pitavastatin compound, and amlodipine or a salt thereof.

Cadherin-11 inhibitors and methods of use thereof

Cadherin-11 inhibitors and methods for the prevention and treatment of cadherin-11 related diseases are described herein. Cadherin-11 related diseases include cancer and rheumatoid arthritis.

Quinoline derivatives as anti-cancer agents

Quinoline derivatives showing anticancer activities against cancer cell lines of hepatocellular carcinoma (Hep3B), lung carcinoma (A549), esophageal squamous cell carcinoma (HKESC-1, HKESC-4 and KYSE150). The quinoline derivatives have a backbone structure of the following formulas:

Process and intermediate compounds useful in the preparation of statins

There is provides a process for the preparation of a compound of formula (7): wherein R is an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; provides that R is not a compound of Formula (a): wherein R a represents an alkyl group, such as a C 1-16 alkyl group, and preferably an isopropyl group; R b represents an aryl group, preferably a 4-fluorophenyl group; R c represents hydrogen, a protecting group or an alkyl group, such as a C 1-16 alkyl group, and preferably a methyl group; and Rd represents hydrogen, a protecting group or a SO 2 R e group where R e is an alkyl group, such as a C 1-16 alkyl group, and preferably a methyl group.

Method for preparing an intermediate of pitavastatin or of the salt thereof

The present invention relates to a method for preparing (4R,6S)-(E)-6-[2-(2-cyclopropyl)-4-(4-fluorophenyl)quinolin-3-yl)-vinyl-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid ester derivative, which is an intermediate of pitavastatin or of the salt thereof, into a crystalline solid form. In addition, the present invention relates to a novel solvate of the intermediate, and to a method for preparing pitavastatin or the salt thereof using the intermediate.

COMPOUNDS DERIVED FROM ARTESUNATE, PREPARATION PROCESS, PHARMACEUTICAL COMPOSITION AND USE OF THE RESPECTIVE MEDICINE

The present invention refers to new compounds represented by the general formula (I) where X is represented by the general formula (II) and Y is represented by the general formula (III). The relation X to Y may vary from 1:1 to 1:7. The radicals R, R, R, R, R, and Rin formula (II) are represented by: R═H, CF, CH, OCH, NH, halogen; R═H, CH, NH, halogen, NH—CHCH(CH)N(CH)(CHCHOH), CH(OH)-2(CHN), NH—R—N—(CH); R═H, m-OCHCF, NH; R═H, CH, OCH, NH, halogen; R═H, CH, CF, NH, halogen; R═H, CF, CH, NH, halogen, NH—R—N—(CH), NHCH(CH) (CH)NH; R═(CH), (CH), CHCHCH, (CH), (CH), CHCH(CH), (CH), (CH), (CH), (CH); R═CHCH(CH), CHCH(CH)CHCH, (CH), (CH), (CH), (CH)O(CH). This invention also refers to a process of preparation of these compounds (formula I), and antiparasitic pharmaceutical compositions thereof. 2. Compounds according to claim 1 , characterized by the fact that R═H; R═NHCH(CH)(CH)N(CH); R═R═R═H and R═Cl; and the relation X to Y equals 1:1.3. Compounds according to claim 1 , characterized by the fact that R═CF3; R═CH(OH)-2-(CHN); R═R═R═H and R═CFand the relation X to Y equals 1:1.4. Compounds according to claim 1 , characterized by the fact that R═R═R═R═H; R═OCHand R═NHCH(CH)(CH)NH; and X to Y equals 1:2.5. Preparation process of artesunate derived compounds claim 1 , as defined by claim 1 , characterized by the fact it comprises the following stages:a) solubilization of quinoline, represented by the general formula II, as a free base form in organic solvents;b) solubilization of artesunate, represented by the general formula III, in organic solvents;c) addition of the artesunate solution (stage b) to the quinoline solution (stage a) in order to obtain derivatives of artesunate salts of quinolines;d) solvent evaporation for salt precipitation;e) salt filtration in order to obtain derivatives of artesunate salts of quinolines as a solid product. Its effectiveness ranges from 80 to 96%.6. Preparation process of artesunate derivatives according to claim 5 , characterized by ...

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 ...

SUBSTITUTED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS

The present invention relates to sodium channel inhibitors of Formula (I): 2. The compound of claim 1 , wherein Ris alkyl of 1-3 carbon atoms or phenyl optionally substituted by halo.3. The compound of claim 2 , wherein R claim 2 , Rand Rare independently chosen from hydrogen and halo.4. The compound of claim 3 , wherein Ris alkyl of 1-6 carbon atoms.5. The compound of claim 4 , wherein X is a covalent bond claim 4 , —C(O)O— claim 4 , or heteroaryl claim 4 , Y is methylene claim 4 , and Z is cycloalkyl or phenyl claim 4 , both of which are optionally substituted by halo or heteroaryl.6. The compound of claim 5 , wherein Rand Rare both methyl claim 5 , R claim 5 , R claim 5 , and Rare all hydrogen claim 5 , X is —C(O)O— claim 5 , Y is methylene claim 5 , and Z is 2-bromophenyl claim 5 , namely 2-bromobenzyl 2 claim 5 ,4-dimethylquinoline-3-carboxylate.7. The compound of claim 5 , wherein Ris methyl claim 5 , Ris phenyl claim 5 , R claim 5 , R claim 5 , and Rare all hydrogen claim 5 , X is —C(O)O— claim 5 , Y is methylene claim 5 , and Z is phenyl claim 5 , namely benzyl 2-methyl-4-phenylquinoline-3-carboxylate.8. The compound of claim 5 , wherein Rand Rare both methyl claim 5 , R claim 5 , R claim 5 , and Rare all hydrogen claim 5 , X is —C(O)O— claim 5 , Y is methylene claim 5 , and Z is 4-chlorophenyl claim 5 , namely 4-chlorobenzyl 2 claim 5 ,4-dimethylquinoline-3-carboxylate.9. The compound of claim 5 , wherein Rand Rare both methyl claim 5 , R claim 5 , R claim 5 , and Rare all hydrogen claim 5 , X is a covalent bond claim 5 , Y is 1 claim 5 ,3 claim 5 ,4-oxadiazole claim 5 , and Z is (4-chlorophenyl)propan-2-yl) claim 5 , namely 2-(2-(4-chlorophenyl)propan-2-yl)-5-(2 claim 5 ,4-dimethylquinolin-3-yl)-1 claim 5 ,3 claim 5 ,4-oxadiazole.10. The compound of claim 5 , wherein Ris methyl claim 5 , Ris phenyl claim 5 , Rand Rare hydrogen claim 5 , Ris 6-chloro claim 5 , X is —C(O)O— claim 5 , Y is methylene claim 5 , and Z is cyclopropyl claim 5 , namely ...

ANTIMICROBIAL AGENTS

The invention provides a compound of formula I:or a salt thereof, wherein R-Rand X and Y have any of the values described in the specification, as well as compositions comprising a compound of formula I. The compounds are useful as antibacterial agents. 2. The compound of wherein:{'sup': 1', 'y', 'y, 'sub': 1', '6, 'Ris Ror (C-C)alkyl that is substituted with one or more R;'}{'sup': 2', 'z', 'x, 'sub': 1', '6, 'Ris Ror (C-C)alkyl that is substituted with one or more R;'}{'sup': 4', '5', '6', '7', 'd', '4', '5', '6', '7', 'p', 'p', 'p', 'g', 'h', 'g', 'h', 'a', '4', '5', '6', '7', 'b, 'sub': 1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '3', '2', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'at least one of RRRand Ris aryl or heteroaryl wherein each aryl or heteroaryl is optionally substituted with one or more (e.g. 1, 2, 3, or 4) R; and the remainder of RRRand Rare each independently H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl, trifluoromethoxy, (C-C)alkyl, (C-C)cycloalkyl, (C-C)alkoxy, (C-C)alkoxycarbonyl, (C-C)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, (C-C)alkylthio, —S(O)R, —S(O)R, —S(O)R, —S(O)NRR, and —NRR; wherein any alkyl and any alkyl or alkanoyl portion of any aryl(C-C)alkyl, heteroaryl(C-C)alkyl, aryl(C-C)alkanoyl or heteroaryl(C-C)alkanoyl is optionally substituted with one or more (e.g. 1, 2, 3, or 4) R; and wherein any aryl, heteroaryl, or any aryl or heteroaryl portion of any aryl(C-C)alkyl, heteroaryl(C-C)alkyl, aryl(C-C)alkanoyl or heteroaryl(C-C)alkanoyl of RRRand Ris optionally substituted with one or more (e.g. 1, 2, 3, or 4) R;'}{'sup': 8', 'p', 'p', 'p', 'g', 'h', 'g', 'h', '8', 'a', '8', 'b, 'sub': 1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '3', '2, 'Ris H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl, trifluoromethoxy, (C-C)alkyl, (C-C)cycloalkyl, (C-C)alkoxy, (C-C)alkoxycarbonyl, (C-C)alkanoyloxy, aryl, heteroaryl, aryloxy, ...

FLUORESCENT DYES

The present invention provides dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins, nucleic acids and cellular organelles. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes provided in this invention can comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been substituted with specific groups to provide beneficial properties. 130-. (canceled)34. A method of identifying a specific organelle or region in a cell of interest , the method comprising{'claim-ref': {'@idref': 'CLM-00037', 'claim 37'}, '(a) incubating the cell of interest with the compound of , and'}(b) identifying the location of the organelle or region in the cell of interest by identifying the compound that stains the organelle or region.37. A target molecule comprising the compound of .38. The target molecule of claim 37 , wherein the target molecule is a nucleoside claim 37 , a nucleotide claim 37 , an oligonucleotide claim 37 , a polynucleotide claim 37 , a peptide nucleic acid claim 37 , a protein claim 37 , an oligopeptide claim 37 , an enzyme claim 37 , an antibody claim 37 , a cytokine claim 37 , avidin claim 37 , streptavidin claim 37 , digoxigenin claim 37 , an oligosaccharide claim 37 , a polysaccharide claim 37 , a lipid claim 37 , a liposome claim 37 , a glycolipid claim 37 , or a dye.39. The target molecule of claim 37 , wherein the target molecule is a protein claim 37 , an oligopeptide claim 37 , a nucleotide claim 37 , an oligonucleotide claim 37 , or a polynucleotide.41. The compound of claim 40 , wherein said reactive group comprises a nucleophilic reactive group claim 40 , an electrophilic reactive group claim 40 , a terminal alkene claim 40 , a terminal alkyne claim 40 , a coordinate group or an alkylating agent.42. The ...

METHOD OF PREVENTING OR TREATING VIRAL INFECTION

Disclosed are compounds and pharmaceutical compositions containing compounds that inhibit JMJD2 proteins, including those of the formula (I): 2. The method of claim 1 , wherein for the compound of formula (I) claim 1 ,{'sup': 1', '2, 'sub': 1', '6, 'Rand Rare each independently H or C-Calkyl;'}{'sup': '3', 'claim-text': {'sub': '2', 'claim-text': [{'sub': 1', '6', '2', 'm', '6', '20', '2', 'n', '2', '2', 'q', '2, 'L is C-Calkylenyl, (CH)—(C-Caryl)-(CH), or (CHCHO)CH, wherein m and n are each independently 0 to 6 and q is 1 to 6, and'}, {'sup': '6', 'claim-text': [{'sup': 6', '7', '7', '7, 'wherein Ris NRRor OR, and'}, {'sup': '7', 'sub': '3', 'each Ris independently H or CH;'}], 'W is R,'}], 'wherein Y is linked to N and is CH, C═O, or NH,'}, 'Ris H or a group of the formula: —Y-L-W'}{'sup': 4', '5, 'sub': 1', '6, 'Rand Rare each independently H or C-Calkyl; and'}X is O.5. The method of claim 1 , wherein the compound is any one compound listed in Tables 2-4.6. The method of claim 1 , wherein the siRNA is any one of SEQ ID NOS: 1-4.7. The method of claim 1 , wherein the viral infection involves reactivation of a virus after latency in the host.8. The method of claim 1 , wherein the viral infection is due to a herpesvirus.9. The method of claim 1 , wherein the method further comprises administering to the host an inhibitor of the LSD 1 protein.10. The method of claim 9 , wherein the inhibitor of the LSD 1 protein is a monoamine oxidase inhibitor or an RNAi molecule.11. The method of claim 10 , wherein the monoamine oxidase inhibitor is pargyline or tranylcypromine.13. The method of claim 12 , wherein for the compound of formula (I) claim 12 ,{'sup': 1', '2, 'sub': 1', '6, 'Rand Rare each independently H or C-Calkyl;'}{'sup': '3', 'claim-text': {'sub': '2', 'claim-text': [{'sub': 1', '6', '2', 'm', '6', '20', '2', 'n', '2', '2', 'q', '2, 'L is C-Calkylenyl, (CH)—(C-Caryl)-(CH), or (CHCHO)CH, wherein m and n are each independently 0 to 6 and q is 1 to 6, and'}, {'sup': ...

NOVEL TRPV3 MODULATORS

Disclosed herein are modulators of TRPV3 of formula (II): 2. The compound according to claim 1 , or a salt thereof claim 1 , wherein u is 0.3. The compound according to claim 2 , or a salt thereof claim 2 , wherein:{'sup': '1', 'Gis optionally substituted heteroaryl or optionally substituted cycloalkyl;'}{'sup': 2', '2d, 'Gis G; and'}{'sup': '2d', 'Gis optionally substituted aryl or optionally substituted heteroaryl.'}4. The compound according to claim 2 , or a salt thereof claim 2 , wherein:{'sup': '1', 'Gis optionally substituted pyridinyl, pyrimidinyl, thiazolyl, oxazolyl, or pyrazolyl;'}{'sup': 2', '2d, 'Gis G; and'}{'sup': '2d', 'Gis optionally substituted phenyl or optionally substituted pyridinyl.'}5. The compound according to claim 2 , or a salt thereof claim 2 , wherein:{'sup': 1', 'gc, 'sub': 1', '6', '1', '6', '2, 'Gis pyridinyl or pyrimidinyl; each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C-C-alkyl, C-C-haloalkyl, and N(R);'}{'sup': 'gc', 'sub': 1', '6, 'Ris hydrogen or C-C-alkyl;'}{'sup': 2', '2d, 'Gis G;'}{'sup': 2d', 'f, 'sub': 1', '6', '1', '6, 'Gis phenyl, pyridinyl, or pyrimidinyl; each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, —CN, C-C-alkyl, C-C-haloalkyl, and —OR; and'}{'sup': 'f', 'sub': 1', '6', '1', '6, 'Ris C-C-alkyl or C-C-haloalkyl.'}6. The compound according to claim 2 , or a salt thereof claim 2 , wherein:{'sup': 1', 'gc, 'sub': 1', '4', '1', '4', '2, 'Gis pyridinyl which is optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen, C-C-alkyl, C-C-haloalkyl, and N(R);'}{'sup': 'gc', 'sub': 1', '4, 'Ris hydrogen or C-C-alkyl;'}{'sup': 2', '2d, 'Gis G;'}{'sup': 2d', 'f, 'sub': 1', '4', '1', '4, 'Gis phenyl or pyridinyl; each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group ...

NOVEL BENZENESULFONAMIDE COMPOUNDS, METHOD FOR SYNTHESIZING SAME, AND USE THEREOF IN MEDICINE AS WELL AS IN COSMETICS

Benzenesulfonamide compounds having a structure of formula (I) are described. Also described, are methods for synthesizing the compounds and to the use thereof in pharmaceutical compositions for human or veterinary medicine and in cosmetic compositions. 1. A compound having the name (S)—N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonylamino]-2-[4-(propane-2-sulfonyl)piperazin-1-yl]propionamide.2. A composition comprising the compound as claimed in claim 1 , and an acceptable carrier.3. A pharmaceutical composition comprising the compound claim 1 , as claimed in and a pharmaceutically acceptable carrier.5. The compound as claimed in claim 4 , in which{'sub': '4', 'Ris an alkyl radical containing 1 to 4 carbon atoms; and'}{'sub': '3', 'Ris a polycyclic aromatic heterocylic radical containing the heteroatom N;'}and salts thereof, and enantiomers thereof.6. The compound as claimed in claim 4 , wherein the compound is (S)—N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonylamino]-2-[4-(propane-2-sulfonyl)piperazin-1-yl]propionamide claim 4 , and salts thereof claim 4 , and enantiomers thereof.7. A composition comprising the compound as claimed in claim 4 , or a salt thereof claim 4 , or an enantiomer thereof claim 4 , and an acceptable carrier.8. A pharmaceutical composition comprising the compound as claimed in claim 4 , a salt thereof claim 4 , or an enantiomer thereof claim 4 , and a pharmaceutically acceptable carrier.9. A method of treating an inflammatory skin disease claim 3 , wherein the method comprises administering the pharmaceutical composition as claimed in claim 3 , to a subject in need thereof.10. The method of claim 9 , wherein the inflammatory skin disease is psoriasis or atopic dermatitis.11. A method of treating an inflammatory skin disease claim 8 , wherein the method comprises administering the pharmaceutical composition as claimed in claim 8 , to a subject in need thereof.12. The method of claim 11 , wherein the inflammatory skin ...

NOVEL MONTELUKAST 4-HALOBENZYLAMINE SALT AND METHOD FOR PREPARING MONTELUKAST SODIUM SALT BY USING THE SAME

Disclosed are a novel montelukast 4-halobenzylamine salt, and a method for preparing a montelukast sodium salt by using the same. In the disclosed method, a montelukast 4-halobenzylamine salt represented by Formula 2 or a montelukast sodium salt represented by Formula 1 is prepared by obtaining a compound represented by Formula 3 from a compound represented by Formula 5, in the same reactor, without an additional obtaining process. 4. The method as claimed in claim 3 , wherein step a) is to obtain the compound represented by Formula 3 by reacting the compound represented by Formula 5 with methanesulfonyl chloride claim 3 , then with the compound represented by Formula 4 claim 3 , followed by the base treatment claim 3 , without an additional obtaining process.5. The method as claimed in claim 3 , wherein in step a) claim 3 , the reaction with the compound represented by Formula 4 is carried out in at least one base selected from the group consisting of cesium carbonate claim 3 , lithium hydroxide claim 3 , sodium hydroxide claim 3 , potassium hydroxide claim 3 , potassium carbonate claim 3 , and sodium carbonate.6. The method as claimed in claim 3 , wherein in step a) claim 3 , the reaction with the compound represented by Formula 4 is carried out in cesium carbonate.7. The method as claimed in any one of to claim 3 , wherein the step of reacting the compound represented by Formula 3 with the 4-halobenzylamine is carried out in at least one solvent selected from the group consisting of ethanol claim 3 , isopropyl alcohol claim 3 , acetone claim 3 , acetonitrile claim 3 , ethyl acetate claim 3 , tetrahydrofuran claim 3 , methylene chloride claim 3 , chloroform claim 3 , toluene claim 3 , xylene claim 3 , hexane claim 3 , cyclohexane and heptane.10. The method as claimed in claim 9 , wherein step a) is to obtain the compound represented by Formula 3 by reacting the compound represented by Formula 5 with methanesulfonyl chloride claim 9 , then with the compound ...

