СОЕДИНЕНИЯ, СПОСОБ ПОЛУЧЕНИЯ СОЕДИНЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Описывается соединение формулы (I) в свободной форме или в форме соли, где Ar обозначает группу формулы R1 обозначает водород или гидрокси, R2 и R3 каждый независимо друг от друга обозначает водород или С1-С4алкил, R4, R5, R6 и R7 каждый независимо друг от друга обозначает водород, С1-С4алкокси, C1-С4алкил или С1-С4алкил, замещенный С1-С4алкоксигруппой, или R5 и R6 вместе с атомами углерода, к которым они присоединены, обозначают 6-членное циклоалифатическое кольцо или 6-членное гетероциклическое кольцо, содержащее два атома кислорода, R8 обозначает -NHR13, где R13 обозначает водород, С1-С4алкил или -COR14, где R14обозначает водород, или R13 обозначает –SO2R17, где R17 обозначает С1-С4алкил, и R9 обозначает водород, или R8 обозначает -NHR18, где -NHR18 и R9 вместе с атомами углерода, к которым они присоединены, обозначают 6-членный гетероцикл, R10 обозначает -ОН, Х обозначает С1-С4алкил, Y обозначает углерод, n равно 1 или 2, p равно 1, q означает 1, r означает 0 или 1. Описывается также ...

НОВЫЙ СПОСОБ ПОЛУЧЕНИЯ СОЛИ

Изобретение относится к новому способу получения одной кристаллической полиморфной формы гидрогалогенида органического амина предпочтительно в сравнении с другой кристаллической полиморфной формой гидрогалогенида органического амина. Способ включает добавление триалкилсилилгалогенида к органическому амину в растворителе, где триалкилсилилгалогенид добавляется в условиях, в которых одна полиморфная форма кристаллизуется предпочтительно в сравнении с другой полиморфной формой, и где органический амин находится в форме свободного основания или кислотно-аддитивной соли. Причем, если органический амин находится в форме кислотно-аддитивной соли, сопряженная кислота кислотно-аддитивной соли является более слабой, чем гидрогалогеновая кислота, и растворитель представляет собой апротонный растворитель, а если органический амин находится в форме свободного основания, то он растворяется в апротонном растворителе, а триалкилсилилгалогенид добавляется в протонном растворителе. Органический амин представляет ...

2-ОКСО-3, 4-ДИГИДРОХИНОЛИНОВЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ РЕГУЛЯТОРОВ РОСТА РАСТЕНИЙ

Изобретение относится к новым сульфонамидным производным формулы (I), где R1 выбран из группы, состоящей из C1-С6алкила, C1-С6галогеналкила, С3-С6алкенила и С3-С5циклопропил-С1-С6-алкила; R2 выбран из группы, состоящей из водорода и С1-С4алкила; R3 выбран из группы, состоящей из водорода, галогена и C1-С4алкила; R7 и R8 независимо выбраны из группы, состоящей из водорода, галогена, циано, С1-С4алкила, С2-С4алкенила, С2-С4алкинила, C1-С4алкокси, С1-С4галогеналкила, С1-С4галогеналкокси и С3-С4циклоалкила; R4 и R5 независимо выбраны из группы, состоящей из водорода, С1-С4алкила, С1-С4галогеналкила и С3-С4циклоалкила; или R4 и R5 могут образовывать вместе с атомом или атомами, к которым они непосредственно присоединены, С3-С4циклоалкил или С4гетероциклил; R6 представляет собой водород; L выбран из группы, состоящей из связи, линейной -С1-С4-алкильной цепи, линейной -С2-С4-алкенильной цепи и линейной -С2-С4-алкинильной цепи; А представляет собой водород, С1-С7алкил, С3-С5циклоалкил, 3-10-членный ...

СОЛЬ, ОБРАЗОВАННАЯ ИЗ АМИНА И ПРОИЗВОДНОГО КАРБОСТИРИЛА

Изобретение относится к соли амина с производным карбостирила, образованной из производного карбостирила, представленного формулой (1), R означает атом галогена, положением замещения боковой цепи является 3- или 4-положение в скелете карбостирила, и связывание между 3- и 4-положениями скелета карбостирила осуществляется посредством простой связи или двойной связи, и амина, выбранного из: аминокислоты; C1-6 алкилзамещенного амина, который может иметь заместитель, выбранный из группы, включающей гидроксигруппу и аминогруппу; и аминосахара, которая превосходно растворяется в воде. Также изобретение относится к фармацевтической композиции, содержащей в качестве активного ингредиента соль амина с производным карбостирила формулы (I). Технический результат: получены новые соли, обладающие полезными биологическими свойствами. 3 н. и 22 з.п. ф-лы.

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

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

СПОСОБ ПОЛУЧЕНИЯ Е-ИЗОМЕРОВ ПРОИЗВОДНЫХ АКРИЛОВОЙ КИСЛОТЫ

Использование: в качестве фунгицидов в сельском хозяйстве. Сущность изобретения: продукт: Е - изомеры производных акриловой кислоты общей формулы , где W - пиридинил- или пиримидинилгруппа, замещенная галогеном, C1-C4 -алкилом, который, в свою очередь, может быть замещен гомогеном, фенилом; C1-C4 -алкоксилом, феноксигруппой, которая может быть замещена 1-метоксикарбонил-2-метоксиэтенилом, галогеном, циано- или нитрогруппой, амино-, формамидо-, нитро-, циано- или N-оксидной группой, или W-хинолинил- или хиназолинилгруппа, возможно замещенная галогеном, и связанные с А одним из атомов углерода цинка, А - кислород или группа S(O)n , где n=0, или 1, или 2 при условии, что когда W - 5-трифторметилпиридинил-2, то А не является кислородом. Реагент 1: соединение общей формулы . Реагент 2: W - L, где L - галоген. Условия процесса: в присутствии основания в органическом растворителе, возможно в присутствии катализатора из числа переходного металла или его соли. 9 табл.

[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 ...

ПРОИЗВОДНЫЕ ФЕНЭТАНОЛАМИНА ДЛЯ ЛЕЧЕНИЯ РЕСПИРАТОРНЫХ ЗАБОЛЕВАНИЙ

... 1. Соединение формулы (I) или его соль, сольват или физиологически функциональное производное, где m представляет собой целое число от 2 до 8; и n представляет собой целое число от 3 до 11; при условии, что m+n составляет число от 5 до 19; R1 представляет собой SR6, SOR6 или SO2R6, где R6 представляет собой С3-7 циклоалкильную или С3-7циклоалкенильную группу; R2 и R3 независимо выбраны из водорода, С1-6алкила, С1-6алкокси, галогено, фенила и С1-6галогеноалкила; R4 и R5 независимо выбраны из водорода и С1-4алкила, при условии, что общее количество атомов углерода в R4 и R5 не превышает 4; Ar представляет собой группу, выбранную из где R8 представляет собой водород, галоген, -(CH2)qOR11, -NR11C(O)R12, -NR11SO2R12, -SO2NR11R12, -NR11R12, -OC(O)R13 или OC(O)NR11R12, и R7 представляет собой водород, галоген или С1-4алкил; или R8 представляет собой -NHR14, и R7 и -NHR14 вместе образуют 5- или 6-членное гетероциклическое кольцо; R9 представляет собой водород, галоген, -OR11 или -NR11R12; R10 представляет ...

АРИЛАНИЛИНОВЫЕ АГОНИСТЫ БЕТА2 АДРЕНЕРГИЧЕСКИХ РЕЦЕПТОРОВ

... 1. Соединение формулы (I) где каждый из R1-R5 независимо выбран из группы, включающей водород, алкил, алкенил, алкинил, арил, гетероарил, циклоалкил, гетероциклил и Ra; или R1 и R2, R2 и R3, R3 и R4 или R4 и R5 объединены вместе с образованием группы, выбранной из группы, включающей -С(Rd)=C(Rd)С(=O)NRd-, -CRdRd-CRdRd-C(=O)NRd-, -NRdC(=O)C(Rd)=C(Rd)-, -NRdC(=O)CRdRd-CRdRd-, -NRdC(=O)S-, -SC(=O)NRd-, -(CRdRd)p-, -S(CRdRd)q-, -(CRdRd)qS-, -S(CRdRd)rO-, -O(CRdRd)rS- и -NHC(Rj)=C(Rk)-; R6 представляет собой водород, алкил или алкокси; R7 представляет собой водород или алкил; R8 представляет собой водород или алкил; или R8 вместе с R9представляет собой -CH2- или -СН2СН2-; R9 независимо выбран из группы, включающей алкил, алкенил, алкинил, арил, гетероарил, циклоалкил, гетероциклил и Ra, или R9вместе с R8 представляет собой -CH2 - или -СН2СН2-; R10 представляет собой водород или алкил; R11, R12 и R13 независимо выбраны из группы, включающей водород, алкил, циклоалкил, алкенил, алкинил, арил, ...

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

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

КРИСТАЛЛИЧЕСКИЕ ФОРМЫ БЕДАКВИЛИН ФУМАРАТА И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

2-АМИНОБЕНЗАМИДНОЕ ПРОИЗВОДНОЕ

... 1. Ингибитор активации VR1, который включает 2-аминобензамидное производное общей формулы (I) или его соль в качестве активного ингредиента ! ! где - бензольное кольцо или пиридиновое кольцо, ! R3 - одинаковые или отличные друг от друга и каждый представляет собой H, галоген, галоген-низший алкил, циано, нитро, низший алкил, -NR4R5, -низший алкилен-NR4R5, -низший алкилен-NR6-CO2-низший алкил, -O-низший алкил, -O-галоген-низший алкил, фенил или тиенил, ! m - 1, 2 или 3, ! R4 и R5 - одинаковые или отличные друг от друга и каждый представляет собой H или низший алкил, где R4 и R5 могут быть объединены со смежным атомом азота с образованием моноциклического азотсодержащего насыщенного гетерокольца, которое может быть замещено низшим алкилом или группой низший алкилен-OH, ! R6 - H или низший алкил, !- моноциклическое гетерокольцо, циклоалкен или бензольное кольцо, ! где кольцо, представленное как А, может быть замещено 1-4 группами, выбранными из групп -OH, -низший алкилен-OH, -низший алкилен-NR4R5 ...

АМИННЫЕ ПРОИЗВОДНЫЕ И ИХ ПРИМЕНЕНИЕ В БЕТА-2-АДРЕНОРЕЦЕПТОР-ОПОСРЕДОВАННЫХ ЗАБОЛЕВАНИЙ

... 1. Соединение формулы (I) !! где Ar представляет собой: ! ! ! каждый из R2, R3, R4, R5, R4′ и R5′ независимо представляет собой водород или C1-6алкил; ! А представляет собой СН2, С(O) или S(O)2; ! D представляет собой кислород, серу или NR8; ! Е представляет собой связь, CR63R64, CR63R64CR65R66, CR63R64CR65R66CR67R68 или CR63CR64CR65R66CR67R68CR69R70; ! R63 и R64 независимо представляет собой водород, С1-4алкил; и когда D представляет собой кислород, R63 и R64 также могут представлять собой фторо; ! R65, R66, R67, R68, R69 и R70 независимо представляют собой водород, фторо или С1-4алкил; ! k равно 0 или 1; ! m означает целое число от 0 до 3; ! R6 представляет собой группу -(X)p-Y-(Z)q-R10, или R6 представляет собой α- или β-разветвленный С3-12алкил (возможно замещенный галогеном, C1-6алкокси, С1-6алкилтио, С1-6алкилS(O), С1-6алкилS(O)2, C1-6галогеноалкокси, гидрокси, NR58R59, ОС(O)(С1-6алкил), С3-12циклоалкилом или R60); ! Х и Z независимо представляют собой С1-6алкиленовую группу, возможно ...

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 ...

Способ получения карбостириловыхпРОизВОдНыХ

Способ борьбы с вредными насекомыми

Способ получения карбостириловыхили ОКСиНдОлОВыХ пРОизВОдНыХ

Способ получения карбостирильных производных или их фармацевтически приемлемых солей

Способ получения карбости- рильных производных общей формулы (I) К «г R, где R, - водород, низщая алкильная группа, низшая алкенильная группа, низшая алкинильная группа или фенил- (низшая) алкильная группа; Rj - водород, низшая алкильнай группа, низшая алкоксильная группа, галоген или гидроксильная группа; Rg - водород или низшая алкильная группа; R и Rj - одинаковые или различные , каждый водород, галоген, низшая алкильная группа, гидроксильная группа, низшая алкоксильная группа или нитрогруппа; связь между положениями 3 и 4 в карбостирильном ядре - одинарная или двойная; положение, в котором имидазопири- дильная группа общей формулы К Т.соединена с карбостирильным ядром, - 5 или 6; при условии, что, когда имидазо- пиридильная группа соединена с карбостирильным ядром в положении 5, Rj не должен представлять собой водород , низшую алкильную группу или галоген; или их фармацевтически приемлемых солей, отличающийся тем, что соединение общей формулы (II) « сд 3d О где Х - галоген, R,, Rj , ...