SUBSTITUTED BENZALDEHYDE COMPOUNDS AND METHODS FOR THEIR USE IN INCREASING TISSUE OXYGENATION

Provided are substituted benzaldehydes and derivatives thereof that act as allosteric modulators of hemoglobin, methods and intermediates for their preparation, pharmaceutical compositions comprising the modulators, and methods for their use in treating disorders mediate by hemoglobin and disorders that would benefit from increased tissue oxygenation. 2. A compound according to claim 1 , wherein:{'sub': '2', 'Y is O or CH;'}{'sub': '2', 'X is O or CH;'}Q is selected from the group consisting of:{'sup': 'a', 'claim-text': {'sup': 2', '3', '4', '5', 'b', 'd', 'd', 'd', 'd', 'e', 'd', 'd', 'd', 'd', 'd', 'd', 'd', 'd', 'd', 'd', 'e', 'd', 'e', 'd', 'd', 'd', 'e', 'e', 'd', 'e', 'd', 'd, 'sub': 2', 'z', '2', 'z', '2', '2', '2', '2', '2', '2', '3, 'R, R, R, and R, are independently selected from the group consisting of hydrogen, halo, R, OR, O(CH)OR, O(CH)NRR, OC(O)R, SR, CN, NO, COR, CONRR, C(O)R, OC(O)NRR, NRR, NRC(O)R, NRC(O)R, NRC(O)NRR, S(O)R, S(O)R, NRS(O)R, S(O)NRR, and Nwhere z is 1, 2, or 3; and'}, 'i) imidazopyridinyl, methylimidazopyridinyl, indazolyl, pyrrolopyridinyl, pyrrolopyrazinyl, pyrazolopyridinyl, pyrazolopyrazinyl, and quinolinyl, each of which is optionally substituted with one to three R; wherein'}{'sup': 'a', 'claim-text': [{'sup': 2', '3', '4', 'b', 'd', 'd', 'd', 'd', 'e', 'd', 'd', 'd', 'd', 'd', 'd', 'd', 'd', 'd', 'd', 'e', 'd', 'e', 'd', 'd', 'd', 'e', 'e', 'd', 'e', 'd', 'd, 'sub': 2', 'z', '2', 'z', '2', '2', '2', '2', '2', '2', '3, 'R, R, and Rare independently selected from the group consisting of hydrogen, halo, R, OR, O(CH)OR, O(CH)NRR, OC(O)R, SR, CN, NO, COR, CONRR, C(O)R, OC(O)NRR, NRR, NRC(O)R, NRC(O)R, NRC(O)NRR, S(O)R, S(O)R, NRS(O)R, S(O)NRR, and Nwhere z is 1, 2, or 3; and'}, {'sup': 5', 'd, 'Ris selected from the group consisting of halo and OR;'}], 'ii) pyridinyl and piperidinyl, each of which is optionally substituted with one to three R; wherein'}{'sup': 6', '7, 'Rand Rtogether form oxo or an aldehyde protecting group;'}{' ...

INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

Compounds of formula I: 238.-. (canceled) This application claims benefit of U.S. Ser. No. 60/988,686, filed Nov. 16, 2007, which is herein incorporated by reference.The present invention relates to compounds, compositions and methods for the treatment of human immunodeficiency virus (HIV) infection. In particular, the present invention provides novel inhibitors of HIV replication, pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HIV infection. More specifically, the present invention provides novel inhibitors of the HIV integrase enzyme, pharmaceutical compositions containing such compounds and methods for using these compounds to reduce HIV replication and in the treatment of HIV infection.Acquired immune deficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV), particularly the HIV-1 strain. Most currently approved therapies for HIV infection target the viral reverse transcriptase and protease enzymes. There is additionally one approved drug targeting gp41 to inhibit viral entry and one approved drug targeting the integrase enzyme. Within the reverse transcriptase inhibitor and protease inhibitor classes, resistance of HIV to existing drugs is a problem. Therefore, it is important to discover and develop new antiretroviral compounds.The inherent genetic variation within HIV has led to the identification of many HIV mutants, commonly referred to as variants, which exhibit altered drug susceptibility. On the integrase enzyme, residues 124 and 125 are recognized as highly variable across the HIV-1 virus from infected patients found in major market and developing countries. The approximate prevalence of these integrase variants are Thr124/Thr125 (44%), Ala124/Thr125 (17%), Ala124/Ala125 (16%), Thr124/Ala125 (10%), Asn124/Thr125 (6%), and Asn124/Ala125 (1%) for viruses sequenced from major market countries reported in the Los Alamos database (http://www.hiv.lanl.gov/content/hiv-db). ...

NAPHT-2-YLACETIC ACID DERIVATIVES TO TREAT AIDS

The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula (I). 2. The compound of wherein Ris (C-C)alkyl claim 1 , (C-C)alkenyl or —O(C-C)alkyl wherein any (C-C)alkyl or (C-C)alkenyl of Ris optionally substituted with one or more groups selected from —O(C-C)alkyl claim 1 , halo claim 1 , oxo and —CN; and wherein Ris H.4. The compound of wherein Ris selected from:{'sub': 1', '6', '2', '6', '1', '6', '3', '7', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6, 'a) aryl, heterocycle and heteroaryl, wherein any aryl, heterocycle and heteroaryl is optionally substituted with one or more groups each independently selected from halo, (C-C)alkyl, (C-C)alkenyl, (C-C)haloalkyl, (C-C)cycloalkyl, —OH, —O(C-C)alkyl, —SH, —S(C-C)alkyl, —NH, —NH(C-C)alkyl and —N((C-C)alkyl), wherein (C-C)alkyl is optionally substituted with hydroxy, —O(C-C)alkyl, cyano or oxo;'}{'sub': 3', '14', '3', '14', '3', '7, 'sup': 1', '1, 'b) (C-C)carbocycle, wherein (C-C)carbocycle is optionally substituted with one or more Zgroups, wherein two Zgroups together with the atom or atoms to which they are attached optionally form a (C-C)carbocycle or heterocycle; and'}{'sup': 7', '1, 'c) aryl, heteroaryl and fused-heterocycle, wherein any aryl, heteroaryl and fused-heterocycle is substituted with one or more Zgroups and optionally substituted with one or more Zgroups.'}5. The compound of wherein Ris selected from:{'sub': 1', '6', '2', '6', '1', '6', '3', '7', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6, 'a) aryl, heterocycle and heteroaryl, wherein any aryl, heterocycle and ...

CRYSTAL FORM OF QUINOLINE COMPOUND AND PROCESS FOR ITS PRODUCTION

A method for producing a drug substance of crystalline pitavastatin calcium excellent in stability, is presented. In the production of a compound (pitavastatin calcium) represented by the formula (1): 2. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 5% (w/w) or greater.3. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 5 to 15% (w/w).4. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 7% (w/w) or greater.5. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 7 to 13% (w/w).6. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 7 to 15% (w/w).7. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 9% (w/w) or greater.8. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 9 to 13% (w/w).17. The method according to claim 9 , wherein drying the crystals comprises drying under reduced pressure.18. The method according claim 9 , wherein drying the crystals comprises drying at a temperature of from 15 to 40° C.19. The method according to claim 1 , wherein maintaining the water content of the pitavastatin calcium salt comprises storing under air tight conditions.20. The method according to claim 1 , wherein the X-ray powder diffraction pattern of the pitavastatin calcium salt claim 1 , as measured using CuKα radiation claim 1 , exhibits peaks at diffraction angles (2θ) of 4.96° claim 1 , 6.72° claim 1 , 9.08° claim 1 , 10.40° claim 1 , 10.88° claim 1 , 13.20° claim 1 , 13.60° claim 1 , 13.96° claim 1 , 18.32° claim 1 , 20.68° claim 1 , 21.52° claim 1 , 23.64° claim 1 , 24.12° claim 1 , 27.00° claim 1 , and 30.16°.21. A pharmaceutical or veterinary medicine ...

2-quinolinyl-acetic acid derivatives as hiv antiviral compounds

The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula (I).

COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR

Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases. 2. The compound of claim 1 , wherein Ris hydrogen.3. The compound of claim 2 , wherein Ris halogen.4. The compound of claim 2 , wherein Ris optionally substituted phenyl.5. The compound of claim 2 , wherein Ris phenyl optionally substituted with one or more halogen substituents.6. The compound of claim 1 , wherein Ris phenyl optionally substituted with one or more fluoro substituents.7. The compound of claim 6 , wherein Ris phenyl substituted with two fluoro substituents.8. The compound of claim 1 , wherein each Ris independently optionally substituted lower alkyl or optionally substituted heteroaryl.9. The compound of claim 8 , wherein one Ris lower alkyl and the other Ris heteroaryl substituted with one or more NHgroups.10. The compound of claim 8 , wherein one Ris lower alkyl and the other Ris pyrimidinyl substituted with one or more NHgroups.11. The compound of claim 10 , wherein one Ris t-butyl and the other Ris pyrimidinyl substituted with NH.13. The compound of claim 12 , wherein Ar is thiazolyl.14. The compound of claim 12 , wherein Ar is 4-thiazolyl.16. A pharmaceutical composition comprising: a compound of and a pharmaceutically acceptable carrier or excipient.17. A pharmaceutical composition comprising: a compound of and a pharmaceutically acceptable carrier or excipient.18. A pharmaceutical composition comprising a compound of and another therapeutic agent.19. A method for treating a subject suffering from melanoma claim 15 , thyroid cancer or colorectal cancer claim 15 , said method comprising: administering to the subject an effective amount of a compound of .20. The method of claim 19 , wherein the melanoma is melanoma having a mutation encoding a V600E amino acid substitution. This application is a continuation application of U.S. application Ser. No. 12/669,450, filed Jan ...

DIARYLACETYLENE HYDRAZIDE CONTAINING TYROSINE KINASE INHIBITORS

The present invention relates to novel diarylacetylene hydrazide compounds of formula (I) or pharmaceutically acceptable salt thereof, as tyrosine kinase inhibitors, the process for their preparation, and to the use of the compounds of formula (I) in the preparation of pharmaceutical compositions for the therapeutic treatment of disorders related to tyrosine kinases, in warm-blooded animals

INHIBITOR COMPOUNDS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1

The compounds of formula (I) are derived from perhydroquinoline and perhydroisoquinoline and are useful as active pharmaceutical ingredients for the prophylaxis or treatment of diseases caused by 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-HSD1) enzyme-associated disorders, such as glaucoma, elevated ocular pressure, metabolic disorders, obesity, metabolic syndrome, dyslipidemia, hypertension, diabetes, atherosclerosis, Cushing's syndrome, psoriasis, rheumatoid arthritis, cognitive disorders, Alzheimer's disease or neurodegeneration. 2. The method according to claim 1 , wherein in the compound Y is CO or SO.3. The method according to claim 1 , wherein in the compound W1 and W2 is each independently selected from the group consisting of a bond claim 1 , S and NR1.4. The method according to claim 3 , wherein in the compound R1 is H5. The method according to claim 1 , wherein in the compound V is —CO-T claim 1 , —CS-T or —SO-T.7. The method according to claim 1 , wherein in the compound T is NR2R3 claim 1 , R2 claim 1 , OR2 or SR2.8. The method according to claim 1 , wherein in the compound R2 and R3 is each independently selected from the group consisting of H claim 1 , COR4 claim 1 , SOR4 claim 1 , Calkyl claim 1 , phenyl claim 1 , naphthyl claim 1 , benzyl claim 1 , phenethyl claim 1 , Calkenyl claim 1 , Ccycloalkyl claim 1 , and heterocycle claim 1 , particularly claim 1 , 2-furanyl claim 1 , 2-thiophenyl claim 1 , 2-(1-methylindole) claim 1 , quinoline claim 1 , isoquinoline and 2-benzofuranyl.9. The method according to claim 8 , wherein in the compound R2 and R3 is each independently selected from the groups consisting of Calkyl and Calkenyl.10. The method according to claim 9 , wherein in the compound R2 or R3 are optionally substituted with one or several substituents independently selected from the groups consisting of F claim 9 , OR4 claim 9 , NR4R5 claim 9 , COOR4 claim 9 , CONR4R5 claim 9 , phenyl claim 9 , Ccycloalkyl claim 9 , hexenyl claim 9 , ...

Indanyloxyphenylcyclopropanecarboxylic acids

The present invention relates to compounds of general formula I, wherein the groups R 1 , R 2 , R 3 , m and n are defined as in claim 1 , which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2. Furthermore, the invention relates to novel intermediates, useful for the synthesis of compounds of formula I.

TAU IMAGING PROBE

An object of the present invention is to provide a probe for imaging a β-sheet structure protein which can be used for the diagnosis of conformational diseases, particularly disease (tauopathy) having a cardinal symptom such as intracerebral accumulation of tau protein, for example, Alzheimer's disease. Another object of the present invention is to provide a compound which is highly specific to tau and can image tau with satisfactory sensitivity, and also has high brain transition, low or non-recognized bone-seeking properties and low or non-recognized toxicity. 143-. (canceled)47. The compound according to claim 44 , wherein at least one of R claim 44 , Rand Ris NRR claim 44 , and Rand Reach independently represents hydrogen or an unsubstituted lower alkyl group claim 44 , or a pharmaceutically acceptable salt or solvate thereof.48. The compound according to claim 44 , wherein the compound is labeled claim 44 , or a pharmaceutically acceptable salt or solvate thereof.49. A pharmaceutical composition comprising the compound according to claim 44 , or a pharmaceutically acceptable salt or solvate thereof.50. A composition for the diagnosis claim 44 , treatment and/or prevention of conformational disease claim 44 , comprising the compound according to claim 44 , or a pharmaceutically acceptable salt or solvate thereof.51. A kit for the diagnosis of conformational disease claim 44 , or detecting or staining a beta-sheet structure protein comprising the compound according to claim 44 , or a pharmaceutically acceptable salt or solvate thereof as an essential ingredient.52. A method of treating and/or preventing conformational disease claim 44 , or diagnosing a conformational disease in a subject claim 44 , which comprises administering the compound according to claim 44 , or a pharmaceutically acceptable salt or solvate thereof to the subject.53. A method of detecting or staining a β-sheet structure protein in a sample claim 44 , which comprises staining the sample using ...

PROCESS AND INTERMEDIATE COMPOUNDS USEFUL IN THE PREPARATION OF STATINS

There is provides a process for the preparation of a compound of formula (7): wherein R is an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; provides that R is not a compound of Formula (a): wherein Rrepresents an alkyl group, such as a Calkyl group, and preferably an isopropyl group; Rrepresents an aryl group, preferably a 4-fluorophenyl group; Rrepresents hydrogen, a protecting group or an alkyl group, such as a Calkyl group, and preferably a methyl group; and Rd represents hydrogen, a protecting group or a SORgroup where Ris an alkyl group, such as a Calkyl group, and preferably a methyl group. 17-. (canceled)9. The process of wherein Y is Cl or Br.11. The process of claim 10 , wherein Ris an alkyl group and/or Ris an alkanoyl group.12. The process of claim 11 , wherein Ris a Calkyl group and/or Ris a Calkanoyl group.13. The process of claim 12 , wherein Ris a —C(O)CH(Me)CHCHor —C(O)C(Me)CHCHgroup14. The process of claim 10 , wherein Ris an alkanoyl group.15. The process of claim 14 , wherein Ris a Calkanoyl group16. The process of claim 14 , wherein Ris a —C(O)CH(Me)CHCHor a —C(O)C(Me)CHCHgroup.17. The process of claim 10 , wherein Ris a substituted or unsubstituted aryl group and/or Ris a substituted or unsubstituted alkyl group.18. The process of claim 17 , wherein Ris a 4-fluorophenyl group and/or Ris a cyclopropyl group.19. The process of claim 10 , wherein Ris a substituted or unsubstituted aryl group and/or Ris a substituted or unsubstituted alkyl group.20. The process of claim 19 , wherein Ris a 4-fluorophenyl group and/or Ris an isopropyl group.21. The process of claim 10 , wherein Ris a substituted or unsubstituted aryl or a substituted or unsubstituted aromatic heterocyclic group; Ris a substituted or unsubstituted aryl group; and/or Ris a substituted or unsubstituted aryl group.22. The process of claim 21 , wherein Ris a methyltetrazoyl group; Ris a 4-fluorophenyl group; and/or Ris a 4-fluorophenyl group.23. ...

Crystalline forms of pitavastatin calcium

The present invention is directed to new crystalline forms of Pitavastatin hemicalcium salt, referred to hereinafter as polymorphic Forms A, B, C, D, E and F, as well as the amorphous form. Furthermore, the present invention is directed to processes for the preparation of these crystalline forms and the amorphous form and pharmaceutical compositions comprising these crystalline forms or the amorphous forms.

New palladium catalyst, method for its preparation and its use

The invention relates to palladium(0) tris{tri-[3,5-bis(trifluoromethyl)-phenyl]-phosphine} complex of formula (I), as well as to its preparation and use. This compound is outstandingly stable, and can be used as catalyst with excellent results.

Compounds and methods for kinase modulation, and indications therefor

Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS

Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same. 1. (canceled)3. The method of wherein the neurological disorder is selected from the group consisting of psychotic disorders claim 2 , anxiety disorders claim 2 , movement disorders and/or neurological disorders such as Parkinson's disease claim 2 , Huntington's disease claim 2 , Alzheimer's disease claim 2 , encephalitis claim 2 , phobias claim 2 , epilepsy claim 2 , aphasia claim 2 , Bell's palsy claim 2 , cerebral palsy claim 2 , sleep disorders claim 2 , pain claim 2 , Tourette's syndrome claim 2 , schizophrenia claim 2 , delusional disorders claim 2 , bipolar disorders claim 2 , post-traumatic stress disorders claim 2 , drug-induced psychosis claim 2 , panic disorders claim 2 , obsessive-compulsive disorders claim 2 , attention-deficit disorders claim 2 , disruptive behavior disorders claim 2 , autism claim 2 , depression claim 2 , dementia claim 2 , cognitive disorders claim 2 , epilepsy claim 2 , insomnias and multiple sclerosis.4. The method of wherein the neurological disorder is schizophrenia.5. The method of wherein the neurological disorder is post-traumatic stress disorder.7. The method of wherein Rand Rare the same or different and ...

Process for the preparation of key intermediates for the synthesis of statins or pharmaceutically acceptable salts thereof

The invention relates to commercially viable process for the synthesis of key intermediates for the preparation of statins, in particular Rosuvastatin and Pitavastatin or respective pharmaceutically acceptable salts thereof. A new simple and short synthetic route for key intermediates is presented which benefits from the use of cheap and readily available starting materials, by which the conventionally most frequently used DIBAL-H as reducing agent can be avoided.

CRYSTAL FORM OF QUINOLINE COMPOUND AND PROCESS FOR ITS PRODUCTION

A method for producing a drug substance of crystalline pitavastatin calcium excellent in stability, is presented. In the production of a compound (pitavastatin calcium) represented by the formula (): 3. A method for producing a drug substance of the crystal (crystal form A) as defined in claim 1 , which comprises adjusting the water content to a level of from 5 to 15%.4. A pharmaceutical composition which contains the crystal (crystal form A) as defined in .5. The crystal (crystal form A) as defined in claim 1 , wherein the crystal has an X-ray powder diffraction pattern as shown in . This application is a continuation of U.S. patent application Ser. No. 13/487,289, filed Jun. 4, 2012, which is a continuation of U.S. patent application Ser. No. 13/227,003, filed Sep. 7, 2011, which is a continuation of U.S. patent application Ser. No. 12/966,102, filed Dec. 13, 2010, which is a continuation of U.S. patent application Ser. No. 12/401,945, filed Mar. 11, 2009, which is a continuation of U.S. patent application Ser. No. 10/584,208, filed Jun. 23, 2006, which is the U.S. National Stage of International Application No. PCT/JP04/019451, filed Dec. 17, 2004, the disclosures of which are incorporated herein by reference in their entireties. This application claims priority to Japanese Patent Application No. 2003-431788, filed Dec. 26, 2003, the disclosure of which is incorporated herein by reference in its entirety.The present invention relates to a crystal form of pitavastatin calcium known by a chemical name monocalcium bis[(3R,5S,6E)-7-(2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl)-3,5-dihydroxy-6-heptenoate], which is useful for treatment of hyperlipemia, as a HMG-COA reductase inhibitor, a process for its production, and a pharmaceutical composition comprising this compound and a pharmaceutically acceptable carrier.Particularly, it relates to pitavastatin calcium in a crystal form, which is characterized by containing from 5 to 15% (W/W) of water and which is useful as ...

PROCESS FOR THE PREPARATION OF AN HIV INTEGRASE INHIBITOR

The present invention is directed to an improved process for the preparation of Compounds of Formula (I), which are useful in the treatment of HIV infection. In particular, the present invention is directed to an improved process for the preparation of (2S)-2-tert-butoxy-2-(4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-2-methylquinolin-3-yl)acetic acid, which is useful in the treatment of HIV infection. 2. The process according to claim 1 , wherein the palladium catalyst or precatalyst is [Pd(allyl)Cl].5. The process according to claim 1 , wherein the chiral alcohol F1 is converted to tert-butyl ether G1 using trifluoromethanesulfonimide as the catalyst and t-butyl-trichloroacetimidate as source tert-butyl cation.7. The process according to claim 6 , wherein the palladium catalyst or precatalyst is [Pd(allyl)Cl].10. The process according to claim 6 , wherein the chiral alcohol F1 is converted to tert-butyl ether G1 with trifluoromethanesulfonimide as the catalyst and t-butyl-trichloroacetimidate.12. The process according to claim 11 , wherein the palladium catalyst or precatalyst is [Pd(allyl)Cl].13. The process according to claim 11 , wherein the chiral alcohol F is converted to tert-butyl ether G with trifluoromethanesulfonimide as the catalyst and t-butyl-trichloroacetimidate.15. The process according to claim 14 , wherein the palladium catalyst or precatalyst is [Pd(allyl)Cl].17. The process according to claim 14 , wherein the chiral alcohol F is converted to tert-butyl ether G with trifluoromethanesulfonimide as the catalyst and t-butyl-trichloroacetimidate.18. The process according to claim 4 , wherein the halide X in compound O is converted to the corresponding boronic acid P claim 4 , in the presence of toluene.20. The process according to claim 9 , wherein the halide X in compound O is converted to the corresponding boronic acid P claim 9 , in the presence of toluene. This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent ...

PROCESS FOR THE PREPARATION OF AN HIV INTEGRASE INHIBITOR

The present invention is directed to an improved process for the preparation of Compounds of Formula (I) or salts thereof which are useful in the treatment of HIV infection. In particular, the present invention is directed to an improved process for the preparation of (2S)-2-tert-butoxy-2-(4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-2-methylquinolin-3-yl)acetic acid or salt thereof which is useful in the treatment of HIV infection. 5. The process according to claim 1 , wherein the chiral alcohol F1 is converted to tert-butyl ether G1 using trifluoromethanesulfonimide as the catalyst and t-butyl-trichloroacetimidate as source tert-butyl cation.7. The process according to claim 6 , wherein the palladium catalyst or precatalyst is tris(dibenzylideneacetone)dipalladium(0).11. The process according to claim 6 , wherein the chiral alcohol F1 is converted to tert-butyl ether G1 with trifluoromethanesulfonimide as the catalyst and t-butyl-trichloroacetimidate.14. The process according to claim 12 , wherein the chiral alcohol F is converted to tert-butyl ether G with trifluoromethanesulfonimide as the catalyst and t-butyl-trichloroacetimidate.16. The process according to claim 15 , wherein the palladium catalyst or precatalyst is tris(dibenzylideneacetone)dipalladium(0).18. The process according to claim 15 , wherein the chiral alcohol F is converted to tert-butyl ether G with trifluoromethanesulfonimide as the catalyst and t-butyl-trichloroacetimidate.19. The process according to claim 4 , wherein the halide X in compound O is converted to the corresponding boronic acid P claim 4 , in the presence of toluene.21. The process according to claim 9 , wherein the halide X in compound O is converted to the corresponding boronic acid P claim 9 , in the presence of toluene. This application is a continuation of International PCT Patent Application No. PCT/US2012/032027, filed Apr. 3, 2012, now pending, which claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent ...

Monomer for hardmask composition and hardmask composition including the monomer and method of forming patterns using the hardmask composition

A monomer for a hardmask composition is represented by the following Chemical Formula 1,

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 0.10. 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 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 ...

IMMUNOREGULATORY AGENTS

Compounds that modulate the oxidoreductase enzyme indoleamine 2,3-dioxygenase, and compositions containing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by indoleamine 2,3-dioxygenase is also provided. 1. A compound having the formula (I): the subscript n is 1; the subscript p is 1;', {'sub': '5', 'the ring designated as A is phenyl, 5- or 6-membered heteroaryl, or C-7 cycloalkyl;'}, 'Z is O;', {'sup': '3a', 'B is C(R);'}, {'sup': 5', '5a, 'each X is independently, CHR, C(O), or CH(OR);'}, {'sup': '6', 'Q is N, C(CN), or CR;'}, {'sup': 5', '5a, 'sub': '2', 'D is a bond, O, C(R), or NR;'}, 'E is a substituted 9- or 10-membered fused bicyclic heteroaryl, optionally substituted with halogen;', {'sup': 1', '2, 'Rand Rare independently hydrogen or halogen;'}, {'sup': 3', '3a', '4, 'sub': 1', '6, 'R, Rand Rare independently hydrogen or C-Calkyl;'}, {'sup': '5', 'sub': 1', '6, 'each Ris independently H, F, OH, or C-Calkyl;'}, {'sup': '5a', 'sub': 1', '6, 'each Ris independently H, or C-Calkyl;'}, {'sup': '6', 'sub': 1', '6', '1', '6', '5a', '2, 'Ris H, OH, F, C-Calkyl, —O—C-Calkyl, or —N(R);'}, 'and each m is independently 1, 2, or 3., 'or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein,'}2. A combination comprising a compound of or a pharmaceutically acceptable salt claim 1 , hydrate or solvate thereof claim 1 , and at least one additional therapeutic agent.3. The combination of claim 2 , wherein said additional therapeutic agent is an immuno-oncology agent.4. The combination of claim 3 , wherein said immuno-oncology agent is selected from a CTLA-4 antagonist claim 3 , a PD-1 antagonist claim 3 , a PD-L1 antagonist claim 3 , a LAG-3 antagonist claim 3 , a CD137 agonist claim 3 , a GITR agonist claim 3 , an OX40 agonist claim 3 , an OX40L antagonist claim 3 , ...

Crystalline forms of pitavastatin calcium

The present invention is directed to new crystalline forms of Pitavastatin hemicalcium salt, referred to hereinafter as polymorphic Forms A, B, C, D, E and F, as well as the amorphous form. Furthermore, the present invention is directed to processes for the preparation of these crystalline forms and the amorphous form and pharmaceutical compositions comprising these crystalline forms or the amorphous forms.

TLR7/8 ANTAGONISTS AND USES THEREOF

A method of administering to a patient in need thereof or contacting with a biological sample, a compound related to Formula I 116-. (canceled)19. The method of claim 18 , wherein the disorder is selected from Rheumatoid Arthritis claim 18 , Psoriatic arthritis claim 18 , Osteoarthritis claim 18 , Systemic Lupus Erythematosus claim 18 , Lupus nephritis claim 18 , Ankylosing Spondylitis claim 18 , Osteoporosis claim 18 , Systemic sclerosis claim 18 , Multiple Sclerosis claim 18 , Psoriasis claim 18 , Type I diabetes claim 18 , Type II diabetes claim 18 , Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis) claim 18 , Hyperimmunoglobulinemia D and periodic fever syndrome claim 18 , Cryopyrin-associated periodic syndromes claim 18 , Schnitzler's syndrome claim 18 , Systemic juvenile idiopathic arthritis claim 18 , Adult's onset Still's disease claim 18 , Gout claim 18 , Pseudogout claim 18 , SAPHO syndrome claim 18 , Castleman's disease claim 18 , Sepsis claim 18 , Stroke claim 18 , Atherosclerosis claim 18 , Celiac disease claim 18 , DIRA (Deficiency of IL-1 Receptor Antagonist) claim 18 , Alzheimer's disease claim 18 , Parkinson's disease claim 18 , Sjorgen's disease claim 18 , polymyositis claim 18 , dermatomyositis claim 18 , and Cancer.21. The method of claim 17 , wherein Ris —H claim 17 , —R claim 17 , halogen claim 17 , -haloalkyl claim 17 , —OR claim 17 , —CN claim 17 , or —N(R).23. The method of claim 17 , wherein each R is independently Caliphatic claim 17 , Caryl claim 17 , a 3-8 membered saturated or partially unsaturated carbocyclic ring claim 17 , a 3-7 membered heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen claim 17 , oxygen claim 17 , or sulfur claim 17 , or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen claim 17 , oxygen claim 17 , or sulfur; each of which is optionally substituted.24. The method of claim 23 , wherein each Ris independently methyl claim ...

TLR7/8 ANTAGONISTS AND USES THEREOF

A compound of Formula I 2. The compound of claim 1 , wherein Ring A is Caryl or a 6 membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.3. The compound of claim 2 , wherein Ring A is phenyl claim 2 , pyridyl claim 2 , pyrimidinyl claim 2 , pyrazinyl claim 2 , pyridazinyl claim 2 , or triazinyl.5. The compound of claim 1 , wherein Ring B is a 5-6 membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.78-. (canceled)9. The compound of claim 1 , wherein each Ris independently Caliphatic claim 1 , —C(O)R claim 1 , —C(NH)NR claim 1 , —NRC(O)R claim 1 , —N(R); or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur; each of which is optionally substituted.11. The compound of claim 1 , wherein each Ris independently Caliphatic claim 1 , Caryl claim 1 , a 3-8 membered saturated or partially unsaturated carbocyclic ring claim 1 , a 3-7 membered heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur claim 1 , or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur; each of which is optionally substituted.12. The compound of claim 11 , wherein each Ris independently methyl claim 11 , ethyl claim 11 , ethyl claim 11 , propyl claim 11 , i-propyl claim 11 , butyl claim 11 , s-butyl claim 11 , t-butyl claim 11 , straight or branched pentyl claim 11 , or straight or branched hexyl; each of which is optionally substituted.16. A pharmaceutical composition claim 11 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the compound of , and a pharmaceutically acceptable adjuvant, carrier, or vehicle.'}17. A method for inhibiting TLR7/8 claim 11 , or a mutant thereof claim 11 , activity in a patient or in ...

Retinoid derivatives with antitumor activity

The present invention relates to compounds of formula (I) and to pharmaceutical compositions containing them: wherein meanings of the substituents are indicated in the description. Such compounds for use in the treatment of cancer and other diseases related to altered angiogenesis, such as arthritic pathology, diabetic retinopathy, psoriasis and chronic inflammatory disease, are also within the scope of the present invention.

Tetrahydroquinoline Derivatives and Their Use as Epac Inhibitors

The invention relates to tetrahydroquinoline derivatives and their use in the treatment and/or the prevention of a disease wherein the Epac protein is involved, such as inflammation, cancer, vascular diseases, kidney diseases, cognitive disorders and cardiac diseases. 115-. (canceled)17. (canceled) The invention relates to tetrahydroquinoline derivatives, their use as Epac inhibitors and their pharmaceutical uses.Cyclic adenosine 3′,5′-monophosphate (cAMP) is a universal second messenger that plays a crucial role in the intracellular signal transduction of various stimuli controlling a wide variety of cellular events including secretion, cell proliferation and differentiation, migration, and apoptosis. The guanine exchange factor (GEF) Epac (Exchange Protein directly Activated by Cyclic AMP) has been shown to contribute to cAMP signalling in many processes (M. Breckler et al., Rap-linked cAMP signaling Epac proteins: compartimentation, functioning and disease implications, Cell. Signal. 23 (2011) 1257-1266).There are two isoforms of Epac, Epac1 and Epac2, both consisting of a regulatory region binding directly cAMP and a catalytic region that promotes the exchange of GDP (Guanosine diphosphate) for GTP (Guanosine-5′-triphosphate) on the Ras-like small GTPases Rap1 and Rap2 isoforms. In the absence of cAMP, the regulatory region containing the cAMP-binding domain directly interacts with the catalytic region and inhibits its GEF activity. Binding of cAMP to Epac induces large conformational changes within the protein and releases the autoinhibitory effect of the N-terminal region, leading to Rap activation.The two isoforms of Epac differ in that Epac1 has a single cyclic nucleotide-binding (CNB) domain, whereas Epac2 has two CNB domains, called CNB-A and CNB-B, which are located on both sides of the DEP domain (Dishevelled, Egl-10 and Pleckstrin domain). The additional N-terminal CNB domain in Epac2 has a low affinity for cAMP, and its deletion does not affect the ...

SUBSTITUTED CHROMANES, ANALOGS THEREOF, AND METHODS OF USE AND SYNTHESIS

Disclosed are chromane compounds, analogs thereof, and methods of their synthesis and use. The compounds may be synthesized by methods involving reductive annulations of arylidene malonates with unsaturated electrophiles using photoredox/Lewis acid cooperative catalysis. The compounds may be formulated in a pharmaceutical composition for treating one of the aforementioned diseases or disorders. 2. The compound of claim 1 , wherein Rand/or Ris carboxyalkyl.3. The compound of claim 2 , wherein the carboxyalkyl is a branched or unbranched carboxy-C-alkyl.4. The compound of claim 2 , wherein the carboxyalkyl is carboxymethyl.5. The compound of claim 2 , wherein the carboxyalkyl is carboxyethyl.6. The compound of claim 2 , wherein the carboxyalkyl is carboxyisopropyl.7. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , and Ris bromo.8. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , and Ris fluoro.9. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , and Ris chloro.10. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , and Ris a branched or unbranched C-alkyl.11. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , and Ris methyl.12. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , and Ris tert-butyl.13. The compound of claim 1 , wherein Rand Rjoin together to form an aryl group.14. The compound of claim 1 , wherein Ror Ris hydrogen.15. The compound of claim 1 , wherein Ris hydrogen and Ris selected from the group consisting of phenyl claim 1 , branched or unbranched carboxy-C-alkyl claim 1 , cyano claim 1 , and carboxyalkylaryl (e.g. claim 1 , carboxybenzyl).18. The method of claim 17 , wherein the reagents further comprise a reducing agent. This application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/871,673 filed on Jul. 8, 2019, the entire contents of which are incorporated by reference herein. ...

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 , ...

Novel glp-1 receptor modulators

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “ ” represents either or both the R and S form of the compound): where A, B, C, Y 1 , Y 2 , Z, R 1 , R 2 , R 3 , R 4 , R 5 , W 1 , n, p and q are as defined herein.