Способ получения карбостирильных производных

Способ получения амидных производных хинолина или их солей с кислотами

Изобретение касается гетероциклических соединений , в частности, способов получения амидных производных хинолина общей формулы X-O-CH2-C(O)- NR1R2, где X-группа формулы @ где V и W (одинаковые или разные) - H, галоид, C1-C4-алкокси, NH2или C1-C4-ациламиногруппа Z - тиенил, пиридил или фенил (он может быть замещен одним или двумя заместителями, выбранными из группы: галоид, C1-C4-алкил, C1-C4-алкокси, CF3, NO2или NH2) R1-H- или изо-C1-C6-алкил, C1-C4- алкокси- C1-C4-алкил, C3-C6-циклоалкил, фенил, фенил-C1-C4-алкил, C3-C6-циклоалкил-C1-C3-алкил, 4-морфолиновый цикл, или NR1R2- пирролидиновый цикл, пиперидиновый цикл (он может быть замещен гидроксилом, C1-C4-алкилом, C1-C4-алкокси, C1-C4-алкоксикарбонилом), морфолиновый цикл (он может быть замещен одной или двумя C1-C4-алкильными группами), тиоморфолиновый цикл, пиперазиновый цикл (он может быть замещен у атома азота C1-C4-алкилом, C1-C4-алкилоксикарбонилом, C2-C5-ацилом, формилом), пиперазиноновый цикл (он может быть замещен у атома азота ...

BETA-ADRENERGISCHE REZEPTOREN-BLOCKER

Antidiabetikum

HETEROCYCLIC DERIVATIVES OF GUANIDINE, THEIR PREPARATION AND PHARMACEUTICAL FORMULATIONS COMPRISING THEM

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

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

VERFAHREN ZUR HERSTELLUNG VON L-ALKOXYCARBONYL-2-ALKOXY-L,2-DIHYDROCHINOLINEN

Fungizide

DERIVATIVES OF BICYCLIC AMINO ACIDS, PROCESSES FOR THEIR PREPARATION, AGENTS CONTAINING THEM AND THEIR USE AS WELL AS BICYCLIC AMINO ACIDS AS INTERMEDIATES AND PROCESS FOR THEIR PREPARATION

VERFAHREN ZUR HAERTUNG PHOTOGRAPHISCHER SCHICHTEN

DIAMINDERIVATE UND PHARMAZEUTISCHE ZUSAMMENSETZUNGEN DIE DIESE ENTHALTEN

NEUE BENZAMIDE ALS PPATY-MODULATOREN

FUNGICIDES

Medicaments

SILVER HALIDE PHOTOFRAPHIC LIGHT-SENSITIVE MATERIAL HAVING AN ANTISTATIC LAYER

SULPHIMINES

Estrogen receptor modulators and use thereof

Triphenylene derivative compounds of formula (I): wherein X1 and X2 are CH, CR3 or N; Z is -OH or â O-C1-6 alkyl; R2 is C1-4 alkyl, C1-4 fluoroalkyl, C1-4 deuteroalkyl, C3-6 cycloalkyl or C1-4 alkylene-W, where W is hydroxyl, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy or C3-6 cycloalkyl; R3-R5 are halogen, C1-4 alkyl or other substituents; R6 and R7 are H, C1-4 alkyl or halogen; m is 0-2; n is 0-4; and p is 0-2; may be useful as estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds of formula (I). These compounds may be useful for the treatment of conditions that are mediated by or dependent upon estrogen receptors. Such diseases include cancer, for example breast, ovarian, endometrial, prostate and uterine cancers, and also cardiovascular disease and conditions such as Parkinsonâ s disease and dementia.

Aripiprazole type I microcrystal, aripiprazole solid preparation, and preparation method

CARBOSTYRIL DERIVATIVES PROCESSES FOR THEIR PRODUCTION AND ANTIHISTAMINIC AGENTS CONTAINING THEM

Octahydro pyrazolo (3,4-g) quinolines

Octahydropyrazolo?3,4-g!quinolines, dopamine agonists, useful in treatment of Parkinsonism and in inhibiting secretion of prolactin.

6(OXO-OR HYDROXY-)DECAHYDROQUINOLINES

Estrogen receptor modulators and uses thereof

Substituted quinolizines and preparation thereof

The invention comprises novel compounds of formulae wherein R1 and R2 represent hydrogen, hydroxy or lower alkoxy, R3 represents hydrogen or lower alkyl, R4 represents hydrogen, lower alkyl, alkoxy, alkenyl or alkynyl, R5 represents hydrogen, hydroxy, carboxylic acyloxy, alkoxy, -COCH3, -COCH2OH, -COOH, -COOR11, where R11 is lower alkyl, -COCl, or -CONR6R7, where each of R6 and R7 is hydrogen or lower alkyl, or R6 and R7 together with the nitrogen atom to which they are attached form a heterocyclic ring, or R4 and R5 together with the carbon atom to which they are attached form a keto or cyclic ketal group, and Z is an anion, and the non-toxic, pharmaceutically acceptable acid addition salts of the free bases. The compounds may be prepared by refluxing ...

METHOD OF HARDENING PHOTOGRAPHIC LAYERS

... 1452669 Alkoxy (iso)quinoline esters AGFAGEVAERT AG 24 June 1974 [26 June 1973] 27851/74 Heading C2C [Also in Division G2] Quinoline and isoquinoline derivatives for use as photographic hardeners are prepared as follows: (a) 2-ethoxy-1(2H)-quinoline carboxylic acid ethyl ester is obtained by reacting quinoline with ethyl chloroformate 1-ethoxy-2- ethoxycarbonyl-1,2-dihydroisoquinoline is prepared analogously; (b) ethyl chloroformate and quinoline are reacted with aqueous KOH solution to give a mixture of 2-hydroxy-N- carbethoxy - 1,2 - dihydroquinoline and di- (N - carbethoxy - 1,2 - dihydro - 2 - quinolyl)- ether ("preparation A"); (c) this preparation is reacted with isopropanol, n-butanol and benzyl alcohol, respectively, in ether, in the presence of BF 3 etherate to give the 2-isopropoxy-, 2- butoxy and 2-benzyloxy-N-carbethoxy-1,2-dihydroquinolines.

PIPERAZINYLBENZOHETEROCYCLIC COMPOUNDS

PREPARATION OF BENZOPHENONES

... 1454684 Benzophenones UPJOHN CO 7 Feb 1974 [14 Feb 1973] 23402/76 Divided out of 1454682 Heading C2C Benzophenones are prepared by the following route CR 1 = H, C 1-3 alkyl, Ph, PhCH 2 , C 2-4 alkoxycarbonyl; R 2-5 =H, halogen, CF 3 , CN, NO 2 , di(C 1-3 alkyl)amino, C 1-3 alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl or alkanoylamino; X = activating atom or group; Ac= acetyl).

SUBSTITUTED AZETIDINOLS

2-CHLOROQUINOLINES AND THEIR USE AS COCCIDIOSTATS

... 1508738 2 - Chloro - quinoline - derivatives IMC CMEMICAL GROUP Inc 29 July 1976 [6 Aug 1975] 45296/77 Divided out of 1508737 Heading C2C Novel compounds of the Formula I wherein R is 5-chloro and R1 is H or R is 7- chloro and R1 is phenyl, may be prepared by reacting a compound II with phosphorous oxychloride. The compound II in which R is 7-chloro and R1 is phenyl is among the compounds claimed per se in parent Specification. Compositions of the compound I may be administered orally to poultry to combat coecidiosis. The composition is in the form of poultry feed.

Quinoline derivatives and use thereof as mycobacterial inhibitors

Antibacterial quinoline derivatives

Antibacterial quinoline derivatives

Method of modulating stress-activated protein kinase system

Quinoline derivatives and their use as mycobacterial inhibitors.

FUNGICIDES

Novel herbicides.

COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS

Novel rebamipide prodrugs, preparation method and use thereof

Fungicides

Compounds useful as fungicides ...

Antibacterial quinoline derivatives.

Quinoline derivatives as antibacterial agents.

Antibacterial quinoline derivatives

Quinoline derivatives as antibacterial agents

Antibacterial quinoline derivatives

Quinoline derivatives and use thereof as mycobacterial inhibitors.

Antibacterial quinoline derivatives

Quinoline derivatives and their use as mycobacterial inhibitors.

Antibacterial quinoline derivatives

Fumarate salt of (ALPHA S, BETA R)-6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-1-naphthalenyl-beta-phenyl-3-quinolineethanol

Quinoline derivatives as antibacterial agents

Caspase inhibitors and uses thereof.

This invention provides novel compounds, and pharmaceutically acceptable derivatives thereof, that are useful as caspase inhibitors. These compounds have the general formula (I): where R1, R2, and R3 are as described (I) herein, Ring A contains zero to two double bonds, each X is independently selected from nitrogen or carbon, at least on X is Ring A is a nitrogen, Ring A is optionally substituted as described, and may be fused to a saturated or unsat-urated five to seven membered ring containing zero to three heteroatoms, and provided that when X is a carbon, a substituent on X3 is attached by an atom other than nitorgen.

Quinoline derivatives as antibacterial agents.

FUNGICIDES

Substituted benzolactam compounds.

This invention relates to compounds of general formula (i); or pharmaceutically acceptable salt threof, w, t, y, x, q, r1, r2, and r3 are adefined herein. This invention also relates to compounds of formula (i), depicted above, wherein y is -nh-; t is(2s,3s)-2-phenylpiperridin-3-yl where the phenyl group of said (2s, 3s)-2-phenylpiperridine-3-yl may optionally be substituted with fluro; q is oxygen and is double bonded to the carbon atom to which it is attached, x is methoxy or ethoxy, r1 is hydrogen, methyl or halo-c1-c2 alkyl, w is methylene, ethylene or vinylene; r2 and r3 are independently hydrogen or methyl, or one fo r2 or r3 may be hydroxy, when w is ethylene, r2 and r3 are both methyl, when w is methylene, and r2 and r3 are both hydrogen, when vinylene. The invention is further directed to methods of treating vasrious cns and other disorders using said compounds and pharmaceutical compositions.

Quinoline derivatives as antibacterial agents

Piperazine derivatives for the treatment of HIV infections.

Antibacterial quinoline derivatives

Antibacterial quinoline derivatives

Antibacterial quinoline derivatives

Quinoline derivatives and use thereof as mycobacterial inhibitors

Quinoline derivatives as antibacterial agents

Fumarate salt of (ALPHA S, BETA R)-6-bromo-alpha-[2-(dimethylamino) ethyl]-2-methoxy-alpha-1-naphthalenyl-beta-phenyl-3-quinolineethanol

Quinoline derivatives and their use as mycobacterial inhibitors.

Method of modulating stress-activated protein kinase system

HETEROBICYCLIC COMPOUNDS AND THEIR USE FOR THE TREATMENT OF TUBERCULOSIS

Antibacterial quinoline derivatives

2-Quinolinyl-acetic acid derivatives as HIV antiviral compounds

Substituted benzolactam compounds

Derived from triazine, proceeded for their pharmaceutical preparation, and compositions comprising these derivatives.

Pesticides

Substituted benzolactam compounds.

NR, N-dialkylaminocarbamates of derived from hydroxypyridine substituted.

Piperazine derivatives for the treatment of HIV infections.

Saturated tricyclic-nitrogen-containing diones as cognition activators.

Caspace inhibitors and uses thereof

Quinoline derivatives and their use as mycobacterial inhibitors.

Novel rebamipide prodrugs, preparation method and use thereof

Fumarate salt of (ALPHA S, BETA R)-6-bromo-alpha-[2-(dimethylamino) ethyl]-2-methoxy-alpha-1-naphthalenyl-beta-phenyl-3-quinolineethanol

Antibacterial quinoline derivatives

Estrogen receptor modulators and uses thereof

Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

Selective inhibitors of cb2 receptor expression and/or activity for the treatment of obesity and obesity-related disorders

The invention relates to a method for treating and/or preventing obesity and/or obesity-related disorders by administering to a subject in need thereof a selective inhibitor of cannabinoid type 2 (CB2) receptor expression.

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:

Quinolines and Their Therapeutic Use

Compounds of formula (I) are CRTH2 ligands, useful in the treatment of, for example, asthma and COPD wherein: R 1 is halogen or cyano; R 2 is hydrogen or methyl; R 3 and R 4 are independently —OR 6 , C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, the latter two groups being optionally substituted by one or more halogen atoms; R 5 is hydrogen or halogen; R 6 is C 1 C 6 alkyl or C 3 -C 6 cycloalkyl, either of which being optionally substituted by one or more halogen atoms; X is —CH 2 —, —S—, or —O—; one of Y and Y 1 is hydrogen and the other is OR 6 , —C(═O)R 7 , NR 8 SO 2 R 6 or a heterocyclic group selected from those referred to in the specification; and R 6 , R 7 and R 8 are as defined in the specification.

Viral polymerase inhibitors

Compounds of formula I: wherein X, R 2 , R 3 , R 3a , R 3b , R 5 and R 6 are defined herein, are useful as inhibitors of the hepatitis C virus NS5B polymerase.

Low hygroscopic aripiprazole drug substance and processes for the preparation thereof

The present invention provides low hygroscopic forms of aripiprazole and processes for the preparation thereof which will not convert to a hydrate or lose their original solubility even when a medicinal preparation containing the anhydrous Aripiprazole crystals is stored for an extended period.

FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS

The present invention relates to sodium channel inhibitors of Formula I: 2. The compound of claim 1 , wherein Xand Xare both —CH═.3. The compound of claim 2 , wherein Ris hydrogen or alkyl of 1-6 carbon atoms optionally substituted by hydroxy claim 2 , —C(O)R claim 2 , trifluoromethyl claim 2 , alkoxy of 1-6 carbon atoms claim 2 , or phenyl optionally substituted by —C(O)R.4. The compound of claim 3 , wherein R claim 3 , R claim 3 , and Rare hydrogen or lower alkyl of 1-6 carbon atoms.5. The compound of claim 4 , wherein Ris phenyl optionally substituted by 1 or 2 substituents independently selected from halo claim 4 , trifluoromethyl claim 4 , trifluoromethoxy claim 4 , cyano claim 4 , or —C(O)R claim 4 ,6. The compound of claim 5 , wherein Ris hydrogen claim 5 , R claim 5 , R claim 5 , R claim 5 , and Rare hydrogen claim 5 , Ris methoxy claim 5 , and Ris 6-(4-chlorophenyl) claim 5 , namely 6-(4-chlorophenyl)-7-methoxy-3 claim 5 ,4-dihydroquinolin-2(1H)-one.7. The compound of claim 5 , wherein Ris 2-methoxyethyl claim 5 , R claim 5 , R claim 5 , R claim 5 , Rand Rare hydrogen claim 5 , and Ris 6-(4-trifluoromethylphenyl) claim 5 , namely 1-(2-methoxyethyl)-6-(4-(trifluoromethyl)phenyl)-3 claim 5 ,4-dihydroquinolin-2(1H)-one.8. The compound of claim 5 , wherein Ris carboxymethyl claim 5 , R claim 5 , R claim 5 , R claim 5 , Rand Rare hydrogen claim 5 , and Ris 6-(4-trifluoromethoxyphenyl) claim 5 , namely 2-(2-oxo-6-(4-(trifluoromethoxy)phenyl)-3 claim 5 ,4-dihydroquinolin-1(2H)-yl)acetic acid.9. The compound of claim 5 , wherein Ris hydrogen claim 5 , R claim 5 , R claim 5 , R claim 5 , Rand Rare hydrogen claim 5 , and Ris 6-(3-fluorophenyl) claim 5 , namely 6-(3-fluorophenyl)-3 claim 5 ,4-dihydroquinolin-2(1H)-one.10. The compound of claim 5 , wherein Ris benzyl claim 5 , R claim 5 , R claim 5 , R claim 5 , Rand Rare hydrogen claim 5 , and Ris 6-(2 claim 5 ,4-difluorophenyl) claim 5 , namely 1-benzyl-6-(2 claim 5 ,4-difluorophenyl)-3 claim 5 ,4-dihydroquinolin-2( ...

ACTIVATORS OF HUMAN PYRUVATE KINASE

Disclosed are pyruvate kinase M2 activators which are compounds of Formula (I), including those of Formula (II), wherein A, A, L, R, Rto R, Xto X, k, n, and m are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer. A-NR-L-A(I). 2. (canceled)3. The compound or salt of claim 1 , wherein the phenyl ring of the bicyclic ring of R′ is fused with an aryl claim 1 , a heteroaryl claim 1 , a cyclyl claim 1 , or a heterocyclyl claim 1 , each of which is optionally substituted with one or more substituents selected from the group consisting of aryl claim 1 , heteroaryl claim 1 , cyclyl claim 1 , alkyl claim 1 , alkoxyl claim 1 , halogen claim 1 , NH claim 1 , NH—(C-C)alkyl claim 1 , N—(C-C)alkyl-(C-C)alkyl claim 1 , (C-C)alkyl-OC— claim 1 , and heterocyclyl claim 1 , each of which other than halogen and NHis further optionally substituted with one or more substituents selected from the group consisting of NH claim 1 , OH claim 1 , NH—(C-C)alkyl and N—(C-C)alkyl-(C-C)alkyl.4. The compound or salt of claim 1 , wherein the cyclyl or heterocyclyl of R′ or R″ is a five-membered claim 1 , six-membered claim 1 , or seven-membered ring.5. The compound or salt of claim 1 , wherein the heterocyclyl contains one or two heteroatoms.6. The compound or salt of claim 1 , wherein R is methyl or H.8. The compound or salt of claim 7 , wherein one Ris at the ortho position relative to the carbon attached to the NR-L moiety.9. The compound or salt of claim 7 , wherein one Ris H claim 7 , F claim 7 , Cl claim 7 , Br claim 7 , methyl claim 7 , N(Me) claim 7 , NHMe claim 7 , 1-piperidinyl claim 7 , 2-(dimethylamino)ethyl)(methyl)amino claim 7 , pyrrolidin-1-yl claim 7 , 3-(dimethylamino)pyrrolidin-1-yl claim 7 , 2-hydroxy-2-methylpropylamino claim 7 , isopropylamino claim 7 , diethylamino claim 7 , 1-hydroxypropan-2-ylamino claim 7 , 2-hydroxyethylamino claim 7 , or phenyl.10. The compound or salt of claim 1 , wherein ...

Process for making sterile aripiprazole of desired mean particle size

A process is provided for making sterile aripiprazole having an average particle size less than 100 microns but preferably greater than 25 microns employing an impinging jet crystallization procedure. The resulting bulk aripiprazole of desired particle size may be used to form a sterile freeze-dried aripiprazole formulation, which upon constitution with water and intramuscular injection releases aripiprazole over a period of at least about one week and up to about eight weeks.

FLUOROPHORE CHELATED LANTHANIDE LUMINESCENT PROBES WITH IMPROVED QUANTUM EFFICIENCY

The invention relates to novel luminescent compositions of matter containing a fluorophore, synthetic methods for making the compositions, macromolecular conjugates of the compositions, and the use of the compositions in various methods of detection. The invention also provides kits containing the compositions and their conjugates for use in the methods of detection. 161.-. (canceled)63. The composition of claim 62 , wherein Ris selected from the group consisting of CF claim 62 , CH claim 62 , and O—CHCH.64. The composition of claim 62 , wherein Ris selected from the group consisting of O—CHCHand O—(CH)—N.65. The composition of claim 62 , wherein Ris selected from the group consisting of H claim 62 , CHC(O)NH—(CH)—N═C═S claim 62 , and CHC(O)NH—(CH)—NHC(O)CHBr.69. The composition of claim 62 , wherein Ris selected from the group consisting of CH claim 62 , CF claim 62 , CHC(O)NH—(CH)—N═C═S claim 62 , and CHC(O)NH—(CH)—NHC(O)CHBr.70. The composition of claim 62 , wherein Ris selected from the group consisting of H and CHC(O)NH—(CH)—N═C═S claim 62 , and CHC(O)NH—(CH)—NHC(O)CHBr.74. The luminescent probe composition of claim 62 , wherein the chelating moiety is selected from the group consisting of EDTA claim 62 , DTPA claim 62 , TTHA claim 62 , DOTA claim 62 , TAGA claim 62 , DOTP claim 62 , DTPA-BMA claim 62 , DO2P claim 62 , and HP-DO3A.75. The composition of further comprising a metal ion chelated to the chelating moiety claim 62 ,wherein the metal is a lanthanide selected from the group consisting of: Gd(III), Dy(III), Ho(III), Er(III), Eu(III), Tb(III), Sm(III), Ce(III), Pr(III), Yb(III), Tm(III), Nd(III), and Tb(IV).76. The composition of claim 62 , wherein the composition is conjugated to a macromolecule claim 62 ,wherein the macromolecule is selected from the group consisting of a polypeptide and a peptide aptamer with binding affinity to a predetermined peptide target.77. The composition of claim 76 , wherein the macromolecule is a polypeptide selected from ...

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).

CHIRAL COMPOUNDS, COMPOSITIONS, PRODUCTS AND METHODS EMPLOYING SAME

Compounds that function, alone or in combination, as inhibitors of pigmentation for the improvement of mammalian skin are described herein. Specifically, the compounds of the present disclosure, namely chiral, non-racemic compounds, function as pigment formation inhibitors thereof to beautify skin and discourage the production of melanins. One or more products, consumer and otherwise, comprising the chiral, non-racemic compounds are disclosed herein. Methods of employing both the compounds of the present disclosure and the products incorporating the present compounds are also disclosed herein. 15. A composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) from about 0.0001% to about 99.999% of a compound according to formula (I) of ;'}{'claim-ref': {'@idref': 'CLM-00008', 'claim 8'}, '(b) from about 99.999% to about 0.0001% of a compound according to formula (II) of ; and'}(c) optionally, a pharmaceutically acceptable carrier,{'sup': 1', '2', '1, 'claim-ref': [{'@idref': 'CLM-00001', 'claim 1'}, {'@idref': 'CLM-00008', 'claim 8'}], 'wherein at least one of the substituents X, X, A, B, Z and Rin the compound according to formula (I) of is different from the corresponding substituent in the compound according to formula (II) of .'}16. A product comprising a compound according to .1722-. (canceled)2318. The product according to claim claim 1 , wherein said product is a skin care composition.24. The product according to claim 23 , further comprising a dermatologically acceptable carrier.25. (canceled)26. (canceled)27. A method of lightening mammalian skin claim 1 , said method comprising topically applying a compound according to to an area of skin in need of treatment.2831-. (canceled)32. A product comprising a compound according to .33. The product according to claim 32 , wherein said product is a skin care composition.34. The product according to claim 33 , further comprising a dermatologically acceptable carrier.35. A method of lightening ...

SKIN LIGHTENING COMPOSITIONS

Compositions and methods for lightening mammalian skin are described herein. 2. The composition of claim 1 , wherein Z is O.3. The composition of claim 1 , wherein A and B are taken together with the atoms to which they are attached to form an optionally substituted ring having from 4-9 member atoms.4. The composition of claim 1 , wherein A and B are taken to taken together with the atoms to which they are attached to form a ring having 6 member atoms.12. The composition of claim 1 , wherein the compound of formula I is 4-(tetrahydro-2H-pyran-2-yloxy)phenol.13. The composition of claim 1 , wherein the compound of formula I is present in the composition at a concentration of about 0.5 wt. % to about 10 wt. %.14. The composition of claim 1 , wherein the composition comprises an antioxidant and the antioxidant comprises at least one of ascorbic acid claim 1 , tocopherol claim 1 , butylated hydroxybenzoic acid claim 1 , butylated hydroxytoluene claim 1 , butylated hydroxyanisole claim 1 , uric acid claim 1 , gallic acid claim 1 , sorbic acid claim 1 , glutathione claim 1 , and esters and salts of any thereof.15. The composition of claim 1 , wherein the composition comprises an antioxidant and the antioxidant comprises at least one of ascorbic acid or a salt thereof claim 1 , ascorbyl phosphate or a salt thereof claim 1 , ascorbyl palmitate or a salt thereof claim 1 , tocopherol or a salt thereof claim 1 , tocopheryl acetate and sodium metabisulfite.16. The composition of claim 1 , comprising at least two antioxidants.17. The composition of claim 1 , comprising at least three antioxidants.18. The composition of claim 1 , comprising at least four antioxidants.19. The composition of claim 1 , comprising at least five antioxidants.20. The composition of claim 1 , wherein the composition comprises an antioxidant and the antioxidant is present in an amount of about 0.01 wt. % to about 3.0 wt. %.21. The composition of claim 1 , wherein the composition comprises an antioxidant ...

Fluorescent Chemical Compounds Having High Selectivity for Double Stranded DNA, and Methods for Their Use

Chemical compounds having a high selectivity for double stranded DNA over RNA and single stranded DNA are disclosed. The chemical compounds are stains that become fluorescent upon illumination and interaction with double stranded DNA, but exhibit reduced or no fluorescence in the absence of double stranded DNA. The compounds can be used in a variety of biological applications to qualitatively or quantitatively assay DNA, even in the presence of RNA.

ESTROGEN RECEPTOR MODULATORS AND USES THEREOF

Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors. 2. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , or N-oxide thereof claim 1 , wherein:ring A is 5- or 6-membered monocyclic heteroaryl or 8-, 9- or 10-membered bicyclic heterocycle;ring B is phenyl, naphthyl, 5- or 6-membered monocyclic heteroaryl or 8-, 9- or 10-membered bicyclic heterocycle;ring C is phenyl, or 5- or 6-membered monocyclic heteroaryl;{'sup': 3', '8', '8′', '9', '9', '10', '10', '10', '9', '10', '10', '9', '9, 'sub': 2', '2', '2', '2', '2', '2', '1', '4', '2', '4', '2', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'each Ris independently selected from H, halogen, —NRR, —CN, —OH, —OR, —SR, —S(═O)R, —S(═O)R, —NHS(═O)R, —S(═O)N(R), —C(═O)R, —OC(═O)R, —COR, —C(═O)N(R), C-Calkyl, C-Calkenyl, C-Calkynyl, C-Cfluoroalkyl, C-Cheteroalkyl, C-Cfluoroalkoxy, and C-Calkoxy;'}{'sup': 4', '8', '8′', '9', '9', '10', '10', '10', '9', '10', '10', '9', '10', '9', '9', '9', '9', '9', '10', '9', '10, 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '1', '6', '2', '6', '2', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'each Ris independently selected from H, halogen, —NO, —NRR, —CN, —OH, —OR, —SR, —S(═O)R, —S(═O)R, —NHS(═O)R, —S(═O)N(R), —C(═O)R, —OC(═O)R, —COR, —OCOR, —C(═O)N(R), —OC(═O)N(R), —NRC(═O)N(R), —NRC(═O)R, —NRC(═O)OR, substituted or unsubstituted C-Calkyl, substituted or unsubstituted C-Calkenyl, substituted or unsubstituted C-Calkynyl, substituted or unsubstituted C-Cfluoroalkyl, substituted or unsubstituted C-Cheteroalkyl, substituted or unsubstituted C-Cfluoroalkoxy, substituted or unsubstituted C-Calkoxy, substituted or unsubstituted phenyl and ...

6-alkenyl and 6-phenylalkyl substituted 2-quinolinones and 2-quinoxalinones as poly(adp-ribose) polymerase inhibitors

The present invention provides compounds of formula (I) and compounds of formula (VII-a) as well as pharmaceutical compositions comprising said compounds and their use as PARP inhibitors wherein n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R e , R d and X have defined meanings.