CRYSTALLINE FORMS OF PITAVASTATIN CALCIUM

The present invention is directed to new crystalline forms of Pitavastatin hemicalcium salt, referred to hereinafter as polymorphic Forms A, B, C, D, E and F, as well as the amorphous form. Furthermore, the present invention is directed to processes for the preparation of these crystalline forms and the amorphous form and pharmaceutical compositions comprising these crystalline forms or the amorphous forms. 1A) polymorph A exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 5.0 (s), 6.8 (s), 9.1 (s), 10.0 (w), 10.5 (m), 11.0 (m), 13.3 (vw), 13.7 (s), 14.0 (w), 14.7 (w), 15.9 (vw), 16.9 (w), 17.1 (vw), 18.4 (m), 19.1 (w), 20.8 (vs), 21.1 (m), 21.6 (m), 22.9 (m), 23.7 (m), 24.2 (s), 25.2 (w), 27.1 (m), 29.6 (vw), 30.2 (w), 34.0 (w);B) polymorph B exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 4.6 (w), 5.3 (vs), 6.2 (s), 7.7 (s), 9.2 (m), 9.6 (m), 10.3 (w), 11.3 (m), 11.7 (w), 12.6 (vw), 13.0 (w), 13.9 (m), 14.7 (vw), 14.9 (w), 15.6 (w), 16.3 (m), 17.0 (vw), 17.4 (vw), 18.0 (w), 18.7 (m), 19.3 (m), 20.0 (s), 20.5 (w), 20.8 (m), 21.2 (w, shoulder), 21.5 (m), 22.4 (m), 23.2 (s), 23.8 (m), 24.4 (vw), 25.2 (w, broad), 26.0 (w), 26.4 (vw), 27.0 (w), 27.9 (vw), 28.9 (w);C) polymorph C exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 4.1 (m), 5.6 (s), 7.8 (m), 8.3 (m), 10.3 (m), 11.6 (w), 17.5 (w), 17.9 (w), 18.7 (m), 19.5 (s), 20.6 (m), 21.5 (vw), 21.9 (m), 23.1 (m), 24.0 (w), 24.8 (w);D) polymorph D exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 5.0 (m), 6.5 (m), 6.8 (s), 8.7 (m), 10.0 (m), 10.2 (m), 10.8 (m), 13.1 (w), 13.5 (m), 14.3 (s), 15.3 (vw), 16.1 (m), 16.8 (w), 18.2 (w), 18.5 (m), 19.0 (w), 19.9 (m), 20.5 (m), 21.0 (vs), 21.7 (s), 22.3 (w), 23.4 (m), 24.0 (m), 25.6 (w), 26.2 (m);E) polymorph E exhibits a characteristic X-ray powder diffraction ...

CRYSTALLINE FORMS OF PITAVASTATIN CALCIUM

The present invention is directed to new crystalline forms of Pitavastatin hemicalcium salt, referred to hereinafter as polymorphic Forms A, B, C, D, E and F, as well as the amorphous form. Furthermore, the present invention is directed to processes for the preparation of these crystalline forms and the amorphous form and pharmaceutical compositions comprising these crystalline forms or the amorphous forms. 1A) polymorph A exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 5.0 (s), 6.8 (s), 9.1 (s), 10.0 (w), 10.5 (m), 11.0 (m), 13.3 (vw), 13.7 (s), 14.0 (w), 14.7 (w), 15.9 (vw), 16.9 (w), 17.1 (vw), 18.4 (m), 19.1 (w), 20.8 (vs), 21.1 (m), 21.6 (m), 22.9 (m), 23.7 (m), 24.2 (s), 25.2 (w), 27.1 (m), 29.6 (vw), 30.2 (w), 34.0 (w);B) polymorph B exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 4.6 (w), 5.3 (vs), 6.2 (s), 7.7 (s), 9.2 (m), 9.6 (m), 10.3 (w), 11.3 (m), 11.7 (w), 12.6 (vw), 13.0 (w), 13.9 (m), 14.7 (vw), 14.9 (w), 15.6 (w), 16.3 (m), 17.0 (vw), 17.4 (vw), 18.0 (w), 18.7 (m), 19.3 (m), 20.0 (s), 20.5 (w), 20.8 (m), 21.2 (w, shoulder), 21.5 (m), 22.4 (m), 23.2 (s), 23.8 (m), 24.4 (vw), 25.2 (w, broad), 26.0 (w), 26.4 (vw), 27.0 (w), 27.9 (vw), 28.9 (w);C) polymorph C exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 4.1 (m), 5.6 (s), 7.8 (m), 8.3 (m), 10.3 (m), 11.6 (w), 17.5 (w), 17.9 (w), 18.7 (m), 19.5 (s), 20.6 (m), 21.5 (vw), 21.9 (m), 23.1 (m), 24.0 (w), 24.8 (w);D) polymorph D exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 5.0 (m), 6.5 (m), 6.8 (s), 8.7 (m), 10.0 (m), 10.2 (m), 10.8 (m), 13.1 (w), 13.5 (m), 14.3 (s), 15.3 (vw), 16.1 (m), 16.8 (w), 18.2 (w), 18.5 (m), 19.0 (w), 19.9 (m), 20.5 (m), 21.0 (vs), 21.7 (s), 22.3 (w), 23.4 (m), 24.0 (m), 25.6 (w), 26.2 (m);E) polymorph E exhibits a characteristic X-ray powder diffraction ...

COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS

The present disclosure is directed to compounds of the structure (X): 3. The compound of claim 1 , wherein L is a polyethylene glycol linker.4. The compound of any one of claim 1 , wherein n is 2.8. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or prodrug thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent or excipient.9. A method of treating irritable bowel disease in a subject in need thereof comprising administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.10. A method of treating chronic kidney disease in a subject in need thereof comprising administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.11. A method of treating end stage renal disease in a subject in need thereof comprising administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof. This application is a continuation application of U.S. patent application Ser. No. 13/172,394, filed Dec. 30, 2009, allowed, which is a continuation of International PCT Patent Application No. PCT/US2009/069852, which was filed on Dec. 30, 2009, now pending, which claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 61/141,853, filed Dec. 31, 2008, U.S. Provisional Patent Application No. 61/169,509, filed Apr. 15, 2009, and U.S. Provisional Patent Application No. 61/237,842, filed Aug. 28, 2009, which applications are incorporated herein by reference in their entireties.1. FieldThe present disclosure is directed to compounds that are substantially active in the gastrointestinal tract to inhibit NHE-mediated antiport of sodium ions and hydrogen ions, and the use of such compounds in the treatment of disorders associated with fluid retention or salt overload and in the treatment of gastrointestinal tract disorders, ...

BCL-2-SELECTIVE APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE DISEASES

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 or Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti-apoptotic Bcl-2 protein. 6. The compound of , , , , or , wherein{'sup': 1', '2, 'Ais C(A); and'}{'sup': '2', 'Ais H.'}7. The compound of , , , , or , wherein{'sup': 1', '2, 'Ais C(A) or N;'}{'sup': '2', 'Ais H; and'}{'sup': 1', '1, 'Bis NHR.'}8. The compound of , , , , or , wherein{'sup': 1', '2, 'Ais C(A) or N;'}{'sup': '2', 'Ais H;'}{'sup': 1', '1, 'Bis NHR; and'}D1 is H.9. The compound of , , , , or , wherein{'sup': 1', '2, 'Ais C(A) or N;'}{'sup': '2', 'Ais H;'}{'sup': 1', '1, 'Bis NHR;'}{'sup': '1', 'Dis H; and'}{'sup': '1', 'Eis H.'}10. The compound of , , , , or , wherein{'sup': 1', '2, 'Ais C(A) or N;'}{'sup': '2', 'Ais H;'}{'sup': 1', '1, 'Bis NHR;'}{'sup': '1', 'Dis H;'}{'sup': '1', 'Eis H; and'}{'sup': '1', 'sub': '2', 'Yis NO.'}11. A compound of claim 1 , wherein the compound is chosen from:4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-phenoxybenzamide;benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-2-phenoxy-N-((4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;2-(benzyloxy)-4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(2-phenylethoxy)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(phenylthio)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-2-(phenylthio)-N-((4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((4-((3-morpholin-4- ...

NOVEL BENZENESULFONAMIDE COMPOUNDS, METHOD FOR SYNTHESIZING SAME, AND USE THEREOF IN MEDICINE AS WELL AS IN COSMETICS

Benzenesulfonamide compounds having a structure of formula (I) are described. Also described, are methods for synthesizing the compounds and to the use thereof in pharmaceutical compositions for human or veterinary medicine and in cosmetic compositions. 2. The method as claimed in claim 1 , wherein the disease is an inflammatory skin disease.3. The method as claimed in claim 2 , wherein the inflammatory skin disease is psoriasis claim 2 , atopic dermatitis claim 2 , or psoriatic arthritis.4. The method as claimed in claim 1 , wherein the disease or disorder is selected from the group consisting of septic shock claim 1 , hemodynamic shock claim 1 , malaria claim 1 , an inflammatory bowel disease (IBD) claim 1 , an inflammatory bone disease claim 1 , a mycobacterial infection claim 1 , meningitis claim 1 , a fibrotic disease claim 1 , a cardiac disease claim 1 , ischemic attack claim 1 , transplant rejection claim 1 , cancer claim 1 , atherosclerosis claim 1 , obesity claim 1 , a disease involving angiogenesis phenomena claim 1 , an autoimmune disease claim 1 , osteoarthritis claim 1 , rheumatoid arthritis claim 1 , ankylosing spondylitis claim 1 , juvenile chronic arthritis claim 1 , multiple sclerosis claim 1 , HIV claim 1 , non-insulin-dependent diabetes mellitus claim 1 , an allergic disease claim 1 , asthma claim 1 , chronic obstructive pulmonary disease (COPD) claim 1 , and ocular inflammation.5. The method as claimed in claim 1 , wherein the disease is a neurological pathological condition selected from the group consisting of Alzheimer's disease claim 1 , Parkinson's disease claim 1 , a Parkinsonian disorder claim 1 , amyotrophic lateral sclerosis claim 1 , an autoimmune disease of the nervous system claim 1 , an autonomic disease of the nervous system claim 1 , dorsal pain claim 1 , cerebral edema claim 1 , a cerebrovascular disorder claim 1 , dementia claim 1 , a nervous system nerve fiber demyelinating autoimmune disease claim 1 , diabetic neuropathy claim ...

Method for Synthesizing Pitavastatin t-Butyl Ester

Method for Synthesizing Pitavastatin t-Butyl Ester A method for synthesizing pitavastatin tert-butyl ester includes obtaining a substance B through reacting (4R-CIS)-6-chloromethyl-2,2-dimethyl-1,3-dioxolane-4-acetic acid tert-butyl ester with a substance A under the action of a first base catalyst, 5 oxidizing with an oxidizing agent to obtain a substance C, then reacting with 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-formaldehyde under the action of a second base catalyst to obtain a substance D, and finally, carrying out an acid deprotection to obtain pitavastatin t-butyl ester. The reaction conditions of the present invention are mild and controllable, and the reaction conditions of the synthesis of the Julia olefination do 10 not require an ultra-low temperature reaction. The operation is convenient and simple, the stereoselectivity is good, the yield is high, and the synthesized pitavastatin t-butyl ester is a completely non-cis isomer, and its purity is high.

SUBSTITUTED DIHYDROINDENE-4-CARBOXAMIDES AND ANALOGS THEREOF, AND METHODS USING SAME

The present invention includes novel substituted bicyclic compounds, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infections in a patient. In certain embodiments, the compounds and compositions of the invention are capsid inhibitors. 2. The compound of claim 1 , wherein each occurrence of Ror Ris independently selected from the group consisting of —(CH)-(optionally substituted heteroaryl) claim 1 , —(CH)-(optionally substituted heterocyclyl) claim 1 , and —(CH)-(optionally substituted aryl).3. The compound of claim 1 , wherein each occurrence of optionally substituted alkyl claim 1 , optionally substituted heterocyclyl claim 1 , or optionally substituted cycloalkyl is independently optionally substituted with at least one substituent selected from the group consisting of C-Calkyl claim 1 , halo claim 1 , —OR claim 1 , optionally substituted phenyl claim 1 , optionally substituted heteroaryl claim 1 , optionally substituted heterocyclyl claim 1 , —N(R)C(═O)R claim 1 , —C(═O)NRR claim 1 , and —N(R)(R) claim 1 , wherein each occurrence of Ris independently H claim 1 , optionally substituted C-Calkyl claim 1 , optionally substituted C-Ccycloalkyl claim 1 , optionally substituted aryl claim 1 , or optionally substituted heteroaryl claim 1 , or two Rgroups combine with the N to which they are bound to form a heterocycle.4. The compound of claim 1 , wherein each occurrence of optionally substituted aryl or optionally substituted heteroaryl is independently optionally substituted with at least one substituent selected from the group consisting of C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-Chaloalkoxy claim 1 , halo claim 1 , —CN claim 1 , —OR claim 1 , —N(R)(R) claim 1 , —NO claim 1 , —S(═O)N(R)(R) claim 1 , acyl claim 1 , and C-Calkoxycarbonyl claim 1 , wherein each occurrence of Ris independently H claim 1 , C-Calkyl claim 1 , or C-Ccycloalkyl.5. The compound of claim 1 , wherein each occurrence of optionally ...

COMPOUNDS AND METHODS FOR INDUCING CHONDROGENESIS

The present invention provides compounds and compositions for the amelioration of arthritis and joint injuries by inducing mesenchymal stem cells into chondrocytes. 2. The method of claim 1 , wherein{'sup': 1', '2', '2, '(a) Lis a bond, Lis —C(O)NH—, ring B is phenyl, Ris —CN or phenyl, and subscript m is 1, or'}{'sup': 1', '2', '1, 'sub': '2', '(b) Ris —C(O)OH, subscript n is 1, ring A is phenyl, Lis —C(O)NH—, and Lis a bond or —CH—, or'}{'sup': 1', '2', '2, 'sub': '2', '(c) each of ring A and ring B is phenyl, Ris —C(O)OH or combined with L, subscript n is 1, and at least one Ris selected from the group consisting of H, —CN and —COH.'}5. The method of claim 4 , wherein each Ris independently selected from the group consisting of —C(O)R claim 4 , —C(O)OR claim 4 , Calkyl-C(O)OR claim 4 , —NRC(O)OR claim 4 , —NRC(O)NRR claim 4 , —SOOR claim 4 , —SONRR claim 4 , —NRSOR claim 4 , and —CN.6. The method of claim 4 , wherein each Ris independently selected from the group consisting of —CH—C(O)OH claim 4 , —C(O)Me claim 4 , —NHC(O)NH claim 4 , —NHC(O)OMe claim 4 , —NHSOMe claim 4 , —SONH claim 4 , —SONHMe claim 4 , —SOH claim 4 , —C(O)OH claim 4 , and —CN.7. The method of claim 4 , whereinring A is phenyl; andsubscript n is 1.8. The method of claim 4 , whereinring A is selected from the group consisting of biphenyl and pyridyl, orsubscript n is 2.11. The method of claim 10 , wherein each Ris independently selected from the group consisting of H claim 10 , —CHNHCONH claim 10 , —CHNHCOOMe claim 10 , —CHNHMe claim 10 , —CHOPh claim 10 , 2-CN claim 10 , 4-CN claim 10 , —C(O)OH claim 10 , —CONHOH claim 10 , —OCF2H claim 10 , —POH claim 10 , —SOH claim 10 , phenyl claim 10 , pyridyl claim 10 , imidazole and tetrazole.13. The method of claim 12 , wherein{'sup': '2', 'sub': 2', '2', '2', '2', '2', '2', '2', '2, 'each Ris independently selected from the group consisting of H, Me, —Cl, —CHOH, —CHCHOH, —CHNH, —C(O)Me, —C(O)OH, —C(O)NH, —CN, morpoholine, 3,4-difluorophenyl and —SONH; ...

HETEROCYCLIC COMPOUNDS FOR TREATING HELMINTH INFECTIONS

Disclosed are compounds of Formula 1, N-oxides, and salts thereof, 3. A compound of whereinQ is Q-24;x is 0, 1, 2 or 3;{'sup': 13a', '13b, 'sub': 't', 'L is (CRR);'}t is 1;{'sup': '13a', 'sub': 1', '2, 'each Ris independently hydrogen, halogen or C-Calkyl;'}{'sup': '2', 'Ris hydrogen or methyl;'}{'sup': 3', '6', '7a', '7b', '8', '9', '10', '11', '12', '10', '11, 'sub': p', '2', '1', '6', '1', '6, 'each Ris independently halogen, cyano, nitro, OR, NRR, C(O)R, C(O)OR, C(O)NRR, S(O)R, S(O)NRR, C-Calkyl or C-Chaloalkyl;'}{'sup': '6', 'sub': 1', '6', '1', '6, 'each Ris independently hydrogen, C-Calkyl or C-Chaloalkyl; and'}m is 0, 1 or 2.4. A compound of wherein{'sup': '1', 'sub': 3', '3', '3', '2, 'each Ris independently fluorine, chlorine, CH, CF, OCFor OCHF;'}{'sup': '2', 'Ris hydrogen; and'}{'sup': 3', '6', '12, 'sub': p', '1', '4', '1', '4, 'each Ris independently halogen, cyano, OR, S(O)R, C-Calkyl or C-Chaloalkyl.'}5. A compound of whereinQ is Q-24;x is 0, 1, 2 or 3;L is O;{'sup': 1', '6, 'sub': 1', '3', '1', '3, 'each Ris independently halogen, cyano, nitro, OR, C-Calkyl or C-Chaloalkyl;'}{'sup': '2', 'Ris hydrogen or methyl;'}{'sup': 3', '6', '7a', '7b', 'S', '9', '10', '11', '12', '10', '11, 'sub': p', '2', '5', '6', '2', '6, 'each Ris independently cyano, nitro, OR, NRR, C(O)R, C(O)OR, C(O)NRR, S(O)R, S(O)NRR, C-Calkyl or C-Chaloalkyl;'}{'sup': 4a', '6, 'sub': 1', '6', '1', '6, 'each Ris independently halogen, cyano, nitro, OR, C-Calkyl or C-Chaloalkyl;'}{'sup': '6', 'sub': 5', '6', '1', '6, 'each Ris independently hydrogen, C-Calkyl and C-Chaloalkyl;'}n is 0, 1 or 2; andm is 0, 1 or 2.6. A compound of that is selected from the group consisting of:4-(3-chloro-2-cyanophenoxy)-N-(4-quinolinylmethyl)benzenesulfonamide;4-(phenylmethyl)-N-(4-quinolinylmethyl)benzenesulfonamide;4-(4-cyanophenoxy)-N-(4-quinolinylmethyl)benzenesulfonamide;4-(2-chloro-4-cyanophenoxy)-N-(4-quinolinylmethyl)benzenesulfonamide;4-(2-cyanophenoxy)-N-(4-quinolinylmethyl)benzenesulfonamide;4 ...