LOW HYGROSCOPIC ARIPIPRAZOLE DRUG SUBSTANCE AND PROCESSES FOR THE PREPARATION THEREOF

The present invention provides low hygroscopic forms of aripiprazole and processes for the preparation thereof which will not convert to a hydrate or lose their original solubility even when a medicinal preparation containing the anhydrous aripiprazole crystals is stored for an extended period. 1. Hydrate A of aripiprazole having an endothermic curve comprising a first endothermic peak at about 71° C. and a second endothermic peak around 60° C. to 120° C. in a thermogravimetric or differential thermal analysis (heating rate 5° C./min).2. The Hydrate A of aripiprazole according to claim 1 , wherein said Hydrate A of aripiprazole has a mean particle size of 50 μm or less.3. The Hydrate A of aripiprazole according to claim 1 , wherein said Hydrate A of aripiprazole has a mean particle size of 20 μm or less.4. The Hydrate A of aripiprazole according to claim 1 , wherein said Hydrate A of aripiprazole has a mean particle size of 36-14 μm.5. Hydrate A of aripiprazole having an endothermic curve which is substantially the same as the thermogravimetric or differential thermal analysis (heating rate 5° C./min) curve shown in .6. The Hydrate A of aripiprazole according to claim 5 , wherein said Hydrate A of aripiprazole has a mean particle size of 50 μm or less.7. The Hydrate A of aripiprazole according to claim 5 , wherein said Hydrate A of aripiprazole has a mean particle size of 20 μm or less.8. The Hydrate A of aripiprazole according to claim 5 , wherein said Hydrate A of aripiprazole has a mean particle size of 36-14 μm.9468. The Hydrate A of aripiprazole according to any one of - and - claims 2 , wherein the mean particle size is measured using a laser diffraction particle size analyzer.10. The Hydrate A of aripiprazole according to claim 9 , wherein the mean particle size is measured using a laser diffraction particle size analyzer by suspending 0.1 g of said Hydrate A of aripiprazole in a 20 mL n-hexane solution of 0.5 g soy lecithin.11. Hydrous aripiprazole having an ...

NMDA Receptor Antagonists for Neuroprotection

Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: 111-. (canceled)13. The method of claim 12 , wherein the administration is for treatment of a host suffering from neuropathic pain.14. The method of claim 12 , wherein the administration is for reducing neuronal injury in a host suffering from a stroke or a traumatic brain injury.1526-. (canceled)28. The method of claim 12 , wherein X is NR.32. The method of claim 12 , wherein W is a bond.33. The method of claim 12 , wherein Y is O.34. The method of claim 12 , wherein Z is NRC(O)NRR.36. The method of claim 12 , wherein the compound is present substantially in the form of a single enantiomer.38. The method of claim 27 , wherein W″ is —CHor CH(OH)—CH—.39. The method of claim 27 , wherein Ar″ is phenyl.40. The method of claim 27 , wherein Z′ is NRC(O)NR.42. The method of claim 27 , wherein Ar′ is substituted with (L′)′ and each L′ is independently C-Calkyl claim 27 , C-Calkoxy claim 27 , C(═O)—(C-C)-alkyl claim 27 , C-Chaloalkyl claim 27 , alkaryl claim 27 , hydroxy claim 27 , —O-alkyl claim 27 , —O-aryl claim 27 , —SH claim 27 , —S-alkyl claim 27 , —S-aryl claim 27 , fluoro claim 27 , chloro claim 27 , bromo claim 27 , iodo claim 27 , nitro claim 27 , or cyano; or two L′ groups may be taken together with Ar′ to form: a dioxolane ring or a cyclobutane ring; andk′=0, 1, 2, 3, 4 or 5.43. The method of claim 42 , wherein an L′ group is in the para position on Ar′.44. The method of claim 43 , wherein L′ in the para position is a halogen.45. The method of claim 43 , wherein L′ in the para position is a C-Calkyl. This application claims priority to U.S. Provisional Application No. 60/ ...

Novel rebamipide complexes and cocrystals

New rebamipide complexes and new rebamipide cocrystals are disclosed, specifically a 1:1 rebamipide nicotinamide complex, a 1:1 rebamipide nicotinamide cocrystal, a 1:1 rebamipide 2,4-dihydroxybenzolc acid complex, and a 1:1 rebamipide 2,4-dihydroxybenzoic acid cocrystal. Pharmaceutical compositions containing a rebamipide complex or cocrystal of the invention and a pharmaceutically acceptable carrier and methods of treatment are also disclosed.

Modulators of atp-binding cassette transporters

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

identification of compounds that disperse tdp-43 inclusions

Herein, methods of modulating inclusion formation and stress granules in cells are described. The methods comprise contacting a cell with an inclusion inhibitor. Methods for screening for modulators of TDP-43 aggregation are also described.

Pharmaceutical compositions having improved storage stability

The present invention relates to a pharmaceutical composition that provides long-term stability of a hydrolytically labile antipsychotic agent

FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS

The present invention relates to sodium channel inhibitors of Formula I: 1. A compound selected from the group consisting of:2-{2-oxo-6-[4-(trifluoromethoxy)phenyl]-3,4-dihydroquinolin-1(2H)-yl}acetamide;2-[6-(2,4-difluorophenyl)-2-oxo-3,4-dihydroquinolin-1 (2H)-yl]acetamide;2-{2-oxo-6-[4-(trifluoromethyl)phenyl]-3,4-dihydroquinolin-1 (2H)-yl}acetamide;2-{6-[4-chloro-3-(trifluoromethyl)phenyl]-2-oxo-3,4-dihydroquinolin-1(2H)-yl}acetamide;tert-butyl 2-(6-(3-fluoro-4-(trifluoromethyl)phenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetate;tert-butyl[6-(2,4-difluorophenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl]acetate;tert-butyl[6-(4-fluorophenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl]acetate;tert-butyl {2-oxo-6-[4-(trifluoromethoxy)phenyl]-3,4-dihydroquinolin-1 (2H)-yl}acetate;tert-butyl {6-[4-chloro-3-(trifluoromethyl)phenyl]-2-oxo-3,4-dihydroquinolin-1(2H)-yl}acetate;ethyl {2-oxo-6-[3-(trifluoromethoxy)phenyl]-3,4-dihydroquinolin-1(2H)-yl}acetate;tert-butyl[6-(3-chlorophenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl]acetate;tert-butyl {2-oxo-6-[4-(trifluoromethyl)phenyl]-3,4-dihydroquinolin-1(2H)-yl}acetate;ethyl[6-(2,4-difluorophenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl]acetate;tert-butyl[6-(4-chlorophenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl]acetate;ethyl[6-(3,4-difluorophenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl]acetate;{2-oxo-6-[3-(trifluoromethoxy)phenyl]-3,4-dihydroquinolin-1(2H)-yl}acetic acid;[6-(4-chlorophenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl]acetic acid;{2-oxo-6-[4-(trifluoromethyl)phenyl]-3,4-dihydroquinolin-1 (2H)-yl}acetic acid;2-(6-(3-fluoro-4-(trifluoromethyl)phenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetic acid;ethyl {2-oxo-6-[4-(trifluoromethoxy)phenyl]-3,4-dihydroquinolin-1(2H)-yl}acetate;[6-(4-fluorophenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl]acetic acid;[6-(3-chloro-4-fluorophenyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl]acetic acid;sodium {2-oxo-6-[4-(trifluoromethyl)phenyl]-3,4-dihydroquinolin-1 (2H)-yl}acetate;[6-(3,4-dichlorophenyl)-2-oxo-3,4-dihydroquinolin-1(2H ...

Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”). 2. A molecule according to claim 1 , wherein Ris selected from the group consisting of H and Cl.3. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , Cl claim 1 , Br claim 1 , CH claim 1 , and CF.4. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , CH claim 1 , CF claim 1 , and OCF.5. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , CH claim 1 , and CF.6. A molecule according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare H.7. A molecule according to claim 1 , wherein Ris Cl.8. A molecule according to claim 1 , wherein Ris Cl.9. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , Cl claim 1 , and CF.10. A molecule according to claim 1 , wherein Ris selected from the group consisting of H and CH.11. A molecule according to claim 1 , wherein Ris selected from the group consisting of cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , azetidinyl claim 1 , morpholinyl claim 1 , oxetanyl claim 1 , pyranyl claim 1 , tetrahydrothiophenyl claim 1 , thietanyl claim 1 , thietanyl-oxide claim 1 , and thietanyl-dioxide claim 1 ,{'sub': 3', '3', '3, 'wherein each cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ...

Pharmaceutical Compositions Having Improved Storage Stability

The present invention relates to a pharmaceutical composition that provides long-term stability of a hydrolytically labile antipsychotic agent 17-. (canceled)8. A method for the preparation of an aqueous pharmaceutical composition comprising a hydrolytically labile antipsychotic agent , wherein the method comprises adding to a composition comprising the antipsychotic agent and an aqueous vehicle (a) a stabilizing amount of a non-ionic water insoluble and/or immiscible ester co-surfactant and (b) a water miscible and/or soluble non-ionic surfactant.9. The method of claim 8 , wherein the composition is in a ready to use form.10. The method of claim 8 , wherein the non-ionic water insoluble and/or immiscible ester co-surfactant is a sorbitan ester of a carboxylic acid claim 8 , wherein the carboxylic acid comprises 4-20 carbon atoms.11. The method of claim 8 , wherein the water miscible and/or soluble non-ionic surfactant is a polyoxyethylene derivative of a sorbitan ester of a carboxylic acid claim 8 , wherein the carboxylic acid comprises 8-14 carbon atoms.12. The method of claim 10 , wherein the sorbitan ester is sorbitan laurate.13. The method of claim 11 , wherein the polyoxyethylene derivative of a sorbitan ester is polysorbate 20.1626-. (canceled)27. A method for treating disorders of the central nervous system claim 8 , comprising administering an effective amount of a composition formed by the method of to an individual in need of such treatment.2829-. (canceled)30. The method of claim 27 , wherein the pharmaceutical composition comprises:(a) a hydrolytically labile antipsychotic agent;(b) a non-ionic water insoluble and/or immiscible ester co-surfactant;(c) a water miscible and/or soluble non-ionic surfactant; and(d) an aqueous vehicle;wherein the pharmaceutical composition comprises less than 50 parts per million of the hydrolysis product of the antipsychotic agent after standing for at least 24 months.31. The method of claim 30 , wherein the pharmaceutical ...

COMPOUNDS FOR TREATMENT OF PD-L1 DISEASES

Compounds are provided that are useful as immunomodulators. The compounds have the Formula (I) 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Ris -A-Z.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Ris —O—X—Y.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Ris -A-Z claim 1 , A is a bond claim 1 , and Z is phenyl claim 1 , optionally substituted with one to three R.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Xis —CH—.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein R claim 1 , Rand Rare H claim 1 , and Ris selected from the group consisting of F claim 1 , Cl claim 1 , CH claim 1 , CFand OCH.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein a ring is formed between one pair of Rand R claim 1 , Rand R claim 1 , Rand R claim 1 , or Rand R.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Ris -A-Z claim 1 , and Z is selected from the group consisting of piperidinyl claim 1 , imidazolyl and pyridinyl.9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein n is 0.10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Ris selected from the group consisting of F claim 1 , Cl claim 1 , CH claim 1 , CFand OCH.11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein the group Ris OCHand Ris F.12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Rand Rare each H.13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Rand Rare combined to form a 4- to 8-membered ring or spirocyclic ring claim 1 , optionally having one or two additional ring vertices selected from O claim 1 , N or S; wherein said ring or spirocyclic ring is substituted with 0 to 4 substituents independently selected from the group ...

PESTICIDALLY ACTIVE SEMI-CARBAZONES AND THIOSEMICARBAZONES DERIVATIVES

Compounds of formula (I), wherein the substituents are as defined in claim 1, and agrochemically acceptable salts and enantiomers thereof, can be used as insecticides. 10. A pesticidal composition claim 1 , which comprises at least one compound of formula I according to claim 1 , where appropriate claim 1 , a tautomer thereof claim 1 , in each case in free form or in agrochemically utilizable salt form claim 1 , as active ingredient and at least one auxiliary.11. A method for controlling pests claim 1 , which comprises applying a compound according to claim 1 , optionally with at least on auxiliary claim 1 , to the pests or their environment with the exception of a method for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.12. A method for the protection of plant propagation material from the attack by pests claim 10 , which comprises treating the propagation material or the site claim 10 , where the propagation material is planted claim 10 , with a composition according to .13. The pesticidal composition of claim 10 , further including a propagation material claim 10 , wherein the composition is coating the propagation material. The present invention relates to compounds of formula (I) below, to processes for preparing them, to pesticidal, in particular insecticidal, acaricidal, molluscicidal and nematicidal compositions comprising them and to methods of using them to combat and control pests such as insect, acarine, mollusc and nematode pests.Heterocyclic compounds with pesticidal activity are known and described, for example, in WO09/102736, WO11/017505, WO12/109125, WO13/116052, WO13/116053 and WO14/011429. There have now been found novel pesticidal active semi-carbazones and thiosemicarbazones with bicyclic rings substituents.The present invention accordingly relates to compounds of formula I,wherein,wherein indicates that the ring is aromatic or non-aromatic;In one embodiment, the present ...

Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”). 2. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , and Cl.3. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , and Cl.4. A molecule according to claim 1 , wherein Ris F or Cl.5. A molecule according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare each independently H.6. A molecule according to claim 1 , wherein Ris selected from the group consisting of Cl and Br.7. A molecule according to claim 1 , wherein Ris selected from the group consisting of Cl and Br.8. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , Cl claim 1 , and CF.9. A molecule according to claim 1 , wherein Ris selected from the group consisting of H and CH.10. A molecule according to claim 1 , wherein Ris selected from the group consisting of CH claim 1 , CHCH claim 1 , CHCHCH claim 1 , CHCHCHCH claim 1 , CHCHCHOCHCH claim 1 , CH claim 1 , CHCH claim 1 , CHCHCH claim 1 , CHCHCHCH claim 1 , CHCHCHCHCH claim 1 , CHCHCHCHCHCH claim 1 , CHCH(CH) claim 1 , CHcyclopropyl claim 1 , CHCHcyclopropyl claim 1 , CHcyclobutyl claim 1 , CHphenyl claim 1 , CHCHphenyl claim 1 , CHC═CH claim 1 , CHC═CH claim 1 , CHCF claim 1 , CHCHF claim 1 , CHCHCF claim 1 , CHCFCF claim 1 , CHCHCHCF claim 1 , CHCHCFCF claim 1 , CHCFCFCF claim 1 , CHCHCHCHF claim 1 , CHCHSCH ...