CRYSTALLINE FORMS OF PITAVASTATIN CALCIUM

The present invention is directed to new crystalline forms of Pitavastatin hemicalcium salt, referred to hereinafter as polymorphic Forms A, B, C, D, E and F, as well as the amorphous form. Furthermore, the present invention is directed to processes for the preparation of these crystalline forms and the amorphous form and pharmaceutical compositions comprising these crystalline forms or the amorphous forms. 1A) polymorph A exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 5.0 (s), 6.8 (s), 9.1 (s), 10.0 (w), 10.5 (m), 11.0 (m), 13.3 (vw), 13.7 (s), 14.0 (w), 14.7 (w), 15.9 (vw), 16.9 (w), 17.1 (vw), 18.4 (m), 19.1 (w), 20.8 (vs), 21.1 (m), 21.6 (m), 22.9 (m), 23.7 (m), 24.2 (s), 25.2 (w), 27.1 (m), 29.6 (vw), 30.2 (w), 34.0 (w);B) polymorph B exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 4.6 (w), 5.3 (vs), 6.2 (s), 7.7 (s), 9.2 (m), 9.6 (m), 10.3 (w), 11.3 (m), 11.7 (w), 12.6 (vw), 13.0 (w), 13.9 (m), 14.7 (vw), 14.9 (w), 15.6 (w), 16.3 (m), 17.0 (vw), 17.4 (vw), 18.0 (w), 18.7 (m), 19.3 (m), 20.0 (s), 20.5 (w), 20.8 (m), 21.2 (w, shoulder), 21.5 (m), 22.4 (m), 23.2 (s), 23.8 (m), 24.4 (vw), 25.2 (w, broad), 26.0 (w), 26.4 (vw), 27.0 (w), 27.9 (vw), 28.9 (w);C) polymorph C exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 4.1 (m), 5.6 (s), 7.8 (m), 8.3 (m), 10.3 (m), 11.6 (w), 17.5 (w), 17.9 (w), 18.7 (m), 19.5 (s), 20.6 (m), 21.5 (vw), 21.9 (m), 23.1 (m), 24.0 (w), 24.8 (w);D) polymorph D exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 22 at 5.0 (m), 6.5 (m), 6.8 (s), 8.7 (m), 10.0 (m), 10.2 (m), 10.8 (m), 13.1 (w), 13.5 (m), 14.3 (s), 15.3 (vw), 16.1 (m), 16.8 (w), 18.2 (w), 18.5 (m), 19.0 (w), 19.9 (m), 20.5 (m), 21.0 (vs), 21.7 (s), 22.3 (w), 23.4 (m), 24.0 (m), 25.6 (w), 26.2 (m);E) polymorph E exhibits a characteristic X-ray powder diffraction ...

COMPOSITION AND METHOD FOR PREVENTION, MITIGATION OR TREATMENT OF AN ENTEROPATHOGENIC BACTERIAL INFECTION

Bicyclic compounds for decreasing the expression of bacterial virulence factors thereby preventing, mitigating, or treating bacterial infection are provided. 2. The compound or hydrate claim 1 , isomer claim 1 , prodrug or pharmaceutically acceptable salt of claim 1 , wherein X is —NH— claim 1 , —C═N— claim 1 , —N═C— claim 1 , —C—NH— or —NH—C—.3. The compound or hydrate claim 1 , isomer claim 1 , prodrug or pharmaceutically acceptable salt of claim 1 , wherein X is —CHCH—.5. The compound claim 1 , or hydrate claim 1 , isomer claim 1 , prodrug or pharmaceutically acceptable salt of claim 1 , wherein n is 0.6. The compound claim 1 , or hydrate claim 1 , isomer claim 1 , prodrug or pharmaceutically acceptable salt of claim 1 , wherein n is 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 or 6.7. The compound claim 1 , or hydrate claim 1 , isomer claim 1 , prodrug or pharmaceutically acceptable salt of claim 1 , wherein each of a claim 1 , b claim 1 , c or e are double bonds.8. The compound claim 1 , or hydrate claim 1 , isomer claim 1 , prodrug or pharmaceutically acceptable salt of claim 1 , wherein dashed lines a-e are all present or all absent or dashed lines a claim 1 , b and c are present and e and d are absent.11. A pharmaceutical composition comprising the compound of in admixture with a carrier.12. A method for decreasing expression of a bacterial virulence factor comprising contacting a bacterium that expresses an A/X regulatory protein with a compound of claim 1 , so that the expression of a virulence factor by said bacterium is decreased.13Vibrio cholerae, Escherichia coli, Shigella flexneri, Yersinia enterocolitica, Yersinia pestis, Brucella abortus Salmonella typhi, Bacillus anthracis, Clostridium botulinum, Listeria monocytogenes, Staphylococcus aureusSalmonella typhimurium.. The method of claim 12 , wherein the bacterium is or14. A method for preventing claim 1 , mitigating claim 1 , or treating an infection by a bacterium that expresses an A/X ...

Nrf2 activator

Provided are compounds of Formula A or I, or pharmaceutically acceptable salts thereof, and methods for their use and production.

PRODRUGS OF NH-ACIDIC COMPOUNDS

The invention provides a method of sustained delivery of a lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug by administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile conjugates of parent drugs that are derivatized through carbonyl linked prodrug moieties. The prodrug compounds of the invention can be used to treat any condition for which the lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug is useful as a treatment. 19-. (canceled)14. The compound of claim 10 , wherein B is selected from the group consisting of a bond claim 10 , a straight chain C-Calkyl claim 10 , C-Calkenyl claim 10 , alkynyl claim 10 , alkoxy claim 10 , alkoxyC-Calkoxy claim 10 , alkylamino claim 10 , alkoxyC-Calkylamino claim 10 , alkylcarbonylamino claim 10 , alkylaminocarbonyl claim 10 , aryloxyC-Calkoxy claim 10 , aryloxyC-Calkylamino claim 10 , aryloxyC-Calkylamino carbonyl claim 10 , C-C-alkylaminoalkylaminocarbonyl claim 10 , alkyl(N-alkyl)aminoalkyl-aminocarbonyl claim 10 , alkylaminoalkylamino claim 10 , alkylcarbonylaminoalkylamino claim 10 , alkyl(N-alkyl)aminoalkylamino claim 10 , (N-alkyl)alkylcarbonylaminoalkylamino claim 10 , alkylaminoalkyl claim 10 , alkylaminoalkylaminoalkyl claim 10 , alkylpiperazinoalkyl claim 10 , piperazinoalkyl claim 10 , alkylpiperazino claim 10 , alkenylaryloxyC-Calkoxy claim 10 , alkenylarylaminoC-Calkoxy claim 10 , alkenylaryllalkylaminoC-Calkoxy claim 10 , alkenylaryloxyC-Calkylamino claim 10 , alkenylaryloxyC-Calkylaminocarbonyl claim 10 , piperazinoalkylaryl claim 10 , heteroarylC-Calkyl claim 10 , heteroarylC-Calkenyl claim 10 , heteroarylC-Calkynyl claim 10 , heteroarylC-Calkylamino claim 10 , heteroarylC-Calkoxy claim 10 , heteroaryloxyC-Calkyl claim 10 , heteroaryloxyC-Calkenyl ...

CYTOTOXIC COMPOUNDS WHICH ARE INHIBITORS OF THE POLYMERISATION OF TUBULIN

The invention relates to compounds which are inhibitors of the polymerization of tubulin, to the methods for the production thereof, and to the uses of same. 116.-. (canceled)18. The compound according to claim 17 , wherein the dashed bond is present.21. The compound according to claim 20 , wherein the dashed bond is present.24. The compound according to wherein Zand Zare a hydrogen atom.25. The compound according to wherein Zand Zare a fluorine atom.26. The compound according to wherein n is 1 claim 17 , X and Z are a nitrogen atom claim 17 , A and E are claim 17 , independently of each other claim 17 , a nitrogen or carbon atom claim 17 , and Y and B are a carbon atom.28. A method for treating or preventing a proliferative disease claim 17 , comprising administering to a person in need thereof an effective amount of a compound according to .29. The method according to claim 28 , wherein the proliferative disease is cancer claim 28 , psoriasis or fibrosis.30. A method for treating or preventing a vascular disease claim 17 , comprising administering to a person in need thereof an effective amount of a compound according to .31. A conjugate comprising a compound according to bound covalently to an antibody.32. A pharmaceutical composition comprising a compound according to .33. A pharmaceutical composition comprising a conjugate according to .34. The pharmaceutical composition according to further comprising at least one other active ingredient.35. The pharmaceutical composition according to wherein the other active ingredient is selected from 6-mercaptopurine claim 34 , fludarabine claim 34 , cladribine claim 34 , pentostatin claim 34 , cytarabine claim 34 , 5-fluorouracil claim 34 , gemcitabine claim 34 , methotrexate claim 34 , raltitrexed claim 34 , irinotecan claim 34 , topotecan claim 34 , etoposide claim 34 , daunorubicin claim 34 , doxorubicin claim 34 , epirubicin claim 34 , idarubicin claim 34 , pirarubicin claim 34 , mitoxantrone claim 34 , chlormethine ...

TLR7/8 ANTAGONISTS AND USES THEREOF

The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TLR7/8 antagonists. 2. The compound of claim 1 , wherein Ring A is Caryl or a 6 membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.3. The compound of claim 2 , wherein Ring A is phenyl claim 2 , pyridyl claim 2 , pyrimidinyl claim 2 , pyrazinyl claim 2 , pyridazinyl claim 2 , or triazinyl.5. The compound of claim 1 , wherein Ring B is a 5-6 membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.7. The compound of claim 1 , wherein X is C(R).8. The compound of claim 1 , wherein Y is C(R)or NR.9. The compound of claim 1 , wherein each Ris independently Caliphatic claim 1 , —C(O)R claim 1 , —C(NH)NR claim 1 , —NRC(O)R claim 1 , —N(R); or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur; each of which is optionally substituted.11. The compound of claim 1 , wherein each Ris independently Caliphatic claim 1 , Caryl claim 1 , a 3-8 membered saturated or partially unsaturated carbocyclic ring claim 1 , a 3-7 membered heterocylic ring having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur claim 1 , or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur; each of which is optionally substituted.12. The compound of claim 11 , wherein each Ris independently methyl claim 11 , ethyl claim 11 , ethyl claim 11 , propyl claim 11 , i-propyl claim 11 , butyl claim 11 , s-butyl claim 11 , t-butyl claim 11 , straight or branched pentyl claim 11 , or straight or branched hexyl; each of which is optionally substituted.15. The compound of claim 1 , selected from Table 1.16. A pharmaceutical composition comprising ...

METHOD OF PREPARING MALONONITRILE OXIME ETHER COMPOUND AND INTERMEDIATE COMPOUND

Provided are a method of preparing a malononitrile oxime ether compound and an intermediate compound. The malononitrile oxime ether compound has a structure as shown in formula (VII), wherein W is selected from aryl or heteroaryl. The preparation method comprises steps: reacting a first raw material with a second raw material in the presence of a first solvent and a catalyst to obtain the intermediate compound, wherein the first raw material has a structure as shown in formula (IV), and the second raw material has a structure as shown in formula (V); and subjecting the intermediate compound as shown in formula (VI), and, a dehyclrant to a dehydrantion reaction in the presence of a second solvent to obtain the malononitrile oxime ether compound. In the preparation process for the intermediate, a cheaper cyanoacetamide is used as a raw material, the reaction conditions are mild. Moreover, the yield of the intermediate compound is high and the cost of the process is low. Furthermore, the required malononitrile oxime ether compound, is obtained only through one-step dehydration reaction. Using the preparation method, is advantageous for improving the yield of malononitrile oxime ethers and reducing the cost of the process. 2. The preparation method according to claim 1 , wherein in the dehydration reaction process claim 1 , a molar ratio of the intermediate compound and the dehydrating agent is 1 to (1-20).3. The preparation method according to claim 1 , wherein the dehydrating agent is one or more selected from a group consisting of acetic anhydride claim 1 , bistrichlomm ethyl carbonate claim 1 , thionyl chloride claim 1 , phosphorus oxychlonde and phosphorus pentoxide claim 1 , and preferably claim 1 , is thionyl claim 1 , chloride and/or phosphorus oxychloride; andthe solvent is one or more selected from a. group consisting of halogenated alkane compounds, aromatic hydrocarbon compounds, nitrite compounds and DMF, and preferably, is trichloromethane, dichloroethane, ...

PENTAFLUOROSULFANYL-SUBSTITUTED AMIDE DERIVATIVES, PREPARATION METHODS THEREOF AND MEDICAL USES THEREOF

The present invention relates to a novel pentafluorosulfanyl-substituted amide compound that regulates or inhibits indoleamine 2,3-dioxygenase (IDO) activity, its preparation method and its application in medicine. Specifically, the present invention relates to a compound represented by general formula (I) and pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the compound or pharmaceutically acceptable salt thereof, application of the compound or pharmaceutically acceptable salt thereof for treating and/or preventing related disorders mediated by IDO, especially tumors, and a method for preparing the compound or pharmaceutically acceptable salt thereof. The present invention also relates to the preparation of the compound or pharmaceutically acceptable salt thereof or a pharmaceutical composition containing the compound or pharmaceutically acceptable salt thereof for the treatment and/or prevention of IDO-mediated related disorders, especially for use in tumor treatment. The substituents in the general formula (I) are the same as descripted in the specification. 2. The compound according to claim 1 , or pharmaceutically acceptable salt claim 1 , prodrug claim 1 , stable isotope derivative claim 1 , isomer or mixture thereof claim 1 , whereRing A is a phenyl ring or a pyridyl ring;B is —C(O)— or —NH—;When B is —C(O)—, C is —NH—; when B is —NH—, C is —C(O)—;{'sup': '3', 'D is N or CR;'}{'sup': '4', 'E is N or CR;'}G is an optionally substituted 5-10 membered heteroaryl or 6-10 membered aryl;L is a bond or —O—;{'sup': 1', '2', '2, 'sub': 1-4', '3-6', '1, 'Rand Rare each independently selected from H or an optionally substituted Calkyl, Ccycloalkyl or 4-7 membered heterocyclic group; alternatively, Rand Rtogether with the carbon atom to which they are attached form a 3-7 membered ring containing heteroatom(s) optionally selected from O, N and S;'}{'sup': 3', '4, 'sub': 1-4', '1-4, 'Rand Rare each independently selected from H, halogen, CN ...

SPIRO COMPOUND AS INDOLEAMINE-2,3-DIOXYGENASE INHIBITOR

Disclosed in the present invention are an indoleamine-2,3-dioxygenase inhibitor and a preparation method therefor. The inhibitor of the present invention has a structure as represented by general formula (I), wherein the definitions of Ar, E, Y, X, V, D, W, B, ring A and ring B are as shown in the description and claims. Also disclosed in the present invention is a preparation method for the inhibitor. The compound of general formula (I) of the present invention can be used as an indoleamine-2,3-dioxygenase inhibitor for preparing a medicament for preventing and/or treating indoleamine-2,3-dioxygenase-mediated diseases. 13. The compound of Formula (I) described in is characterized in that the compound is:(±) N-(4-chlorophenyl)-6-(quinoline-4-yl)spiro[3.3]heptane-2-carboxamide;(±) (cis/trans) N-(4-chlorophenyl)-6-(quinoline-4-yl)spiro[2.5]octane-1-carboxamide;(±) N-(4-chlorophenyl)-6-(6-fluoroquinoline-4-yl)spiro[3.3]heptane-2-carboxamide;(±) (cis/trans) N-(4-chlorophenyl)-6-(6-fluoroquinoline-4-yl)spiro[2.5]octane-1-carboxamide;(±) (cis/trans) N-(4-chlorophenyl)-6-(6-fluoroquinoline-4-yl)spiro[2.5]octane-1-carboxamide;(±) (cis/trans) 6-(6-fluoroquinoline-4-yl)-N-(4-(trifluoromethyl)phenyl)spiro[2.5]octane-1-carboxamide(±) (cis/trans) 6-(6-fluoroquinoline-4-yl)-N-phenyl spiro[2.5]octane-1-carboxamide(±) (cis/trans) 4-chlorine-N-(6-(6-fluoroquinoline-4-yl)spiro[2.5]octane-1-yl)benzamide(±) (cis/trans) 1-(4-chlorophenyl)-3-(6-(6-fluoroquinoline-4-yl)spiro[2.5]-octane-1-yl) urea(±) N-(4-chlorophenyl)-7-(6-fluoroquinoline-4-yl)spiro[3.5]nonane-1-carboxamide(±) 1-(4-chlorophenyl)-3-(7-(6-fluoroquinoline-4-yl)spiro[3.5]) nonane-1-yl) urea(±) 4-chlorine-N-(7-(6-fluoroquinoline-4yl)spiro[3.5]nonane-1-yl)benzamide(±) 4-chlorine-N-(7-(6-fluoroquinoline-4yl)spiro[3.5]nonane-1-yl)benzsulfamide(±) N-(3-bromophenyl)-7-(6-fluoroquinoline-4-yl)spiro[3.5]nonane-1-carboxamideN-(4-chlorophenyl)-7-(6-fluoroquinoline-4-yl)spiro[3.5]nonane-2-carboxamide (enantiomer 1)N-(4-chlorophenyl)-7 ...

FLUORESCENT PROBE FOR DETECTING NITROREDUCTASE AND PREPARATION METHOD AND USE THEREOF IN ENZYMATIC REACTION

The present invention relates to a fluorescent probe for detecting nitroreductase and a preparation method and use thereof in enzymatic reactions, belonging to the field of industrial analysis and detection. The fluorescent probe is 3-(4-(2-(4′-(diphenylamino)-3-((4-nitrobenzyl)oxy)-[1,1′-biphenyl]-4-yl)vinyl)quinolin-1-ium-1-yl)propane-1-sulfonate. The fluorescent probe of the present invention, with the introduction of hydrophilic groups, sulfonate and quinolinium, the probe's hydrophilicity is enhanced, under the enzymatic catalysis of nitroreductase (NTR), 1,6-rearrangement and elimination reaction occurs, and hydroxyl group is generated. Detection and analysis of the NTR in the industrial enzymatic reactions can be realized due to the change of fluorescence which is induced by the intramolecular charge transfer (ICT) effect. This method has such advantages as easy preparation, high yield and being suitable for detecting high concentration of enzyme in the enzymatic reactions, and it shows an extensive application prospect in the field of enzyme-detection in the industrial enzymatic reaction systems. 2. A preparation method of the fluorescent probe for detecting nitroreductase according to claim 1 , wherein comprising the following steps:(1) dissolving 4′-(diphenylamino)-3-hydroxy-[1,1′-biphenyl]-4-carbaldehyde into dimethyl sulfoxide and dissolving 1-(bromomethyl)-4-nitrobenzene into tetrahydrofuran, followed by ultrasonic treatment respectively and then mixing together, adding cesium carbonate, controlling a reaction temperature in the range of 50° C.-150° C., separating and purifying a reaction product to obtain 4′-(diphenylamino)-3-((4-nitrobenzyl)oxy)-[1,1′-biphenyl]-4-carbaldehyde in yellow solid powder;(2) dissolving 3-(4-methylquinoline-1-bromine)propane-1-sulfonate into pyridine, then adding acetic acid, followed by sufficient mixing, then adding the 4′-(diphenylamino)-3-((4-nitrobenzyl)oxy)-[1,1′-biphenyl]-4-carbaldehyde obtained in step (1), heating ...