METHODS FOR THE PREPARATION OF INDACATEROL AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

The invention relates to new and improved processes for the preparation of Indacaterol and pharmaceutically acceptable salts thereof as well as intermediates for the preparation of Indacaterol. The new process avoids the use of the epoxide compound known in the art and the impurities associated therewith and results in a higher yield. 1. (canceled)2. Indacaterol free base in solid form , wherein said Indacaterol free base is in crystalline form.3. Indacaterol free base in solid form , wherein said Indacaterol free base is in amorphous form. The present invention relates to new and improved processes for the preparation of Indacaterol and pharmaceutically acceptable salts thereof as well as intermediates for the preparation of Indacaterol.The compound 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-(1H)-quinolin-2-one, which is known as Indacaterol (INN), and its corresponding salts are beta-selective adrenoceptor agonists with a potent bronchodilating activity. Indacaterol is especially useful for the treatment of asthma and chronic obstructive pulmonary disease (COPD) and is sold commercially as the maleate salt.WO 00/75114 and WO 2004/076422 describe the preparation of Indacaterol for the first time through the process:The condensation between the indanolamine and the quinolone epoxide leads to the desired product but always with the presence of a significant amount of impurities, the most significant being the dimer impurity, which is the consequence of a second addition of the product initially obtained with another quinolone epoxide, as well as the formation of another isomer which is the result of the addition of the indanolamine to the secondary carbon of the epoxide.In addition, the reaction conditions to achieve the opening of the epoxide require high energies (ex. 21 of WO 00/75114) with temperatures of 110° C. or more for several hours, which favours the appearance of impurities.WO 2004/076422 discloses the purification of the reaction ...

2,4-DIOXO-QUINAZOLINE-6-SULFONAMIDE DERIVATIVES AS INHIBITORS OF PARG

The present invention relates to compounds of formula I that function as inhibitors of PARG (Poly ADP-ribose glycohydrolase) enzyme activity wherein R, R, R, R, R, W, X, X, X, X, X, X, X, c are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which PARG activity is implicated. 2. A compound according to claim 1 , wherein bond c is a single bond.3. A compound according to claim 1 , wherein W is selected from —NH—S(O)— claim 1 , —S(O)—NH— claim 1 , —C(O)NH— claim 1 , or —NHC(O)—.5. A compound according to claim 1 , wherein Ris selected from hydrogen claim 1 , fluoro claim 1 , cyano claim 1 , formyl claim 1 , (1-2C)alkyl claim 1 , (1-2C) haloalkyl or (2C)alkynyl.6. A compound according to claim 5 , wherein Ris selected from hydrogen claim 5 , cyano claim 5 , formyl claim 5 , (1-2C)alkyl or (1-2C)haloalkyl.7. A compound according to claim 1 , wherein Xis CR claim 1 , wherein Ris H or fluoro.8. A compound according to claim 7 , wherein Xis C—H.9. A compound according to claim 1 , wherein Xis CR claim 1 , wherein Ris H or fluoro.10. A compound according to claim 1 , wherein Xis selected form CRor N; wherein Ris H or halo.11. A compound according to claim 10 , wherein Xis C—H claim 10 , C—F or C—C(O)NH.12. A compound according to claim 1 , wherein R claim 1 , R claim 1 , Rand Rare H.13. A compound according to claim 1 , wherein Xis selected from C(═O) claim 1 , C(═NH) claim 1 , C(═S) claim 1 , CHRor N—Rwhen bond a is a single bond claim 1 , or CRor N when bond a is a double bond;wherein{'sub': '5c', 'Ris selected from H, fluoro, (1-2C)alkyl, cyano or (2C)alkynyl;'}{'sub': 5N', '3, 'Ris selected from H, (1-2C)alkyl or CF.'}14. A compound according to claim 1 , wherein Xis C(═O) and bond a is a single bond.15. A compound according to claim 1 , ...

ORGANIC REACTIONS CARRIED OUT IN AQUEOUS SOLUTION IN THE PRESENCE OF A HYDROXYALKYL(ALKYL)CELLULOSE OR AN ALKYLCELLULOSE

The present invention relates to a method of carrying out an organic reaction in aqueous solution in the presence of a hydroxyalkyl(alkyl)cellulose or an alkylcellulose. 1. A method of carrying out an organic reaction in a solvent containing at least 90% by weight , based on the total weight of the solvent , of water , which method comprises reacting the reagents in said solvent in the presence of a cellulose derivative as a surfactant which is selected from the group consisting of cellulose modified with one or more alkylene oxides or other hydroxyalkyl precursors , and alkylcellulose;where the organic reaction is not a polymerization or oligomerization reaction of olefinically unsaturated compounds; and [ a transition metal catalyzed C—C coupling reaction:', 'a transition metal catalyzed reaction involving C—N bond formation which is an Au-catalyzed cyclodehydratization of α,β-amino alcohols containing a C—C triple bond:', 'a transition metal catalyzed reaction involving C—O bond formation:', 'a transition metal catalyzed reaction involving C—S bond formation:', 'a transition metal catalyzed reaction involving C—B bond formation: or', 'a transition metal catalyzed reaction involving C-halogen bond formation; or, 'a transition metal catalyzed reaction in which a transition metal catalyst is used; where the transition metal catalyzed reaction is'}, 'a C—C coupling reaction not requiring transition metal catalysis which is selected from the group consisting of reactions of carbonyl or nitrile compounds and pericyclic reactions;, 'where the organic reaction is'}a nucleophilic substitution reaction;a reduction or an oxidation reaction; oran ester formation reaction or an ester hydrolysis reaction.2. The method as claimed in claim 1 , where the cellulose derivative has a viscosity of from 1 to 150000 mPa·s claim 1 , determined as a 2% by weight aqueous solution claim 1 , relative to the weight of water.3. The method as claimed in claim 1 , where in the cellulose ...

Improved process for the preparation of aripiprazole lauroxil

The present invention relates to an improved process for the preparation of Aripiprazole Lauroxil of Formula (I).

Substituted 1-cycloalkyl-2-oxotetrahydroquinolin-6-ylsulfonamides or salts thereof and use thereof to increase stress tolerance in plants

Substituted 1-cycloalkyl-2-oxotetrahydroquinolin-6-ylsulfonamides or salts thereof as active ingredients to counter abiotic plant stress 2. Substituted 1-cycloalkyl-2-oxotetrahydroquinolin-6-ylsulfonamide of the formula (I) and/or a salt thereof as claimed in claim 1 , in which{'sup': '1', 'sub': 1', '6', '3', '8', '3', '8', '4', '8', '4', '8', '1', '8', '2', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '2', '6', '2', '6', '2', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '6', '1', '6', '2', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '2', '6', '2', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '4', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '6', '2', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '6', '1', '6', '2', '6', '1', '6', '2', '6', '1', '6', '2', '6', '1', '6', '3', '6', '1', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '2', '6', '1', '6', '2', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '6', '1', '6', '2', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '6', '1', '6', '1', '6', '2', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '2', '6', '1', '6', '2', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1 ...

Multi-API Loading Prodrugs

The present invention accomplishes this by having multiple molecules of parent drugs attached to carrier moieties and by extending the period during which the parent drug is released and absorbed after administration to the patient and providing a longer duration of action per dose than the parent drug itself. Prodrug conjugates are suitable for sustained delivery of heteroaryl, lactam-amide-, imide-, sulfonamide-, carbamate-, urea-, benzamide-, acylaniline-, cyclic amide- and tertiary amine-containing parent drugs that are substituted at the amide nitrogen or oxygen atom with labile aldehyde-linked prodrug moieties. The carrier groups of the prodrugs can be hydrophobic to reduce the polarity and solubility of the parent drug under physiological conditions. 115-. (canceled)2027-. (canceled)29. (canceled)301. A method for sustained delivery of a parent drug to a patient comprising administering a prodrug compound of claim , wherein upon administration to the patient , release of the parent drug from the prodrug is sustained.3133-. (canceled)34. A method of synthesizing a compound of formula I , IA or IB comprising the steps of reacting a dicarboxylic acid containing compound with thionyl chloride followed by reacting with formaldehyde or trioxane to yield chloromethyl ester which is reacted with a biologically active compound to give said compound of formula I , IA , IB.3580-. (canceled) This application is a continuation of U.S. application Ser. No. 13/335,405, filed Dec. 22, 2011, which claims the benefit of U.S. Provisional Application No. 61/427,026, filed on Dec. 23, 2010. The entire teachings of the above applications are incorporated herein by reference.The present invention relates to prodrugs that can be linked to multiple drug molecules.Drug delivery systems are often critical for the safe and effective administration of a biologically active agent. Perhaps the importance of these systems is best realized when patient compliance and consistent dosing are ...

Process for Synthesizing Oxidized Lactam Compounds

The invention provides a method for the synthesis of dehydrogenated lactam drugs of Formula I: 7. The method according to claim 2 , wherein B is selected from a direct bond claim 2 , a straight chain C-Calkyl claim 2 , C-Calkenyl claim 2 , C-Calkynyl claim 2 , C-Calkoxy claim 2 , alkoxyC-Calkoxy claim 2 , C-Calkylamino claim 2 , alkoxyC-Calkylamino claim 2 , C-Calkylcarbonylamino claim 2 , C-Calkylaminocarbonyl claim 2 , aryloxyC-Calkoxy claim 2 , aryloxyC-Calkylamino claim 2 , aryloxyC-Calkylamino carbonyl claim 2 , C-C-alkylaminoalkylaminocarbonyl claim 2 , C-Calkyl(N-alkyl)aminoalkyl-aminocarbonyl claim 2 , alkylaminoalkylamino claim 2 , alkylcarbonylaminoalkylamino claim 2 , alkyl(N-alkyl)aminoalkylamino claim 2 , (N-alkyl)alkylcarbonylaminoalkylamino claim 2 , alkylaminoalkyl claim 2 , alkylaminoalkylaminoalkyl claim 2 , alkylpiperazinoalkyl claim 2 , piperazinoalkyl claim 2 , alkylpiperazino claim 2 , alkenylaryloxyC1-C10alkoxy claim 2 , alkenylarylaminoC-Calkoxy claim 2 , alkenylaryllalkylaminoC-Calkoxy claim 2 , alkenylaryloxyC-Calkylamino claim 2 , alkenylaryloxyC-Calkylaminocarbonyl claim 2 , piperazinoalkylaryl claim 2 , heteroarylC-Calkyl claim 2 , heteroarylC-Calkenyl claim 2 , heteroarylC-Calkynyl claim 2 , heteroarylC-Calkylamino claim 2 , heteroarylC-Calkoxy claim 2 , heteroaryloxyC-Calkyl claim 2 , heteroaryloxyC-Calkenyl claim 2 , heteroaryloxyC-Calkynyl claim 2 , heteroaryloxyC-Calkylamino and heteroaryloxyC-Calkoxy.8. A method according to claim 2 , wherein Ris selected from H claim 2 , —C(R)(R)—OR claim 2 , —C(R)(R)—OC(O)OR claim 2 , —C(R)(R)—OC(O)R claim 2 , —C(R)(R)—OC(O)NRR claim 2 , —(C(R)(R))—OPOMY claim 2 , —(C(R)(R))—OP(O)(OR)(OR) claim 2 , —[C(R)(R)O]—R claim 2 , —[C(R)(R)O]—C(O)OR claim 2 , —[C(R)(R)O]—C(O)R claim 2 , —[C(R)(R)O]—C(O)NRR claim 2 , —[C(R)(R)O]-OPOMY claim 2 , —[C(R)(R)O]—P(O)(OR)M and —[C(R)(R)O]—P(O)(OR)(OR);{'sub': J', 'K, 'wherein each Rand Ris independently selected from hydrogen, halogen, aliphatic, substituted ...

METHODS AND COMPOSITIONS FOR INHIBITION OF BROMODOMAIN-CONTAINING PROTEINS

The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders. 3. A compound of wherein Ris selected from substituted or unsubstituted aryl claim 2 , or substituted or unsubstituted heteroaryl.4. A compound of wherein Ris NC(O)OR.5. A compound of wherein Ris hydrogen.6. A compound of wherein Ris selected from substituted or unsubstituted aryl claim 2 , or substituted or unsubstituted heteroaryl.7. A compound of wherein Rand Rare independently selected from substituted or unsubstituted aryl claim 2 , or substituted or unsubstituted heteroaryl.8. A compound of wherein Lis —(C—RR)— wherein Rand Rare independently selected from hydrogen and methyl and n is 1 or 2.9. A compound of wherein Lis selected from alkyl claim 2 , CONRR claim 2 , and SONRR.10. A compound of wherein Ris hydrogen.11. A compound of wherein Ris selected from substituted or unsubstituted aryl claim 3 , or substituted or unsubstituted heteroaryl.12. A compound of wherein Rand Rare independently selected from hydrogen claim 3 , substituted or unsubstituted aryl claim 3 , and substituted or unsubstituted heteroaryl.13. A compound of wherein Lis —(C—RR)— wherein Rand Rare independently selected from hydrogen and methyl and nA is 1 or 2.14. A compound of wherein Lis selected from the group consisting of alkyl claim 3 , —CONRR claim 3 , and —SONRR.15. A compound of wherein Ris selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; Ris NC(O)OR; Ris hydrogen; Ris selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; Rand Ris selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; Lis —(C—RR)— wherein Rand Rare independently selected from ...