NOVEL TRIAZOLE DERIVATIVES

The present invention relates to novel triazole derivatives, to processes for preparing these compounds, to compositions comprising these compounds, and to the use thereof as biologically active compounds, especially for control of harmful microorganisms in crop protection and in the protection of materials and as plant growth regulators. 2. Triazole derivative of formula (I) and/or salt and/or N-oxide according to claim 1 , wherein{'sup': '1', 'sub': 1', '8', '4', '8', '2', '8', '2', '8, 'Rrepresents substituted or non-substituted C-C-alkyl; substituted or non-substituted C-C-cycloalkylalkyl; substituted or non-substituted C-C-alkenyl; substituted or non-substituted C-C-alkynyl;'}{'sup': 2', '3a', '3b', '3c, 'sub': 1', '8', '2', '2', '2', '1', '8', '3', '7', '1', '8', '1', '8', '1', '8, 'Rrepresents H, C-C-alkyl, —Si(R)(R)(R)), —P(O)(OH), —CH—O—P(O)(OH), substituted or non-substituted —C(O)—C-C-alkyl; substituted or non-substituted —C(O)—C-C-cycloalkyl, substituted or non-substituted —C(O)NH—C-C-alkyl; substituted or non-substituted —C(O)N-di-C-C-alkyl; substituted or non-substituted —C(O)O—C-C-alkyl;'}{'sup': 3a', '3b', '3c, 'sub': 1', '8, 'R, R, Rindependent from each other represent a substituted or non-substituted C-C-alkyl;'}andX represents a substituted or non-substituted unsaturated 6 membered heterocycle containing 1 or 2 nitrogen atom(s) as heteroatom(s) or a benzannulated derivative thereof, with the provisio that X does not represent 2-pyridinyl.3. Triazole derivative of formula (I) and/or salt and/or N-oxide according to claim 1 , wherein{'sup': '1', 'sub': 1', '8, 'Rrepresents substituted or non-substituted C-C-alkyl;'}{'sup': '2', 'sub': 1', '8', '1', '8, 'Rrepresents H, C-C-alkyl, substituted or non-substituted —C(O)—C-C-alkyl;'}andX represents a substituted or non-substituted 3-pyridinyl, 4-pyridinyl, 4-pyrimidinyl, 5-pyrimidinyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, quinoline-2-yl or quinoline-3-yl.4. Method for controlling one or more ...

BIARYL KINASE INHIBITORS

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1. 1. A compound which is:or a pharmaceutically acceptable salt thereof. This Continuation application claims the benefit of U.S. Ser. No. 15/865,848 filed Jan. 9, 2018, now allowed, which claims the benefit of U.S. Ser. No. 15/300,618 filed Sep. 29, 2016, now U.S. Pat. No. 9,902,722, which is a 371 of PCT/US2015/023805 filed Apr. 1, 2015, now pending, which claims the benefit of Provisional application U.S. Ser. No. 61/973,942 filed Apr. 2, 2014, now expired and Provisional application U.S. Ser. No. 61/061,591 filed Oct. 8, 2014, now expired, hereby incorporated by reference in their entireties.The present disclosure is generally directed to compounds which can inhibit adaptor associated kinase 1 (AAK1), compositions comprising such compounds, and methods for inhibiting AAK1.Adaptor associated kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases. AAK1 mRNA exists in two splice forms termed short and long. The long form predominates and is highly expressed in brain and heart (Henderson and Conner, 2007, 18, 2698-2706). AAK1 is enriched in synaptosomal preparations and is co-localized with endocytic structures in cultured cells. AAK1 modulates clatherin coated endocytosis, a process that is important in synaptic vesicle recycling and receptor-mediated endocytosis. AAK1 associates with the AP2 complex, a hetero-tetramer which links receptor cargo to the clatherin coat. The binding of clatherin to AAK1 stimulates AAK1 kinase activity (Conner et. al., 2003, 4, 885-890; Jackson et. al., 2003, 163, 231-236). AAK1 phosphorylates the mu-2 subunit of AP-2, which promotes the binding of mu-2 to tyrosine containing sorting motifs on cargo receptors (Ricotta et. al., 2002, 156, 791-795; Conner and Schmid, 2002, 156, 921-929). Mu2 phosphorylation is not required for ...

METAL-CATALYZED COUPLING OF ARYL AND VINYL HALIDES WITH ALPHA, ALPHA-DIFLUOROCARBONYL COMPOUNDS

The coupling of aryl, heteroaryl, and vinyl halides with α,α-difluoroketones or silyl ethers or siylenol ethers of α,α-difluoroketones and α,α-difluoroamides and esters are described. Further derivatization of the coupling products (such as ketone cleavage and Baeyer-Villiger oxidation) is also described. 2. The composition according to claim 1 , wherein said complex is present in said composition in an amount of less than 10 mol % relative to said α claim 1 ,α-difluoromethyl carbonyl compound.3. The composition according to claim 2 , wherein said complex is present in said composition in an amount of about 2 mol % to about 5 mol % relative to said α claim 2 ,α-difluoromethyl carbonyl compound.5. The composition according to claim 4 , wherein said complex is present in said composition in an amount of less than 10 mol % relative to said silyl enol ether.6. The composition according to claim 5 , wherein said complex is present in said composition in an amount of about 2 mol % to about 5 mol % relative to said silyl enol ether.76. The composition according to any one of - claims 4 , wherein said composition does not contain BuSnF.87. The composition according to any one of - claims 4 , wherein said composition does not contain an organotin reagent.98. The composition according to any one of - claims 4 , wherein R claims 4 , R claims 4 , and Rare independently selected from unsubstituted C claims 4 , C claims 4 , C claims 4 , C claims 4 , Cand Calkyl.10. The composition according to claim 9 , wherein one or more of R claim 9 , R claim 9 , and Rare methyl.11. The composition according to any preceding claim claim 9 , further comprising a solvent.12. The composition according to claim 11 , wherein said solvent is a non-polar claim 11 , organic solvent.13. The composition according to claim 12 , wherein said solvent is toluene.14. The composition according to any preceding claim claim 12 , wherein said base is a member selected from CsCOand KPO.17. The composition ...

Amine salts of pitavastatin and rosuvastatin

The present invention relates to unsaturated amine salts of HMG-CoA reductase inhibitors, to a method of producing said amine salts and to the use of said amine salts in the production of pharmaceutically acceptable salts of HMG-CoA reductase inhibitors.

PHARMACEUTICALLY ACCEPTABLE AMINE SALTS OF PITAVASTATIN

The present invention relates to pharmaceutically acceptable amine salts of pitavastatin and a method for producing pharmaceutically acceptable amine salts of pitavastatin. Also provided are pharmaceutical compositions of these amine salts or solvates thereof, and methods of their use as HMG-CoA reductase inhibitors. 1. A pharmaceutically acceptable amine salt of pitavastatin , wherein said amine is selected from the group consisting of aminopolyols and tetraalkyl ammonium salts.2. The pharmaceutically acceptable amine salt of pitavastatin of wherein said aminopolyol is tromethamine.3. The pharmaceutically acceptable amine salt of pitavastatin of wherein said tetraalkyl ammonium salt is choline.4. A method for the preparation of an amine salt of pitavastatin comprising reacting pitavastatin acid or pitavastatin calcium salt with an amine in a solvent followed by precipitating said amine salt of pitavastatin claim 1 , wherein said reacting is carried out at a first temperature and said precipitating is carried out at a second temperature that is at least 5° C. below said first temperature.6. Method according to wherein said amine is selected from the group consisting of amino acids claim 4 , aminopolyols claim 4 , amino sugars claim 4 , ammonia claim 4 , ethyl amine derivatives claim 4 , guanines claim 4 , purines claim 4 , tetraalkyl ammonium salts and vitamins.7. Method according to wherein said amine is an amino acid selected from the group consisting of histidine claim 6 , lysine and ornithine.8. Method according to wherein said amine is tromethamine.9. Method according to wherein said amine is an amino sugar selected from the group consisting of daunosamine claim 6 , galactosamine claim 6 , glucosamine and N-methylglucamine.10. Method according to wherein said amine is an ethyl amine derivative selected from the group consisting of benzathine claim 6 , diethyl amine claim 6 , ethanol amine claim 6 , ethyl amine claim 6 , ethylene diamine claim 6 , 1-(2- ...

CRYSTAL FORM OF QUINOLINE COMPOUND AND PROCESS FOR ITS PRODUCTION

A method for producing a drug substance of crystalline pitavastatin calcium excellent in stability, is presented. In the production of a compound (pitavastatin calcium) represented by the formula (1): 2. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 5% (w/w) or greater.3. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 5 to 15% (w/w).4. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 7% (w/w) or greater.5. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 7 to 13% (w/w).6. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 7 to 15% (w/w).7. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 9% (w/w) or greater.8. The method according to claim 1 , comprising maintaining the water content of the pitavastatin calcium salt at 9 to 13% (w/w).17. The method according to claim 9 , wherein drying the crystals comprises drying under reduced pressure.18. The method according claim 9 , wherein drying the crystals comprises drying at a temperature of from 15 to 40° C.19. The method according to claim 1 , wherein maintaining the water content of the pitavastatin calcium salt comprises storing under air tight conditions.20. The method according to claim 1 , wherein the X-ray powder diffraction pattern of the pitavastatin calcium salt claim 1 , as measured using CuKα radiation claim 1 , exhibits peaks at diffraction angles (2θ) of 4.96° claim 1 , 6.72° claim 1 , 9.08° claim 1 , 10.40° claim 1 , 10.88° claim 1 , 13.20° claim 1 , 13.60° claim 1 , 13.96° claim 1 , 18.32° claim 1 , 20.68° claim 1 , 21.52° claim 1 , 23.64° claim 1 , 24.12° claim 1 , 27.00° claim 1 , and 30.16°.21. A pharmaceutical or veterinary medicine ...

Heterocyclic Lipoxin Analogs and Uses Thereof

The present invention relates to a compound of formula (I): wherein L is an optionally substituted heterocyclic group excluding unsubstituted monocyclic pyridine groups; wherein a is 0, 1 or 2; wherein Ris H or with Ris a bond; wherein Ris an optionally substituted alkoxy or aryloxy group, or with Rforms a bond; wherein Ris an optionally substituted alkyl group; and wherein Ris CH, CMeor O. Such compounds may be used in the treatment or prophylaxis of a disease or condition in which inhibition of acute inflammation and/or promotion of its resolution and/or suppression of fibrosis. 2. The compound according to claim 1 , wherein L is selected from an optionally substituted pyrimidine claim 1 , quinoline claim 1 , isoquinoline claim 1 , quinazoline claim 1 , five-membered heterocyclic ring or benzo-fused five membered heterocyclic ring.6. The compound according to claim 1 , wherein Ris a Calkoxy group.8. The compound according to claim 1 , wherein Ris an optionally substituted Calkyl group.11. A composition comprising a compound according to and a pharmaceutically acceptable diluent claim 1 , lubricant or carrier.12. A medicament comprising the composition according to .13. The medicament according to for use in the treatment or prophylaxis of a disease or condition in which inhibition of acute inflammation and/or promotion of its resolution and/or suppression of fibrosis is beneficial.14. The medicament according to for use in the treatment or prophylaxis of atherosclerosis.15. The medicament according to for use in the treatment or prophylaxis of macrovascular complications claim 12 , microvascular complications claim 12 , or both claim 12 , associated with a metabolic disease.16. A medicament comprising the compound of .17. The medicament of for use in the treatment or prophylaxis of a disease or condition in which inhibition of acute inflammation and/or promotion of its resolution and/or suppression of fibrosis is beneficial.18. The medicament of for use in the ...

HDAC8 INHIBITORS FOR TREATING CANCER

Provided herein, inter alia, are compound and methods of treating cancer by inhibiting HDAC8. 138.-. (canceled)40. The compound of claim 39 , wherein X is —C(R)—.41. The compound of claim 39 , wherein Ris halogen claim 39 , —CF claim 39 , —OR claim 39 , —NO claim 39 , substituted or unsubstituted alkyl claim 39 , or substituted or unsubstituted heteroalkyl.42. The compound of claim 39 , wherein Ris hydrogen claim 39 , halogen claim 39 , or —OR.43. The compound of claim 39 , wherein Y is a bond or —N(R)—.44. The compound of claim 39 , wherein Lis a bond claim 39 , —C(O)— claim 39 , —O— claim 39 , —NH— claim 39 , substituted or unsubstituted alkylene claim 39 , substituted or unsubstituted heteroalkylene claim 39 , substituted or unsubstituted cycloalkylene claim 39 , substituted or unsubstituted heterocycloalkylene claim 39 , substituted or unsubstituted arylene claim 39 , or substituted or unsubstituted heteroarylene.45. The compound of claim 39 , wherein Ris halogen claim 39 , —CF claim 39 , —NO claim 39 , —NH claim 39 , —OR claim 39 , substituted or unsubstituted alkyl claim 39 , substituted or unsubstituted heteroalkyl claim 39 , substituted or unsubstituted cycloalkyl claim 39 , substituted or unsubstituted heterocycloalkyl claim 39 , substituted or unsubstituted aryl claim 39 , or substituted or unsubstituted heteroaryl.46. The compound of claim 39 , wherein Ris{'sup': 11', '10', '10', '10', '10', '10, 'R-substituted or unsubstituted alkyl, R-substituted or unsubstituted heteroalkyl, R-substituted or unsubstituted cycloalkyl, R-substituted or unsubstituted heterocycloalkyl, R-substituted or unsubstituted aryl, or R-substituted or unsubstituted heteroaryl; and wherein'}{'sup': '10', 'sub': 3', '3', '3', '3', '3', '3', '2', '3', '2', '2', '2', '2', '2', '2', '2, 'Ris hydrogen, halogen, —N, —CF, —CCl, —CBr, —CI, —CN, —C(O)H, —OCH, —OCHCH, —NH, —COOH, —CONH, —NO, —SH, —S(O)H, —NHNH, —ONH, —NHC(O)NHNH, substituted or unsubstituted heteroalkyl, substituted or ...

ANTI-ANGIOGENIC COMPOUNDS

(E)-2-(2-Quinolin-2-yl-propenyl)-phenol, 2-Quinolin-2-yl-ylethynyl-phenol and salts thereof are useful as medicaments, especially for treatment of an angiogenesis-related disease or disorder. 2. The compound as claimed in wherein the salt is a HCl salt.4. The composition as claimed in wherein the salt is a HCl salt of the compound.5. The composition as claimed in further comprising a pharmaceutically acceptable excipient.6. The composition as claimed in in a form for topical administration.7. The composition as claimed in in the form of eye drops.8. The composition as claimed in in a form for systemic administration.9. The composition as claimed in in the form of an injectable solution or suspension.11. The method as claimed in wherein the angiogenesis-related disease or disorder is associated with neovascularisation of the eye.12. The method as claimed in wherein the angiogenesis-related disease or disorder is associated with blindness.13. The method as claimed in wherein the angiogenesis-related disease or disorder is age-related macular degeneration or diabetic retinopathy.14. The method as claimed in wherein the age-related macular degeneration is wet age-related macular degeneration.15. The method as claimed in wherein the angiogenesis-related disease or disorder is cancer.16. The method as claimed in wherein the cancer is a solid tumour forming cancer.17. The method as claimed in wherein the cancer is colorectal cancer.18. The method as claimed in wherein the cancer is oesophageal cancer.19. The method as claimed in wherein the cancer is breast cancer. The invention relates to anti-angiogenic compounds.In many human diseases there is an inappropriate growth of new blood vessels (angiogenesis). Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels (Ferrara and Kerbel, 2005). Angiogenesis may be a therapeutic target for combating diseases characterised by poor vascularisation or abnormal vasculature (Ferrara ...

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 , ...

NOVEL BENZYLAMINE DERIVATIVES AND THEIR UTILITY AS CHOLESTEROL ESTER-TRANSFER PROTEIN INHIBITORS

The present invention provides, among other things, new benzylamine compounds, compositions comprising benzylamine compounds, methods of making benzylamine compounds, and methods of using benzylamine compounds for treating or preventing a variety of conditions or diseases associated with lipoprotein metabolism. 220.-. (canceled)25. The compound according to claim 24 , wherein claim 24 ,{'sup': 1', '2, 'Rand Rare selected independently from an alkyl, a cycloalkyl or a (cycloalkyl)alkyl, any of which having up to 10 carbon atoms;'}{'sup': 'a', 'Ris selected independently from: 1) a hydrogen; or 2) an alkyl, a cycloalkyl, a cycloalkyl(alkyl), or an aryl, any of which having up to 10 carbon atoms; and'}{'sup': 'a2', 'Ris hydrogen or an alkyl having up to 10 carbon atoms.'}28. The compound according to claim 27 , wherein:{'sup': 1', '2, 'Rand Rare selected independently from an alkyl, a cycloalkyl or a (cycloalkyl)alkyl, any of which having up to 10 carbon atoms;'}{'sup': 'a', 'R, in each occurrence, is selected independently from: 1) hydrogen; or 2) an alkyl, a cycloalkyl, a cycloalkyl(alkyl), or an aryl, any of which having up to 10 carbon atoms; and'}{'sup': 'a2', 'Ris selected from hydrogen or an alkyl having up to 10 carbon atoms.'}2957.-. (canceled)58. The compound according to claim 1 , wherein the compound is:(5-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazole-5-yl)-amino]methyl}-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-cyclobutylmethyl-ethyl-amine;(5-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazole-5-yl)-amino]methyl}-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-bis-cyclopropylmethylethyl-amine;(5-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazole-5-yl)-amino]methyl}-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-cyclopropylmethyl-ethyl-amine;(5-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazole-5-yl)-amino]methyl}-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-cyclobutylmethyl-methyl-amine;(5-{[(3,5-bis-trifluoromethyl-benzyl)-(2 ...

HETEROARYL DERIVATIVES AND USES THEREOF

The present invention relates to antimalarial compounds and their use against protozoa of the genus , including drug-resistant Plasmodia strains. This invention further relates to compositions containing such compounds and a process for making the compounds. 2. The compound according to wherein A and D are CH claim 1 , and B is CR.3. The compound according to wherein Rand Rare H.4. The compound according to wherein Ris tert-butyl and Ris H.5. The compound according to wherein:{'sup': 2', '5', '5, 'sub': '6-10', 'Ris tert-butyl, Caryl optionally substituted with 1, 2, or 3 R, or heteroaryl attached through a carbon atom of the heteroaryl ring optionally substituted with 1, 2, or 3 groups of R.'}6. The compound according to wherein Ris tert-butyl.7. The compound according to wherein Ris pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , or thienyl attached through a carbon atom of the heteroaryl ring claim 1 , optionally substituted with 1 claim 1 , 2 claim 1 , or 3 R.8. The compound according to wherein Ris thiophenyl claim 1 , quinolinyl claim 1 , isoquinolinyl claim 1 , benzofuranyl claim 1 , benzothiophenyl claim 1 , or pyrazolyl each optionally substituted with 1 claim 1 , 2 claim 1 , or 3 R.9. The compound according to wherein:{'sup': '2', 'A and D are CH, and B is CR;'}{'sup': 3', '3a, 'Rand Rare H;'}{'sup': 4', '4a, 'Ris tert-butyl and Ris H;'}{'sup': 2', '5', '5, 'sub': '6-10', 'Ris tert-butyl, Caryl optionally substituted with 1, 2, or 3 groups of R, or heteroaryl attached through a carbon atom of the heteroaryl ring optionally substituted with 1, 2, or 3 R,'}{'sup': 1', '5, 'Ris pyridyl, pyrimidinyl, pyrazinyl, or thienyl, attached through a carbon atom of the heteroaryl ring, optionally substituted with 1, 2, or 3 R.'}10. The compound according to wherein:{'sup': '2', 'A and D are CH, and B is CR;'}{'sup': 3', '3a, 'Rand Rare H;'}{'sup': 4', '4a, 'Ris tert-butyl and Ris H;'}{'sup': '2', 'Ris tert-butyl;'}{'sup': 1', '5, 'Ris pyridyl, pyrimidinyl, ...

Cadherin-11 Inhibitors and Methods of Use Thereof

Cadherin-11 inhibitors and methods for the prevention and treatment of cadherin-11 related diseases are described herein. Cadherin-11 related diseases include cancer and rheumatoid arthritis. 2. (canceled)3. (canceled)4. (canceled)5. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. A composition comprising a compound of and a pharmaceutically acceptable carrier.13. (canceled)15. (canceled)19. (canceled)20. (canceled)21. (canceled)22. (canceled)24. (canceled)26. (canceled)27. (canceled)28. (canceled)31. The method of claim 14 , wherein the cadherin-11 related disease is rheumatoid arthritis.32. The method of claim 14 , wherein the cadherin-11 related disease is a cancer.33. The method of claim 32 , wherein the cancer is breast cancer claim 32 , prostate cancer claim 32 , glioma claim 32 , glioblastoma claim 32 , myeloma claim 32 , leukemia claim 32 , a poor prognosis or invasive cancer claim 32 , a basal-like cancer claim 32 , a mesenchymal-like cancer claim 32 , or metastatic.34. (canceled)35. (canceled)36. (canceled)37. (canceled)38. (canceled)39. (canceled)40. (canceled)41. (canceled)42. (canceled)43. The method of claim 14 , wherein the method further comprises administering a second therapeutic agent to the subject.44. The method of claim 43 , wherein the second therapeutic agent is a chemotherapeutic agent or an anti-inflammatory agent.45. (canceled)46. A method of preventing or treating cancer in a subject claim 43 , comprising:a) selecting a subject with a poor prognosis cancer; andb) administering to the subject a cadherin-11 inhibitor.47. (canceled)48. The method of claim 46 , wherein the cadherin-11 inhibitor is an antibody. This application is a continuation of U.S. application Ser. No. 13/148,579, filed Feb. 8, 2012, which is currently pending and which is a U.S. national stage filing of PCT/US10/23556, filed Feb. 9, 2010, which claims priority to U.S. Provisional Application No. 61/151,038, filed Feb. 9, 2009. These ...

THERMOPLASTIC RESIN, OPTICAL FILM MADE THEREFROM, DIOL COMPOUND, DIESTER COMPOUND

A thermoplastic resin may have a structural unit of formula (1): 2. The thermoplastic resin of claim 1 , comprising the structural unit of formula (1) in an amount in a range of from 1 to 70 wt %.3. The thermoplastic resin of claim 1 , having an absolute value of a photoelastic coefficient of 20×10Paor less.4. The thermoplastic resin of claim 1 , having a glass transition temperature in a range of from 110 to 160° C.5. The thermoplastic resin of claim 1 , comprising at least one selected from the group consisting of a polycarbonate claim 1 , a polyester claim 1 , and a polyester carbonate.8. A transparent film claim 1 , comprising the resin of .9. A retardation film claim 8 , comprising the transparent film of claim 8 , stretched in at least one direction.10. The retardation film of claim 9 , wherein an R450/R550 ratio of a retardation at a wavelength of 450 nm (R450) and a retardation at a wavelength of 550 nm (R550) satisfies formula (I):{'br': None, 'i': R', 'R, '0.50≤450/550≤1.02\u2003\u2003(I).'}11. A circularly polarizing plate claim 9 , comprising the retardation film of . This application is a Continuation of International Application No. PCT/JP2020/024490 filed on Jun. 23, 2020, which claims priority to Japanese Patent Application No. 2019-116226 filed on Jun. 24, 2019. The entire contents of which are incorporated herein by reference.The present disclosure relates to a resin excellent in various properties such as optical property, heat resistance, and moldability; an optical film obtained by using the same; and a diol compound and a diester compound used for producing a resin.Recently, demands for optical transparent resins for use in optical systems such as optical lenses, optical films, and optical recording media have increased. Among them, various optical films have been developed and used for the purpose of improving contrast or tinting or enhancing display quality such as increase in viewing angle and prevention of external light reflection because ...

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 ...

NOVEL TRIAZOLE DERIVATIVES

The present invention relates to novel triazole derivatives, to processes for preparing these compounds, to compositions comprising these compounds, and to the use thereof as biologically active compounds, especially for control of harmful microorganisms in crop protection and in the protection of materials and as plant growth regulators. 2. Triazole derivative of formula (I) and/or salt and/or N-oxide according to claim 1 , wherein{'sup': '1', 'sub': 1', '8', '2', '8', '2', '8', '3', '7', '1', '4', '3', '7', '1', '4', '3', '7', '1', '4', '3', '7', '3', '7', '1', '8, 'Rrepresents C-C-haloalkyl; C-C-halooalkenyl; C-C-haloalkynyl; C-C-halocycloalkyl-C-C-alkyl; C-C-halocycloalkyl-C-C-haloalkyl; C-C-cycloalkyl-C-C-haloalkyl; substituted or non-substituted C-C-cycloalkyl; substituted or non-substituted C-C-cycloalkenyl; substituted or non-substituted arylalkyl; substituted or non-substituted arylalkenyl; substituted or non-substituted arylalkynyl; substituted or non-substituted phenoxyalkyl; substituted or non-substituted phenylcycloalkyl; substituted or non-substituted hetaryl; substituted hetarylalkyl; substituted or non-substituted heterocycloalkyl; substituted or non-substituted heterocycloalkyl-C-C-alkyl;'}{'sup': 2', '3a', '3b', '3c, 'sub': 1', '8', '2', '2', '2', '1', '8', '3', '7', '1', '8', '1', '8', '1', '8, 'Rrepresents H, C-C-alkyl, —Si(R)(R)(R), —P(O)(OH), —CH—O—P(O)(OH), substituted or non-substituted —C(O)—C-C-alkyl or substituted, non-substituted —C(O)—C-C-cycloalkyl, substituted or non-substituted —C(O)NH—C-C-alkyl; substituted or non-substituted —C(O)N-di-C-C-alkyl; substituted or non-substituted —C(O)O—C-C-alkyl;'}{'sup': 3a', '3b', '3c, 'sub': 1', '8, 'R, R, Rindependent from each other represent a substituted or non-substituted C-C-alkyl;'}andX represents a substituted or non-substituted unsaturated 6 membered heterocycle containing 1 or 2 nitrogen atom(s) as heteroatom(s) or a benzannulated derivative thereof, with the provisio that X does not ...

4-HYDROXYBENZOMORPHANS

4-Hydroxybenzomorphans containing carboxamide or thiocarboxamide at the 3-position are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. A compound of formula This application is a continuation application of U.S. application Ser. No. 11/760,039, filed Jun. 8, 2007, now allowed, which was a divisional application of U.S. application Ser. No. 11/266,651, filed Nov. 3, 2005, and issued as U.S. Pat. No. 7,262,298 on Aug. 28, 2007. U.S. application Ser. No. 11/266,651 claims priority from U.S. Provisional Application 60/625,348 filed Nov. 5, 2004. The entire disclosures of each of the prior applications are hereby incorporated herein by reference.The invention relates to 4-hydroxybenzomorphans substituted at the 3-position with carboxamide or thiocarboxamide. The compounds are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives, anti-cocaine, and anti-addiction medications.Opiates have been the subject of intense research since the isolation of morphine in 1805, and thousands of compounds having opiate or opiate-like activity have been identified. Many opioid receptor-interactive compounds including those used for producing analgesia (e.g., morphine) and those used for treating drug addiction (e.g., naltrexone and cyclazocine) have been employed in human therapy. Almost all therapeutically useful opioids in the benzazocine and morphinane classes have a phenolic hydroxyl group (OH) at a position which is numbered “8” in the numbering system used for 2,6-methano-3-benzazocines [e.g., cyclazocine and EKC (ethylketocyclazocine)] and which is numbered “3” in the numbering system used for morphinanes (e.g., morphine).Although the compounds of the present invention do not possess the furan ring of the morphinans, the morphinan numbering system will be used:2,6-Methano-3-benzazocines are also known as benzomorphans, and this terminology will be used interchangeably herein.Until the publications of ...

PITAVASTATIN CALCIUM AND PROCESS FOR ITS PREPARATION

The invention provides the process for the preparation of pitavastatin and its pharmaceutically acceptable salts thereof. In particular, the invention provides a process for the preparation of stable pitavastatin calcium in crystalline form having water content less than 5% wt/wt. The present invention also provides stable crystalline form of pitavastatin calcium substantially free from crystal Form-A and use thereof for pharmaceutical compositions. 1. Storage stable pitavastatin calcium having water content less than about 5% wt/wt.2. The stable pitavastatin calcium as claimed in claim 1 , which is crystalline.3. The stable pitavastatin calcium as claimed in claim 1 , wherein the pitavastatin calcium has the X-ray powder diffraction pattern as shown in .4. The stable pitavastatin calcium as claimed in having characteristic X-ray powder diffraction peaks at 2-theta values of about 6.7° claim 1 , 9.0° claim 1 , 11.1° claim 1 , 19.6° claim 1 , 21.0°±0.2°.5. The stable pitavastatin calcium as claimed in claim 1 , which is substantially free from crystal Form-A.6. The stable pitavastatin calcium as claimed in claim 1 , which is substantially free from crystal Form-A and doesn't show an X-ray powder diffraction peak having relative intensity of more than 25% at a diffraction angle (2θ) of 30.16°.7. The stable pitavastatin calcium as claimed in claim 1 , wherein the pitavastatin calcium is substantially free from crystal Form-A and doesn't show an X-ray powder diffraction peak having relative intensity of more than 25% at a diffraction angle (2θ) of 30.16° after storage for 3 months at 40° C. and a relative humidity of 75%.8. The stable pitavastatin calcium as claimed in claim 1 , wherein the pitavastatin calcium is substantially free from crystal Form-A and doesn't show an X-ray powder diffraction peak having relative intensity of more than 25% at a diffraction angle (2θ) of 30.16° after storage for 3 months at 25° C. and a relative humidity of 60%.9. Stable pitavastatin ...

4-hydroxybenzomorphans

4-Hydroxybenzomorphans containing carboxamide or thiocarboxamide at the 3-position are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.

AMINE SALTS OF PITAVASTATIN AND ROSUVASTATIN

The present invention relates to oxygen-comprising amine salts of HMG-CoA reductase inhibitors, to a method of producing said amine salts and to the use of said amine salts in the production of pharmaceutically acceptable salts of HMG-CoA reductase inhibitors. 1. An amine salt of pitavastatin or rosuvastatin , wherein said amine comprises at least one oxygen atom.2. The amine salt of wherein the amine comprises a compound selected from the group consisting of ethyldiethanol amine claim 1 , 2-furfuryl amine and 3-furfuryl amine.3. The amine salt of which is the 2-furfuryl amine salt of rosuvastatin.5. Use of an amine salt of in the preparation of amorphous or crystalline pitavastatin calcium salt or amorphous or crystalline rosuvastatin calcium salt. The present invention relates to oxygen-comprising amine salts of HMG-CoA reductase inhibitors, to a method of producing said amine salts and to the use of said amine salts in the production of pharmaceutically acceptable salts of HMG-CoA reductase inhibitors.HMG-CoA reductase inhibitors, also known as statins, are widely used drugs prescribed to treat hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis. Examples of HMG-CoA reductase inhibitors are atorvastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin.Production of HMG-CoA reductase inhibitors is known and includes (bio)-chemical conversion, chromatography, crystallization extraction, fermentation and the like. Some HMG-CoA reductase inhibitors, like lovastatin, are produced by fermentation using microorganisms of different species identified as species belonging to or genus. Some, like mevastatin, pravastatin and simvastatin, are obtained by treating the fermentation products using the methods of chemical or enzymatic synthesis. Others, like atorvastatin, fluvastatin, pitavastatin and rosuvastatin, are the products of total chemical synthesis.In several cases, production of HMG-CoA reductase inhibitors ...

Crystal form of quinoline compound and process for its production

A method for producing a drug substance of crystalline pitavastatin calcium excellent in stability, is presented. In the production of a compound (pitavastatin calcium) represented by the formula (1): The water content is adjusted to a level of from 5 to 15%, and the crystal form is controlled to be crystal form A, thereby to obtain a drug substance excellent in stability.

ANTIDIABETIC BICYCLIC COMPOUNDS

Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia. 2. The compound according to wherein T is CH; U is CR; V is CR; and W is CH; or a pharmaceutically acceptable salt thereof.4. The compound according to wherein X is N(R); or a pharmaceutically acceptable salt thereof.5. The compound according to wherein X is C(R)(R); or a pharmaceutically acceptable salt thereof.7. The compound according to wherein Z is C(R) claim 1 , provided that when X is C(R)(R) claim 1 , then Y is not C(R)(R); or a pharmaceutically acceptable salt thereof.8. The compound according to wherein Z is N claim 1 , provided that X is not N(R) claim 1 , and further provided that when X is C(R)(R) claim 1 , then Y is not C(R)(R); or a pharmaceutically acceptable salt thereof.10. The compound according to wherein A is aryl claim 1 , wherein aryl is unsubstituted or substituted with one to five substituents selected from R; or a pharmaceutically acceptable salt thereof.12. The compound according to wherein B is aryl claim 1 , wherein aryl is unsubstituted or substituted with one to five substituents selected from R; or a pharmaceutically acceptable salt thereof.14. The compound according to wherein Ris —Calkyl claim 1 , wherein alkyl is substituted with a substituent selected from Rand with one to three substituents selected from R; and{'sup': '2', 'Ris hydrogen;'}or a pharmaceutically acceptable salt thereof.15. The compound according to wherein Ris hydrogen; Ris hydrogen; Ris hydrogen; ...

CYSTEINYL LEUKOTRIENE ANTAGONISTS

The present invention relates to novel cysteinyl leukotriene (specifically LTD4) antagonists, mainly to quinolin, quinoxaline or benz[c]thiazole derivatives represented by the general formula (I), or the pharmaceutically acceptable salt thereof, process of preparation thereof, and to the use of the compounds in the preparation of pharmaceutical compositions for the therapeutic treatment of disorders related to cysteinyl leukotriene, in mammals, more specially in humans. 2. A compound according to claim 1 , wherein rings ‘a’ and ‘b’ comprise a fused hetero-cyclic aromatic ring system claim 1 , selected from a substituted or unsubstituted quinolin claim 1 , benzothiazole or a quinoxaline ring.3. A compound according to claim 1 , wherein the substitution pattern in the ring ‘c’ is (1 claim 1 , 2); (1 claim 1 , 3) or (1 claim 1 , 4) with respect to ‘Y’ and preferably (1 claim 1 , 3) as disclosed in the specification.4. A compound according to claim 1 , wherein W is —CH═.5. A compound according to claim 1 , wherein X is —CH═CH—.6. A compound according to claim 1 , wherein Y is —CH═CH—.7. A compound according to claim 1 , wherein Z represents a bond.8. A compound according to claim 1 , wherein Rand Rare selected from hydrogen and halogen.10. A compound according to claim 9 , wherein W is —CH═.11. A compound according to claim 9 , wherein X is —CH═CH—.12. A compound according to claim 9 , wherein Y is —CH═CH—.13. A compound according to claim 9 , wherein Z represents a bond.14. A compound according to claim 9 , wherein Rand Rare selected from hydrogen and halogen.15. A compound according to claim 9 , wherein A is —OR or —SR and P is selected from —O— claim 9 , —S— or —NR—.16. A compound according to claim 9 , wherein A is —NR— and P is selected from —O— claim 9 , —S— claim 9 , —NR— or —CH—.17. A compound according to wherein Q is a group selected from hydrogen claim 9 , OR claim 9 , —COOR claim 9 , —CONRR′ claim 9 , —CONHSOR claim 9 , —NHCO(CRR′)—COOR claim 9 , —C(R claim ...