PROCESS FOR THE PREPARATION OF ANHYDROUS ARIPIPRAZOLE CRYSTAL FORM II

The present invention relates to a process for preparation of aripiprazole crystal form II by recrystallizing aripiprazole in a mixture of acetone and 1-methoxy-2-propanol or a single solvent of 1-methoxy-2-propanol. The simple process according to the present invention can produce aripiprazole crystal form II with high purity and high yield in a mass scale. 1. A process for preparation of anhydrous aripiprazole crystal form II , which comprises the following steps:a) introducing aripiprazole crystals into a mixed solvent of acetone and 1-methoxy-2-propanol or a single solvent of 1-methoxy-2-propanol;b) dissolving the crystal with heating and stirring;c) seeding a crystal of aripiprazole crystal form II; andd) isolating the desired aripiprazole crystal form II from the solution.2. The process according to claim 1 , wherein the resulting anhydrous aripiprazole crystal form II shows the diffraction angles of 2θ=16.5 claim 1 , 18.7 claim 1 , 21.9 claim 1 , 22.4 and 23.5±0.2 in X-ray powder diffraction analysis.3. The process according to claim 1 , wherein in step a) aripiprazole crystal form III is used.4. The process according to claim 1 , wherein aripiprazole crystal is dissolved in the mixture of acetone and 1-methoxy-2-propanol with heating at 45° C. to 60° C.5. The process according to or claim 1 , wherein after dissolving aripiprazole crystal in the mixture of acetone and 1-methoxy-2-propanol claim 1 , aripiprazole crystal form II is seeded thereto at 35° C. to 65° C.6. The process according to claim 1 , wherein aripiprazole crystal is dissolved in the single solvent of 1-methoxy-2-propanol with heating at 70° C. to 90° C.7. The process according to or claim 1 , wherein after dissolving aripiprazole crystal in the single solvent of 1-methoxy-2-propanol claim 1 , aripiprazole crystal form II is seeded thereto at 35° C. to 75° C.8. The process according to claim 1 , which further comprises the washing and drying steps. The present invention relates to a novel ...

Modulators of atp-binding cassette transporters

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

SHIP1 MODULATORS AND METHODS RELATED THERETO

Compounds of formula (II): wherein A, R, R, Rand Rare described herein, or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof, are described herein, as well as other compounds. These compounds have activity as SHIP1 modulators, and thus may be useful in treating a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of the invention are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof. 3. The compound of wherein:{'sup': 1', '8', '9, 'Ris —R—OR;'}{'sup': 2', '8', '9, 'Ris —R—OR;'}{'sup': 3', '8', '9', '11', '8', '9', '12', '8', '9', '9a', '8', '9', '9a', '8', '9', '9a, 'sub': 2', '2', '2, 'Ris —R—N(R)C(O)R, —R—N(R)—R, —R—N(R)C(═NCN)N(R), —R—N(R)C(O)N(R)or —R—N(R)C(S)N(R);'}{'sup': 4a', '4b, 'Rand Rare each independently hydrogen, alkyl, alkenyl or alkynyl;'}{'sup': 4a', '4b', '7, 'or Ris hydrogen, alkyl, alkenyl or alkynyl and Ris a direct bond to the carbon to which Ris attached;'}{'sup': 4a', '4b, 'or Rand Rtogether form alkylidene or haloalkylidene;'}{'sup': 5', '5, 'Ris alkyl or Ris a direct bond to the carbon at C14;'}{'sup': 6', '8', '9', '8', '9, 'sub': '2', 'Ris hydrogen, —R—ORor —R—N(R);'}{'sup': 7', '8', '9', '8', '9', '7', '4b', '7, 'sub': '2', 'Ris hydrogen, —R—OR, —R—N(R), or a direct bond to C15, provided that when Ris a direct bond to C15, Ris not a direct bond to the carbon to which Ris attached;'}{'sup': '8', 'each Ris independently a direct bond or a straight or branched alkylene chain;'}{'sup': '9', 'each Ris hydrogen, alkyl, optionally substituted aryl and optionally substituted aralkyl;'}{'sup': '9a', 'each Ris hydrogen, alkyl, optionally substituted aryl, optionally substituted aralkyl;'}optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ...

PROCESS AND INTERMEDIATES FOR THE PREPARATION OF BENZO[B]THIOPHENE COMPOUNDS

A process for preparing compounds of formula (I), or a salt or solvate thereof, including Brexpiprazole, which process comprises cyclization of a compound of formula (II) or (III), or a salt or solvate thereof. The invention also refers to intermediates of said process. 5. Process according to claim 1 , wherein Rand Rare —CHO.7. Process according to claim 1 , wherein the cyclization of a compound of formula (II) or (III) claim 1 , or a salt or solvate thereof claim 1 , is carried out in the presence of an acid.9. Process according to claim 1 , wherein the compound of formula (I) is selected from (l-benzothiophen-4-yl)piperazine and Brexpiprazole claim 1 , or a salt or solvate thereof.1314-. (canceled) The invention relates to a process for preparing benzo[b]thiophene compounds that can be used to obtain therapeutically useful compounds, such as Brexpiprazole.Brexpiprazole, discovered by Otsuka, is a dopamine D2 receptor partial agonist. It has been recently approved by the FDA for the treatment of schizophrenia and as an adjunctive therapy for the treatment of major depression.The chemical name of Brexpiprazole is (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one), and is represented by the following formula:The synthesis of this compound was first disclosed in EP 1869025 by a process comprising palladium-catalyzed cross-coupling of non-commercial 4-bromo-benzo[b]thiophene and piperazine, followed by substitution of the piperazine with the butoxy-quinolinone derivative (Reference Example 30 and Example 1).In addition to being expensive, the Pd-catalyzed cross-coupling reaction is not clean and gives rise to a product with reduced purity, as acknowledged by the applicant in the subsequent patent application WO 2013/015456.WO 2013/015456 discloses a similar method for preparing Brexpiprazole, but starting from 4-chloro-benzo[b]thiophene and using smaller amounts of Pd and phosphines to cheapen the process (Examples 1-4). However, obtaining 4- ...

2,3-disubstituted 1-acyl-4-amino-1,2,3,4-tetrahydroquinoline derivatives and their use as bromodomain inhibitors

The present invention relates to novel compounds, pharmaceutical compositions containing such compounds and to their use in therapy.

2- (TERT - BUTOXY) -2- (7 -METHYLQUINOLIN- 6 - YL) ACETIC ACID DERIVATIVES FOR TREATING AIDS

The invention provides compounds and salts thereof as d herein. The invention also provides pharmaceutical compositions comprising a compound disclosed herein, processes for preparing compounds disclosed herein, intermediates useful for preparing compounds disclosed herein and therapeutic methods for treating an HIV infection, treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds disclosed herein. 5. A pharmaceutical composition comprising a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.6. A method of treating an HIV infection in a patient in need thereof comprising administering a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to the patient.7. A method of treating an HIV infection in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , in combination with a therapeutically effective amount of one or more additional therapeutic agents selected from the group consisting of HIV protease inhibiting compounds claim 1 , HIV non-nucleoside inhibitors of reverse transcriptase claim 1 , HIV nucleoside inhibitors of reverse transcriptase claim 1 , HIV nucleotide inhibitors of reverse transcriptase claim 1 , HIV integrase inhibitors claim 1 , gp41 inhibitors claim 1 , CXCR4 inhibitors claim 1 , gp120 inhibitors claim 1 , CCR5 inhibitors claim 1 , capsid polymerization inhibitors claim 1 , and other drugs for treating HIV.811-. (canceled)12. A pharmaceutical composition comprising a compound as described in claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , and a pharmaceutically acceptable carrier.13. A method of treating an HIV infection in a patient in need thereof comprising administering a compound as ...

Antibacterial compounds and uses thereof

The present invention relates to compounds of formula (I) including any stereochemically isomeric form thereof, or pharmaceutically acceptable salts thereof, for the treatment of tuberculosis.

SYNTHETIC COMPOUNDS FOR VEGETATIVE ABA RESPONSES

The present invention provides agonist compounds that active ABA receptors, and agricultural formulations comprising the agonist compounds. The agricultural formulations are useful for inducing ABA responses in plant vegetative tissues, reducing abiotic stress in plants, and inhibiting germination of plant seeds. The compounds are also useful for inducing expression of ABA-responsive genes in cells that express endogenous or heterologous ABA receptors. 4. The formulation of claim 2 , wherein{'sup': '1', 'sub': '1-6', 'Ris Calkyl, and'}{'sup': 2', '2a, 'Ris selected from the group consisting of aryl and heteroaryl, each optionally substituted with from 1-4 Rgroups.'}5. The formulation of claim 4 , wherein each Ris independently selected from the group consisting of H claim 4 , halogen and Calkyl.6. The formulation of claim 4 , wherein Ris selected from the group consisting of phenyl claim 4 , naphthyl claim 4 , thiophene claim 4 , furan claim 4 , pyrrole claim 4 , and pyridyl.7. The formulation of claim 4 , wherein{'sup': '1', 'Ris selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl, tert-butyl, pentyl, isopentyl, neo-pentyl and hexyl;'}{'sup': 2', '2a, 'Ris selected from the group consisting of phenyl and thiophene, each optionally substituted with 1 Rgroup;'}{'sup': '2a', 'each Ris independently selected from the group consisting of H, F, Cl, methyl, and ethyl; and'}L is selected from the group consisting of a bond and methylene.1018. The formulation of claim 1 , wherein the compound is one of the compounds shown in or .12. The formulation of claim 1 , further comprising at least one of a fungicide claim 1 , an herbicide claim 1 , a pesticide claim 1 , a nematicide claim 1 , an insecticide claim 1 , a plant activator claim 1 , a synergist claim 1 , an herbicide safener claim 1 , a plant growth regulator claim 1 , an insect repellant claim 1 , an acaricide claim 1 , a molluscicide claim 1 , or a fertilizer.13. The ...

INHIBITORS OF LATE SV40 FACTOR (LSF) AS CANCER CHEMOTHERAPEUTICS

The present invention is directed to methods, compositions and kits for treatment of cancer, e.g. heptacellular carcinoma. In some embodiments, the present invention discloses the use of a small-molecule compound of formula (I)-(XXVI) and (III′) as disclosed herein to inhibit transcription factor Late SV40 Factor (LSF) for treatment of cancer, e.g., HCC. 2. The compound of claim 1 , wherein R′ is a phenyl substituted with at least one C-Calkoxyl and at least one di(C-Calkyl)amino.4. The compound of claim 3 , wherein Rand Rare independently selected C-Calkyl.8. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient or carrier.9. A method of inhibiting LSF in a subject claim 1 , the method comprising administering an effective amount of a compound of to a subject in need thereof.10. The method of claim 9 , wherein the subject suffers from or is at risk of cancer.11. The method of claim 10 , wherein the cancer is hepatocellular carcinoma (HCC).12. The method of claim 10 , wherein the cancer is selected from the group consisting of breast cancer claim 10 , color cancer claim 10 , ovarian cancer claim 10 , lung cancer claim 10 , kidney cancer claim 10 , cancers of the hematopoietic system claim 10 , cancers of the endometrium claim 10 , cervical cancer claim 10 , cancers of the upper digestive tract claim 10 , stomach cancer claim 10 , liver cancers and cancers of the small intestine.13. The method of claim 9 , wherein the subject suffers from or is at risk of HIV or is in need of lower inflammatory responses.15. A method for treating cancer in a subject claim 1 , the method comprising administering an effective amount of a compound of to a subject in need thereof.16. The method of claim 15 , wherein the cancer is hepatocellular carcinoma (HCC).17. The method of claim 15 , wherein the cancer is selected from the group consisting of breast cancer claim 15 , color cancer claim 15 , ovarian cancer claim 15 , lung cancer claim 15 , ...

2-OXO-3,4-DIHYDROQUINOLINE COMPOUNDS AS PLANT GROWTH REGULATORS

The present invention relates to novel sulfonamide derivatives of formula (I), to processes and intermediates for preparing them, to plant growth regulator compositions comprising them and to methods of using them for controlling the growth of plants, improving plant tolerance to abiotic stress (including environmental and chemical stresses), inhibiting seed germination and/or safening a plant against phytotoxic effects of chemicals. 2. A compound according to claim 1 , wherein R1 is selected from the group consisting of C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-Calkenyl and C-Ccyclopropyl-C-C-alkyl.3. A compound according to claim 2 , wherein R1 is ethyl or propyl.4. A compound according to claim 1 , wherein L is a bond.5. A compound according to claim 1 , wherein A is selected from the group consisting of C-Calkyl claim 1 , phenyl and 3-6 membered heteroaryl claim 1 , each optionally substituted with one to three Ry.6. A compound according to claim 5 , wherein A is phenyl optionally substituted with one to three substituents independently selected from the group consisting of halogen claim 5 , C-Chaloalkyl claim 5 , C-Calkyl and C-Chaloalkoxy.7. A compound according to claim 1 , wherein R2 is selected from the group consisting of hydrogen and C-Calkyl.8. A compound according to claim 1 , wherein R3 is selected from the group consisting of hydrogen claim 1 , halogen and C-Calkyl.9. A compound according to claim 1 , wherein R2 claim 1 , R3 claim 1 , R4 claim 1 , R5 claim 1 , R6 claim 1 , R7 and R8 are hydrogen.10. A compound according to claim 1 , and an agriculturally acceptable formulation adjuvant claim 1 , combined and thereby forming a composition.11. A compound as defined in claim 1 , and a further active ingredient.12. A method for at least one of improving the tolerance of a plant to abiotic stress claim 1 , regulating the growth of a plant claim 1 , or improving the growth of a plant claim 1 , wherein the method comprises applying to the plant claim 1 , ...

SELECTIVE BETA-GLUCURONIDASE INHIBITORS AS A TREATMENT FOR SIDE EFFECTS OF CAMPTOTHECIN ANTINEOPLASTIC AGENTS

Compounds, compositions and methods are provided that comprise selective β-glucuronidase inhibitors for both aerobic and anaerobic bacteria, especially enteric bacteria normally associated with the gastrointestinal tract. The compounds, compositions and methods can be for inhibiting bacterial β-glucuronidase and for improving efficacy of camptothecin-derived antineoplastic agents or glucuronidase-substrate agents or compounds by attenuating the side effects caused by reactivation by bacterial β-glucuronidases of glucuronidated metabolites of camptothecin-derived antineoplasatic agents or glucuronidase-substrate agents or compounds. 121-. (canceled)22. A method for attenuating side effects in a subject being administered a camptothecin-derived antineoplastic agent , the method comprising administering prior to , concurrently with or after administration of a camptothecin-derived antineoplastic agent a therapeutically effective amount of at least one selective enteric bacterial β-glucuronidase inhibitor.23. The method of claim 22 , wherein said camptothecin-derived antineoplastic agent inhibits topoisomerase I.24. The method of claim 22 , wherein said camptothecin-derived antineoplastic agent is selected from the group consisting of camptothecin claim 22 , diflomotecan claim 22 , exatecan claim 22 , gimatecan claim 22 , irinotecan claim 22 , karenitecin claim 22 , lurtotecan claim 22 , rubitecan claim 22 , silatecan and topotecan.25. The method of claim 24 , wherein said camptothecin-derived antineoplastic agent is camptothecin or irinotecan.26. The method of claim 22 , wherein said selective enteric bacterial β-glucuronidase inhibitor is administered prior to said administration of a camptothecin-derived antineoplastic agent.27. The method of claim 22 , wherein said selective enteric bacterial β-glucuronidase inhibitor is administered concurrently with said administration of a camptothecin-derived antineoplastic agent.28. The method of claim 22 , wherein said ...

ENDOPARASITE CONTROL AGENT

The present invention is intended to provide a novel parasiticide, antiprotozoal or other endoparasite control agents which are effective for controlling animal endoparasites that have been impossible to control by conventional ones. Provided is an endoparasite control agent comprising, as an active ingredient, a carboxamide derivative represented by the general formula (I): 111-. (canceled)13. The method according to claim 12 , wherein the endoparasite control agent is orally or parenterally administered to a non-human mammal.14. The method according to claim 13 , wherein the non-human mammal is a domestic animal.15. The method according to claim 12 , wherein the mammal is a human.16. The method according to claim 12 , wherein the mammal is a non-human mammal. The present invention relates an endoparasite control agent comprising a carboxamide derivative or a salt thereof as an active ingredient, and a method for controlling endoparasites, comprising orally or parenterally administering the endoparasite control agent.Certain kinds of carboxamide derivatives have been known to have microbicidal activity (see Patent Literature 1 to 12). However, the literature does not describe that these compounds are effective for the disinfection or control of endoparasites in animals such as mammals and birds. It is also known that certain kinds of carboxamide derivatives are effective against nematodes that may damage agricultural products (see Patent Literature 4 or 5), but there is no specific disclosure as to whether these compounds are effective against endoparasites in animals. Furthermore, there is a report that compounds that inhibit succinate-ubiquinone reductase (mitochondrial complex II), which is one of the respiratory enzymes of endoparasites, can serve as an endoparasite control agent (see Non Patent Literature 1).In addition, Patent Literature 13 discloses certain kinds of carboxamide derivatives which are effective against endoparasites. However, there is no ...

Compounds for use in screening methods for spinal muscular atrophy

Disclosed herein are compositions and methods for treatment of spinal muscular atrophy (SMA). In certain embodiments, compounds are provided that increase full-length survival of motor neuron (SMN) protein production by an SMN2 gene.

COMPOUNDS FOR INHIBITION OF ALPHA 4 BETA 7 INTEGRIN

The present disclosure provides a compound of Formula (I): 15. The compound of claim 1 , wherein Zis N claim 1 , and each of Z claim 1 , Z claim 1 , and Zis CH.16. The compound of or claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Rand Ris independently selected from H claim 1 , and halo.17. The compound of any one of claim 1 , claim 1 , and or a pharmaceutically acceptable salt thereof claim 1 , wherein each Rand Ris H.18. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Rand Ris independently selected from H claim 1 , halo claim 1 , Calkyl claim 1 , Calkoxyl claim 1 , Chaloalkyl claim 1 , and Chaloalkoxyl.19. The compound of any one of to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Rand Ris independently selected from F claim 1 , and —CH.20. The compound of any one of to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris F claim 1 , and Ris —CH.21. The compound of any one of - claim 1 , claim 1 , and - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris 6-membered heterocyclyl optionally substituted with one to three R; and wherein each Ris independently selected from halo claim 1 , Calkyl claim 1 , and Chaloalkyl.22. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from —CH claim 1 , —CHF claim 1 , and —CF.23. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CF.27. The compound of any one of - claim 1 , claim 1 , and - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —NRR; and wherein Rand Ris independently selected from H claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , and Ccycloalkyl.29. The compound of any one of claim 1 , and claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis N claim 1 , and Xis O.30. The ...

INHIBITORS OF LATE SV40 FACTOR (LSF) AS CANCER CHEMOTHERAPEUTICS

The present invention is directed to methods, compositions and kits for treatment of cancer, e.g. heptacellular carcinoma. In some embodiments, the present invention discloses the use of a small-molecule compound of formula (I)-(XXVI) and (III′) as disclosed herein to inhibit transcription factor Late SV40 Factor (LSF) for treatment of cancer, e.g., HCC. 2. The compound of claim 1 , wherein R is a phenyl substituted with at least one C-Calkoxyl and at least one di(C-Calkyl)amino claim 1 , halogen or C-Calkenyl.6. The compound of claim 1 , wherein the compound is FQI-34.7. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient or carrier.8. A method of inhibiting LSF in a subject claim 1 , the method comprising administering an effective amount of a compound of to a subject in need thereof.9. The method of claim 8 , wherein the subject suffers from or is at risk of cancer.10. The method of claim 9 , wherein the cancer is hepatocellular carcinoma (HCC).11. The method of claim 9 , wherein the cancer is selected from the group consisting of breast cancer claim 9 , color cancer claim 9 , ovarian cancer claim 9 , lung cancer claim 9 , kidney cancer claim 9 , cancers of the hematopoietic system claim 9 , cancers of the endometrium claim 9 , cervical cancer claim 9 , cancers of the upper digestive tract claim 9 , stomach cancer claim 9 , liver cancers and cancers of the small intestine.12. The method of claim 8 , wherein the subject suffers from or is at risk of HIV or is in need of lower inflammatory responses.14. The method of claim 8 , wherein the compound is FQI-34.15. A method for treating cancer in a subject claim 1 , the method comprising administering an effective amount of a compound of to a subject in need thereof.16. The method of claim 15 , wherein the cancer is hepatocellular carcinoma (HCC).17. The method of claim 15 , wherein the cancer is selected from the group consisting of breast cancer claim 15 , color cancer ...

NOVEL POLYMORPHIC CRYSTAL FORMS OF 5-(2--1-(R)-HYDROXYETHYL)-8-HYDROXYQUINOLIN-2(1H)-ONE, HEMINAPADISYTLATE AS AGONIST OF THE BETA2 ADRENERGIC RECEPTOR

The present invention is directed to novel polymorphic crystal forms of a 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one, heminapadisylate. The invention is also directed to pharmaceutical compositions comprising said polymorphic crystal forms, methods of using them to treat respiratory diseases associated with β2 adrenergic receptor activity and a process for preparing such polymorphic crystal forms. 1. A crystalline polymorph of 5-(2-{[6-(2 ,2-difluoro-2-phenylethoxy)hexyl]amino}-1(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one heminapadisylate , which is chosen from (i) a hydrate polymorph , or (ii) a type β polymorph prepared by drying said hydrate polymorph , wherein:the hydrate polymorph has:a) an X-Ray Powder Diffraction (XRPD) pattern with peaks at 13.3, 16.1 and 19.2 degrees 2θ (±0.1 degrees 2θ); and/orb) a Differential Scanning Calorimetry (DSC) pattern with a first endotherm in the range 75-120° C. (±5° C.) and a second endotherm with an onset at 190° C. (±10° C.),the type β polymorph has:a) an X-Ray Powder Diffraction (XRPD) pattern with a peak at 19.1 degrees 2θ (±0.1 degrees 2θ); and/orb) a Differential Scanning Calorimetry (DSC) pattern with an endotherm with an onset at 190° C. (±1° C.).2. The crystalline polymorph according to claim 1 , wherein the hydrate polymorph is prepared by:a) adding a solution of naphthalene-1,5-disulfonic acid tetrahydrate in methanol/acetic acid (1:1) to a solution of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one in methanol/acetic acid (1:1) to form a reaction mixture,b) stirring the reaction mixture at reflux for 30 minutes and allowing the reaction mixture to cool down to 20-25° C., then stirring at 20-25° C. for 20 hours,c) isolating by filtrating and washing with methanol, and drying at 50° C. to obtain the hydrate polymorph.3. The crystalline polymorph according to claim 1 , wherein the crystalline polymorph is the ...

Pharmaceutical Compositions Having Improved Storage Stability

The present invention relates to a pharmaceutical composition that provides long-term stability of a hydrolytically labile antipsychotic agent 115-. (canceled)17. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises less than 30 parts per million of the hydrolysis product of Compound 1 after standing for at least 24 months.18. (canceled)19. The pharmaceutical composition of claim 16 , wherein the water miscible and/or soluble non-ionic surfactant is a polyoxyethylene derivative of a sorbitan ester of a carboxylic acid claim 16 , wherein the carboxylic acid comprises 8-14 carbon atoms.20. The pharmaceutical composition of claim 16 , wherein the sorbitan ester is sorbitan laurate.21. The pharmaceutical composition of claim 19 , wherein the polyoxyethylene derivative of a sorbitan ester is polysorbate 20.22. (canceled)2427-. (canceled)29. (canceled)30. A method of treating schizophrenia in a subject in need thereof comprising administering to the subject the composition of .31. A method of treating schizophrenia in a subject in need thereof comprising administering to the subject the composition of .32. A method of treating bipolar disorder in a subject in need thereof comprising administering to the subject the composition of .33. A method of treating anxiety in a subject in need thereof comprising administering to the subject the composition of .34. A method of treating depression in a subject in need thereof comprising administering to the subject the composition of .35. A method of treating autism-related irritability in a subject in need thereof comprising administering to the subject the composition of .36. A method of treating acute mania in a subject in need thereof comprising administering to the subject the composition of . This application claims priority to U.S. Provisional Application No. 61/702,881, filed Sep. 19, 2012 and to U.S. Provisional Application No. 61/780,862, filed Mar. 13, 2013. The entire contents of ...

New Aryl-Quinoline Derivatives

The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and n are as described herein, compositions including the compounds and methods of using the compounds. The present compounds are useful as fatty-acid binding protein (FABP) 4 and/or 5 inhibitors and may be used for the treatment or prophylaxis of lipodystrophy, type 2 diabetes, dyslipidemia, atherosclerosis, liver diseases involving inflammation, steatosis and/or fibrosis, such as non-alcoholic fatty liver disease, in particular non-alcoholic steatohepatitis, metabolic syndrome, obesity, chronic inflammatory and autoimmune inflammatory diseases.

ARIPIPRAZOLE TYPE I MICROCRYSTAL, ARIPIPRAZOLE SOLID PREPARATIONS, AND PREPARATION METHOD

A method for preparing an aripiprazole type I microcrystal, including the following steps: dissolving aripiprazole in an acidifier, acquiring a medicament-having acid solution; adding an alkalizer while stirring, then adding water or aqueous ethanol 10 to 60 wt % while stirring, and separating by precipitation the aripiprazole type I microcrystal. Furthermore, a method for preparing a solid preparation having the aripiprazole type I microcrystal, an aripiprazole microcrystal having an average particle size of less than 24 μm, and a solid preparation having the microcrystal. The method for preparing the aripiprazole type I microcrystal allows reduced pollution and loss, great safety, easy and convenient, reduced use of organic solvents, obviated need for demanding process conditions (such as cooling condition) and apparatus, low cost, and facilitated applicability in industrialized manufacturing. This solid preparation provides great stability, solubility, and bioavailability, reduced individual differences, and reduced content of related substances. 1. A preparation method of aripiprazole type I microcrystal , which comprises the following steps: dissolving aripiprazole in an acidic solution having an acidifier , acquiring a medicament-having acid solution; adding an alkalizer while stirring , then adding water or aqueous ethanol of 10 to 60 wt % while stirring , and separating a precipitated aripiprazole type-I microcrystal.2. The preparation method of aripiprazole type I microcrystal according to claim 1 , wherein: said aripiprazole is aripiprazole type I microcrystal claim 1 , aripiprazole type II microcrystal or amorphous aripiprazole.3. The preparation method of aripiprazole type I microcrystal according to claim 1 , wherein: said acidifier is one or more among hydrochloric acid claim 1 , lactic acid and malic acid; a dosage of said acidifier is 1˜1.2 times over a minimum dosage which can completely dissolve the aripiprazole.4. The preparation method of ...