SUBSTITUTED BICYCLIC COMPOUNDS

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): 116-. (canceled)19. The compound according to or a salt thereof claim 17 , wherein:{'sub': 2a', '2', '3', '3', '2', '5-6', '3', '2', '2', '3', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '2', '2', '4', '2', '2', '4', '3', '2', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '2', '2', '3', '3', '2', '1-3', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '2', '2', '1-2', '3', '2', '2', '2', '2', '2', '2-3', '2', '2', '3-4', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '3', '2', '2', '9', '3', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '3', '3', '2', '1-6', '3', '3', '2', '2', '3', '2', '2', '3', '3', '3', '2', '2', '2', '3', '3', '2', '3', '2', '2', '2', '2', '2', '2', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '3', '2', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '3', '2', '3', '2', '2', '2-4', '3', '2', '3', '2', '2', '2', '3', '2', '2', '2', '3', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '3', '2', '2', '2', '3', '3', '2', '2', '2', '1-2', '3', '2', '2', '2', '3', '2', '2', '3', '3', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '3', '2', '2', '2', '3', '3', '2', '2', '2', '2', '4', '3', '2', '2', '4', '3', '3', '2', '4', '3', '2', '3', '2', '5', '3', '2', '2', '4-7', '3', '2', '2', '2', '2-4', '3', '2', '2', '2', '3', '2', '2', '2', '2-3', '3', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2-3', '3', ' ...

ABUSE-RESISTANT LONG-ACTING RELEASE OPIOID PRODRUGS

There are provided, prodrugs of opioid such as levorphanol or morphine, having enhanced physical and chemical stability to resist tampering and to make long- acting release formulations, and pharmaceutically accepted salts and solvates thereof. There are also provided methods of using the disclosed compounds as abuse deterrent products. 2. The compound of or pharmaceutically acceptable salt thereof claim 1 , wherein Ris an unsubstituted straight or branched alkyl chain having 7-30 carbons.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris an unsubstituted straight alkyl chain having a formula of CH(CH)— claim 1 , wherein n is an integer of 8-24 (e.g. claim 1 , 10-24).4. The compound of or pharmaceutically acceptable salt thereof claim 3 , wherein Ris selected from CH(CH)— claim 3 , CH(CH)— claim 3 , CH(CH)— claim 3 , CH(CH)— claim 3 , and CH(CH)—.5. The compound of or pharmaceutically acceptable salt thereof claim 1 , wherein the alkyl claim 1 , alkenyl claim 1 , or alkynyl chain is optionally substituted with one or more groups independently selected from halogen claim 1 , optionally substituted Calkyl claim 1 , optionally substituted Cheteroalkyl with 1 or 2 heteroatoms independently selected from oxygen and nitrogen claim 1 , optionally substituted Calkenyl claim 1 , optionally substituted Calkynyl claim 1 , optionally substituted Ccycloalkyl claim 1 , optionally substituted Caryl claim 1 , optionally substituted 5-8 membered heterocycloalkyl claim 1 , optionally substituted 5-10 membered heteroaryl claim 1 , short peptides claim 1 , —NRR claim 1 , —C(═O)NRR claim 1 , —COOR claim 1 , and —OR claim 1 , wherein R claim 1 , R claim 1 , and Rare each independently hydrogen claim 1 , optionally substituted Calkyl claim 1 , optionally substituted Cheteroalkyl with 1 or 2 heteroatoms independently selected from oxygen and nitrogen claim 1 , optionally substituted Ccycloalkyl claim 1 , optionally substituted Caryl claim 1 , ...

ANTIDIABETIC TRICYCLIC COMPOUNDS

Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia. 4. The compound according to wherein n is 1; or a pharmaceutically acceptable salt thereof.5. The compound according to wherein Ris hydrogen; or a pharmaceutically acceptable salt thereof.6. The compound according to wherein X is oxygen; or a pharmaceutically acceptable salt thereof.7. The compound according to whereinT is selected from the group consisting of: CH and N;U is selected from the group consisting of: CH and N;V is selected from the group consisting of: CH and N; andW is selected from the group consisting of: CH and N,provided that one of T, U, V and W is N;or a pharmaceutically acceptable salt thereof.8. The compound according to wherein T is CH; U is CH; V is N; and W is CH; or a pharmaceutically acceptable salt thereof.9. The compound according to whereinA is a bicyclic aryl ring,{'sup': a', 'a', '8, 'sub': 1-6', '1-6, 'wherein each bicyclic aryl ring is unsubstituted or substituted with one to six substituents selected from R, and wherein two Rsubstituents together with the carbon atom to which they are attached may form a 3-6 membered cycloalkyl ring, or a 3-6 membered cycloheteroalkyl ring containing 0 to 3 heteroatoms independently selected from oxygen, sulfur, and NR, and wherein each 3-6 membered cycloalkyl and each 3-6 membered cycloheteroalkyl ring is unsubstituted or substituted with 1 to 4 substituents selected from: —Calkyl, —O—Calkyl, halogen and OH;'}or a ...

Green preparation method for quinoline compounds

Pharmaceutical and chemical intermediates and related chemistry providing a green preparation method for quinoline compounds. N-Substituted arylamine derivatives as raw material react with arylacetylene or arylethylene derivatives for 24 hours at 80° C.-160° C. in the presence of Brønsted acid catalyst and oxidant without solvent, to obtain quinoline compounds. Beneficial characteristics include convenient operation, mild reaction conditions, environmentally friendly property and possibility of realizing industrialization, and provides the quinoline compounds in high yields. The quinoline compounds synthesized by this method can be further functionalized into various compounds which have potential applications in development and research of natural products, functional materials and fine chemicals.

EBNA1 INHIBITORS AND THEIR METHOD OF USE

Pharmaceutical compositions of the invention comprise EBNA1 inhibitors useful for the treatment of diseases caused by EBNA1 activity such as cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis. Pharmaceutical compositions of the invention also comprise EBNA1 inhibitors useful for the treatment of diseases caused by latent Epstein-Barr Virus (EBV) infection. Pharmaceutical compositions of the invention also comprise EBNA1 inhibitors useful for the treatment of diseases caused by lytic Epstein-Barr Virus (EBV) infection. 4. The method of claim 1 , wherein the compound is at least one selected from the group consisting of:3-{2-[3-(methylsulfamoyl)phenyl]ethynyl}-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1H-indol-3-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(3-methanesulfonamidophenyl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;2-(1H-pyrrol-1-yl)-3-[2-(3-sulfamoylphenyl)ethynyl]benzoic acid;3-[2-(3-carbamoylphenyl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyridin-6-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(2-hydroxypyridin-4-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1H-indazol-6-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-{2-[3-(3,3-dimethyl-2-oxoazetidin-1-yl)phenyl]ethynyl}-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{3-[(2-carboxy-2,2-dimethylethyl)amino]phenyl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyrazin-3-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyridin-3-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyridin-5-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;2-(1H-pyrrol-1-yl)-3-(2-{1H-pyrrolo[2,3-b]pyridin-5-yl}ethynyl)benzoic acid;3-[2-(1-methyl-1H-indol-4-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1-methyl-1H-indol-5-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1-benzothiophen-6-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1H-indol-7-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-{2-[2-( ...

CHEMOSELECTIVE METHYLENE HYDROXYLATION IN AROMATIC MOLECULES

A chemoselective and reactive Mn(CF-PDP) catalyst system that enables for the first time the strategic advantages of late-stage aliphatic C—H hydroxylation to be leveraged in aromatic compounds. This discovery will benefit small molecule therapeutics by enabling the rapid diversification of aromatic drugs and natural products and identification of their metabolites. 2. The complex of wherein the complex is an (S claim 1 ,S) enantiomer.3. The complex of wherein the complex is an (R claim 1 ,R) enantiomer.4. The complex of wherein the complex is a salt and the anion of the salt is Cl claim 1 , Br claim 1 , AcO claim 1 , TfO claim 1 , CFCO claim 1 , BF claim 1 , ClO claim 1 , ReO claim 1 , AsF claim 1 , PF claim 1 , or SbF.5. The complex of wherein Land Lare each independently chloro claim 1 , acetone claim 1 , acetonitrile claim 1 , or a terminal oxo bridge; or Land Ltogether are a carboxylate group.6. The complex of wherein each Gand each Gis independently (C-C)alkyl substituted with one or more halo groups.7. The complex of wherein each Gis independently chloro claim 1 , methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , teat-butyl claim 1 , —OCH claim 1 , —C(═O)OCH claim 1 , —C(═O)OC(CH) claim 1 , —CF claim 1 , —CFCH claim 1 , or —CFCF.8. The complex of wherein each Gis independently chloro claim 7 , methyl claim 7 , ethyl claim 7 , isopropyl claim 7 , teat-butyl claim 7 , —OCH claim 7 , —C(═O)OCH claim 7 , —C(═O)OC(CH) claim 7 , —CF claim 7 , —CFCH claim 7 , or —CFCF.9. The complex of wherein x and y are each independently 2 or 3; or{'sup': 3', '4, 'wherein Gand Gare at the 4-position of the pyridyl moiety of Formula I.'}11. The complex of wherein each Gand each Gis independently chloro claim 10 , methyl claim 10 , ethyl claim 10 , isopropyl claim 10 , teat-butyl claim 10 , —OCH claim 10 , —C(═O)OCH claim 10 , —C(═O)OC(CH) claim 10 , —CF claim 10 , —CFCH claim 10 , or —CFCF.12. The complex of wherein z is 0.13. The complex of wherein Rand Rare each —CH—.15. The ...

METHODS FOR TREATING COGNITIVE DISORDERS USING 3-ARYL-3-HYDROXY-2-AMINO-PROPIONIC ACID AMIDES, 3-HETEROARYL-3-HYDROXY-2-AMINO-PROPIONIC ACID AMIDES AND RELATED COMPOUNDS

Disclosed herein are methods of treating a patient suffering from a cognitive disorder using compounds of Formulas 1 and 2 2. The use of claim 1 , wherein the sum of the integers m claim 1 , n and q is 3.3. The use of claim 2 , wherein one of the W claim 2 , X and Y groups is N.4. The use of claim 3 , wherein Rand Rtogether with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring.5. The use of claim 2 , wherein none of the W claim 2 , X and Y groups is a heteroatom.6. The use of wherein Rand Rtogether with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring.7. The use of claim 1 , wherein the sum of the integers m claim 1 , n and q is 2 and at least one of W claim 1 , X and Y is a heteroatom.8. The use of claim 7 , wherein only one of W claim 7 , X and Y represents a heteroatom.9. The use of claim 7 , wherein two of the W claim 7 , X and Y groups each represent an independently selected heteroatom.10. The use of claim 1 , wherein Ris H.11. The use of claim 10 , wherein both Rgroups are H.12. The use of claim 10 , wherein one Rgroup is H and the other Rgroup is CO—Ror alkyl of 1 to 20 carbons.13. The use of claim 10 , wherein Ris independently selected from H and alkyl of 1 to 10 carbons.14. The use of claim 1 , wherein Ris CO—R.15. The use of claim 1 , wherein Rand Rtogether with the nitrogen form a 4 claim 1 , 5 claim 1 , 6 or 7 membered ring.16. The use of claim 15 , wherein Rand Rtogether with the nitrogen form a 5 membered ring.17. The use of claim 15 , wherein Rand Rtogether with the nitrogen form a 6 membered ring.18. The use of claim 1 , wherein both Rand Rare hydrogen.20. The use of claim 19 , wherein Ris H.21. The use of claim 19 , wherein both Rgroups are H.22. The use of claim 19 , wherein both Rand Rare hydrogen.24. The use of claim 23 , wherein Ris H.25. The use of claim 23 , wherein both Rgroups are H.29. The use of claim 28 , wherein the sum of the integers m claim 28 , n and q is 3 ...

Kdm1a inhibitors for the treatment of disease

Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDM1A, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia.

GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO

GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: 129.-. (canceled)30. The compound that is 3-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propionic acid , or a pharmaceutically acceptable salt thereof.31. A pharmaceutical composition comprising the compound of claim 30 , or a pharmaceutically acceptable salt thereof claim 30 , and a pharmaceutically acceptable carrier or diluent.32. The compound that is 4-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-3-methyl-phenoxy)-butyric acid claim 30 , or a pharmaceutically acceptable salt thereof.33. A pharmaceutical composition comprising the compound of claim 32 , or a pharmaceutically acceptable salt thereof claim 32 , and a pharmaceutically acceptable carrier or diluent. This application is a continuation of U.S. patent application Ser. No. 15/210,470, filed Jul. 14, 2016, which is a continuation of U.S. patent application Ser. No. 14/592,690, filed Jan. 8, 2015, now issued as U.S. Pat. No. 9,422,310 on Aug. 23, 2016, which is a continuation of U.S. patent application Ser. No. 13/910,961 filed Jun. 5, 2013, now issued as U.S. Pat. No. 8,952,161 on Feb. 10, 2015, which is a continuation of U.S. patent application Ser. No. 13/293,943 filed Nov. 10, 2011, now issued as U.S. Pat. No. 8,481,738 on Jul. 9, 2013, which is a divisional of U.S. patent application Ser. No. 12/594,809, filed Feb. 22, 2010, now issued as U.S. Pat. No. 8,084,614 on Dec. 27, 2011, which application is a U.S. national stage application filed under 35 U.S.C. § 371 of International Patent Application No. PCT/US2008/059438, accorded an international filing date of Apr. 4, 2008, which claims the benefit of U.S. Provisional Application No. 60/910,621, filed Apr. 6, 2007, all of which applications are incorporated herein by reference in ...

Crystalline forms of pitavastatin calcium

The present invention is directed to new crystalline forms of Pitavastatin hemicalcium salt, referred to hereinafter as polymorphic Forms A, B, C, D, E and F, as well as the amorphous form. Furthermore, the present invention is directed to processes for the preparation of these crystalline forms and the amorphous form and pharmaceutical compositions comprising these crystalline forms or the amorphous forms.

NOVEL ADAMANTYL DERIVATIVES AS CANNABINOID RECEPTOR 2 AGONISTS

The invention relates to a compound of formula (I) 2. A compound according to claim 1 , wherein Ais —CH—.3. A compound according to claim 1 , wherein Ris -A-C(O)—Rand Ris hydrogen.4. A compound according to claim 1 , wherein Ais —CRR— or —NR—.5. A compound according to claim 1 , wherein{'sup': 18', '19, 'one of Rand Ris hydrogen and the other one is independently selected from tert-butylaminocarbonyl, hydroxymethyl, isopropyl, methoxy, ethoxy, isopropoxy, n-butoxy and methoxyethoxy;'}{'sup': 18', '19, 'or one of Rand Ris hydroxymethyl and the other one is isopropyl;'}{'sup': 18', '19', '4', '5, 'or Rand Rare both hydrogen at the same time, provided that Ris methoxycarbonyl or Ris methyl.'}6. A compound according to claim 1 , wherein one of Rand Ris hydrogen and the other one is methoxyethoxy or n-butoxy.7. A compound according to claim 1 , wherein Ris methyl or isopropyl.8. A compound according to claim 1 , wherein Rand Rare independently selected from hydrogen and methyl.9. A compound according to claim 1 , wherein Rand Rare independently selected from hydrogen and methyl.10. A compound according to claim 1 , wherein Ris hydrogen claim 1 , alkyl or alkoxy claim 1 , and R claim 1 , Rand Rare independently selected from hydrogen claim 1 , alkyl claim 1 , nitro claim 1 , fluoro claim 1 , chloro claim 1 , haloalkyl and alkoxy claim 1 , provided that R claim 1 , R claim 1 , Rand Rare not all hydrogen at the same time.11. A compound according to claim 1 , wherein Ris hydrogen claim 1 , nitro claim 1 , halogen claim 1 , alkyl or haloalkyl claim 1 , and R claim 1 , Rand Rare independently selected from hydrogen claim 1 , alkyl claim 1 , nitro claim 1 , fluoro claim 1 , chloro claim 1 , haloalkyl and alkoxy claim 1 , provided that R claim 1 , R claim 1 , Rand Rare not all hydrogen at the same time.12. A compound according to claim 1 , wherein Ris hydrogen claim 1 , halogen claim 1 , nitro or alkyl claim 1 , and R claim 1 , Rand Rare independently selected from hydrogen ...

BENZOCYCLOHEPTANE AND BENZOXEPINE DERIVATIVES

The present invention relates to a compound of formula (I) 2. The method as claimed in wherein A represents phenyl or phenyl substituted with 1 claim 1 , 2 or 3 Rsubstituents.4. The method as claimed in wherein A represents pyridyl claim 1 , pyrimidinyl or quinolinyl claim 1 , each of said pyridyl claim 1 , pyrimidinyl or quinolinyl optionally being substituted with 1 claim 1 , 2 or 3 Rsubstituents.5. The method as claimed in wherein Z represents CH.6. The method as claimed in wherein Z represents O.7. The method as claimed in wherein Rrepresents halo claim 1 , hydroxyl claim 1 , Calkyl or Calkyloxy.8. The method as claimed in wherein Rrepresents hydrogen.11. The method as claimed in wherein n represents an integer of value 1 or 2.12. The method as claimed in wherein n is 0.13. The method as claimed in wherein A represents phenyl claim 1 , 1 claim 1 ,3-benzodioxolyl claim 1 , 2 claim 1 ,3-dihydro-1 claim 1 ,4-benzodioxinyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , quinolinyl; each of said rings optionally being substituted with 1 or 2 substituents each independently selected from halo claim 1 , hydroxyl claim 1 , Calkyl or Calkyloxy; Rand Reach independently represent hydrogen claim 1 , Calkyl claim 1 , CalkyloxyCalkyl claim 1 , phenylCalkyl; or Rand Rare taken together with the nitrogen to which they are attached to form pyrrolidinyl optionally substituted in position 3 with hydroxyl; piperidinyl; morpholinyl; piperazinyl optionally substituted with Calkyl or Calkylcarbonyl; Rrepresents hydrogen or methyl.14. The method as claimed in wherein the substituents on the cycloheptane or oxepine ring have a cis configuration.15. The method as claimed in wherein the compound is an enantiomeric pure form.16. The method as claimed in wherein the compound is selected from(±) cis-6-(4-Chloro-3-methoxy-phenyl)-5-(3-diethylamino-propyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol oxalate;(±) cis-6-(3-Chloro-phenyl)-5-(3-diethylamino-propyl)-6,7,8,9-tetrahydro-5H- ...