Modulators of atp-binding cassette transporters

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

2(1H)-QUINOLINONE DERIVATIVE

Provided are: useful novel compounds that exhibit antibacterial activity based on their actions for inhibiting GyrB of DNA gyrase and ParE of topoisomerase IV; and 2(1H)-quinolinone derivatives represented by formula [1]: 2. The compound according to wherein Z is NH—R claim 1 , a Calkyl group or a hydroxy group and Ris a Calkyl group claim 1 , or a pharmaceutically acceptable salt thereof.3. The compound according to wherein Z is NH—R claim 2 , an ethyl group or a hydroxy group and Ris a methyl group claim 2 , or a pharmaceutically acceptable salt thereof.4. The compound according to wherein Z is NH—Rand Ris a methyl group claim 3 , or a pharmaceutically acceptable salt thereof.5. The compound according to wherein T claim 4 , U claim 4 , V and W are each C—R claim 4 , or a pharmaceutically acceptable salt thereof.6. The compound according to wherein Lis —CONR— claim 5 , —COO— or —(CH)NR— claim 5 , or a pharmaceutically acceptable salt thereof.7. The compound according to wherein Lis —CONR— claim 6 , or a pharmaceutically acceptable salt thereof.8. The compound according to wherein Ris a hydrogen atom claim 7 , or a pharmaceutically acceptable salt thereof.9. The compound according to wherein Lis a bond or a group selected from the group consisting of a bond claim 8 , a methylene group or an ethylene group claim 8 , a piperidinediyl group claim 8 , a pyrrolidinediyl group claim 8 , and an azetidinediyl group claim 8 , or a pharmaceutically acceptable salt thereof.10. The compound according to wherein Lis a bond or an ethylene group claim 9 , or a pharmaceutically acceptable salt thereof.11. The compound according to wherein Lis a bond claim 10 , or a pharmaceutically acceptable salt thereof.14. The compound according to wherein each Ris independently a hydrogen atom claim 13 , a fluorine atom or a hydroxy group claim 13 , or a pharmaceutically acceptable salt thereof.15. The compound according to wherein U is C—F or C—H claim 13 , T and V are each C—H claim 13 , and ...

HAPTENS OF ARIPIPRAZOLE

The invention relates to compounds of Formula I, wherein R, R, and Rare defined in the specification, useful for the synthesis of novel conjugates and immunogens derived from aripiprazole. The invention also relates to conjugates of an aripiprazole hapten and a protein. 6. The conjugate of claim 5 , wherein the immunogenic carrier is a protein.7. The conjugate of claim 6 , wherein the protein is keyhole limpet hemocyanin claim 6 , bovine thyroglobulin claim 6 , or ovalbumin.9. The conjugate of claim 8 , wherein the immunogenic carrier is a protein.10. The conjugate of claim 9 , wherein the protein is keyhole limpet hemocyanin claim 9 , bovine thyroglobulin claim 9 , or ovalbumin.12. The conjugate of claim 11 , wherein the immunogenic carrier is a protein.13. The conjugate of claim 12 , wherein the protein is keyhole limpet hemocyanin claim 12 , bovine thyroglobulin claim 12 , or ovalbumin.15. The conjugate of claim 14 , wherein the immunogenic carrier is a protein.16. The conjugate of claim 15 , wherein the protein is keyhole limpet hemocyanin claim 15 , bovine thyroglobulin claim 15 , or ovalbumin.18. The conjugate of claim 17 , wherein the immunogenic carrier is a protein.19. The conjugate of claim 18 , wherein the protein is keyhole limpet hemocyanin claim 18 , bovine thyroglobulin claim 18 , or ovalbumin.21. The conjugate of claim 20 , wherein the immunogenic carrier is a protein.22. The conjugate of claim 21 , wherein the protein is keyhole limpet hemocyanin claim 21 , bovine thyroglobulin claim 21 , or ovalbumin.28. The product of claim 27 , wherein the immunogenic carrier is a protein.29. The product of claim 28 , wherein the protein is keyhole limpet hemocyanin claim 28 , bovine thyroglobulin claim 28 , or ovalbumin.31. The product of claim 30 , wherein the immunogenic carrier is a protein.32. The product of claim 31 , wherein the protein is keyhole limpet hemocyanin claim 31 , bovine thyroglobulin claim 31 , or ovalbumin.34. The product of claim 33 , ...

ANTI-ANGIOGENESIS COMPOUND, INTERMEDIATE AND USE THEREOF

Disclosed are an anti-abnormal proliferation of angiogenesis compound represented by formula I, use and intermediate thereof. The compound has good effect against abnormal proliferation of angiogenesis, and the activity of the compound is produced by inhibiting VEGFR2. The compound can be used for treating diseases, such as wet macular degeneration, inflammation, malignant tumor and the like, caused by abnormity of angiogenesis and protein kinases such as VEGFR2, FGFR2 and the like. 2. The compound and the pharmaceutically acceptable salt or prodrug thereof according to claim 1 , wherein Ris selected from H claim 1 , amino or —(CH)NHR claim 1 , wherein n=1-3 claim 1 , Ris H or C1-2 alkyl; Ris selected from H or C1-2 alkyl; R claim 1 , Rand Rare each independently selected from halogen claim 1 , C1-2 alkyl or halogen substituted alkyl; and Ris selected from H or halogen;{'sub': 2', '3, 'or, Rand Rtogether with the carbon atom connecting them form substituted or unsubstituted 5- or 6-membered ring having 1 nitrogen atom, wherein the substituent is C1-3 alkyl.'}3. The compound and the pharmaceutically acceptable salt or prodrug thereof according to claim 2 , wherein Ris selected from amino or —(CH)NHR; or claim 2 , Rand Rtogether with the carbon atom connecting them form substituted or unsubstituted 5- or 6-membered ring having 1 nitrogen atom claim 2 , wherein the substituent is C1-3 alkyl.4. The compound and the pharmaceutically acceptable salt or prodrug thereof according to claim 2 , wherein at least one of R claim 2 , Rand Ris amino claim 2 , and the rest are H; R claim 2 , Rand Rare the same and are selected from F or Cl; and Ris H.612.-. (canceled)13. A pharmaceutical composition claim 1 , comprising an effective amount of the compound and a pharmaceutically acceptable salt or prodrug thereof according to .14. The pharmaceutical composition according to claim 13 , wherein the composition is an ophthalmic preparation.16. The compound and the pharmaceutically ...

MUTANT IDH1 INHIBITORS USEFUL FOR TREATING CANCER

Compounds of Formula I and Formula II and the pharmaceutically acceptable salts thereof are disclosed The variables A, B, Y, Z, X, X, Rand Rare disclosed herein. The compounds are useful for treating cancer disorders, especially those involving mutant IDH1 enzymes. Pharmaceutical compositions containing compounds of Formula I or Formula II and methods of treatment comprising administering compounds of Formula I and Formula II are also disclosed. 23-. (canceled)4. The compound or salt of wherein{'sup': 1', '5', '5', '6', '5', '5', '6', '5', '6, 'sub': 1', '6', '1', '6', '1', '6', '1', '2', '1', '2', '0', '6', '3', '6', '0', '6', '3', '6', '0', '2', '0', '2', '0', '6', '2', '0', '6', '1', '6', '0', '6', '0', '6, 'Ris a phenyl or pyridyl substituted by 0-3 substituents independently chosen from hydroxyl, halogen, cyano, nitro, C-Calkyl, C-Calkylthio, C-Calkoxy, C-Chaloalkyl, C-Chaloalkoxy, -(C-Calkyl)C-Ccycloalkyl, —O-(C-Calkyl) C-Ccycloalkyl, -(C-Calkyl)phenyl, —O-(C-Calkyl)phenyl, -(C-Calkyl)COR, -(C-Calkyl)C(O)NRR, -(C-Calkyl)OR, -(C-Calkyl)NRR, and -(C-Calkyl)NRC(O)R;'}{'sup': '2', 'sub': 1', '6', '2', '6', '2', '6', '0', '6, 'Ris C-Calkyl, C-Calkenyl, C-Calkynyl, or -(C-Calkyl)cycloalkyl;'}{'sup': 3', '7', '8, 'Ris —C(O)NRR;'}{'sup': '4', 'sub': 1', '6, 'Ris hydrogen or C-Calkyl;'}{'sub': 1', '6', '1', '6', '1', '6', '1', '6', '0', '6', '0', '6', '0', '6', '2', '0', '6, 'sup': 5', '5', '6, 'A is a monocyclic heteroaryl of 5 or 6 ring atoms having 1 to 4 ring atoms independently chosen from N, O, and S, wherein A is substituted with 0-2 substituents independently chosen from halogen, cyano, C-Calkyl, C-Calkoxy, C-Chaloalkyl, and C-Chaloalkoxy, -(C-Calkyl)cycloalkyl, —O(C-Calkyl)cycloalkyl, -(C-Calkyl)COR, and -(C-Calkyl)C(O)NRR; and'}{'sub': 1', '6', '1', '6', '1', '6', '1', '6', '0', '6', '0', '6', '0', '6', '0', '6', '0', '6', '0', '6', '0', '6', '2', '0', '6', '0', '6', '1', '6, 'sup': 9', '9', '10', '9', '10', '9, 'B is a phenyl or pyridyl substituted with 0-3 ...

Modulators of atp-binding cassette transporters

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

PYRIDIN-2(1H)-ONE QUINOLINONE DERIVATIVES AS MUTANT-ISOCITRATE DEHYDROGENASE INHIBITORS

The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula: 2. The compound of claim 1 , wherein A is CN.3. The compound of claim 2 , wherein B is C-Calkoxy or C-Calkyl.4. The compound of claim 3 , wherein B is methoxy.5. The compound of claim 3 , wherein B is C-Calkyl.6. The compound of claim 5 , wherein B is methyl.7. The compound of claim 1 , wherein A is H or F.13. The compound of claim 1 , claim 1 , claim 1 , claim 1 , or claim 1 , wherein Ris Me claim 1 , Et claim 1 , and cyclopropyl.15. The compound of claim 14 , wherein B is C-Calkoxy.16. The compound of claim 15 , wherein B is methoxy17. The compound of claim 1 , wherein Rand Rare H.18. The compound of claim 1 , wherein Ris H and Ris methyl.19. The compound of claim 1 , wherein Ris H and Ris (S)-methyl20. The compound of claim 1 , wherein Rand Rare halogen.21. The compound of claim 1 , wherein Ris F and Ris methyl.22. The compound of claim 1 , wherein Rand Rcan combine to form a C-Ccycloalkyl.23. The compound of claim 1 , wherein W claim 1 , W claim 1 , and Ware CH claim 1 , or CF.24. The compound of claim 1 , wherein Wor Wis N.25. The compound of claim 1 , wherein Ris halogen.26. The compound of claim 23 , wherein Ris chloro.27. The compound of claim 1 , wherein Ris H claim 1 , halogen claim 1 , or C-Calkoxy.28. The compound of claim 1 , wherein Ris C-Calkoxy substituted with heteroaryl or 3-to 8-membered heterocyclyl.35. The compound of selected from the group consisting of:4-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methoxybenzonitrile;4-{[(1R)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methoxybenzonitrile;4-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-3-methanesulfonylbenzonitrile;4-{[1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methoxybenzonitrile;4-({1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1 ...

Compositions of protein receptor tyrosine kinase inhibitors

The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and/or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF recptor TrkA.

HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF NEUROLOGICAL AND PSYCHOLOGICAL DISORDERS

Lactam compounds of Formula I and their use for the treatment of neurological and psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorder and insomnia is disclosed. 124-. (canceled)27. A pharmaceutical composition comprising the compound of claim 25 , and one or more pharmaceutically acceptable carriers or excipients.28. A pharmaceutical composition comprising the compound of claim 26 , and one or more pharmaceutically acceptable carriers or excipients.29. A method of treating schizophrenia comprising administering the compound of to a patient in need thereof.30. A method of treating bipolar disorder comprising administering the compound of to a patient in need thereof.31. A method of treating depression comprising administering the compound of to a patient in need thereof.32. A method of treating mania comprising administering the compound of to a patient in need thereof.33. A method of treating anxiety comprising administering the compound of to a patient in need thereof.36. A method of treating depression comprising administering the compound of to a patient in need thereof.37. A method of treating mania comprising administering the compound of to a patient in need thereof.38. A method of treating anxiety comprising administering the compound of to a patient in need thereof.39. A method of treating schizophrenia comprising administering the pharmaceutical composition of to a patient in need thereof.40. A method of treating bipolar disorder comprising administering the pharmaceutical composition of to a patient in need thereof.41. A method of treating depression comprising administering the pharmaceutical composition of to a patient in need thereof.42. A method of treating mania comprising administering the pharmaceutical composition of to a patient in need thereof.43. A method of treating anxiety comprising administering the pharmaceutical composition of to a patient in need thereof.44. A method of treating schizophrenia comprising ...

IDENTIFICATION OF COMPOUNDS THAT DISPERSE TDP-43 INCLUSIONS

Herein, compounds and compositions for use in treating diseases relating to inclusion formation and stress granules are described. Methods for screening for modulation of TDP-43 aggregation are also described. 136-. (canceled)40. The method of claim 37 , wherein the neurodegenerative disease is selected from Alzheimer's disease claim 37 , frontotemporal dementia claim 37 , FTLD-U claim 37 , amyotrophic lateral sclerosis (ALS) claim 37 , Huntington's chorea claim 37 , Creutzfeld-Jacob disease claim 37 , trinucleotide repeat diseases claim 37 , cerebral degenerative diseases presenile dementia claim 37 , senile dementia claim 37 , Parkinsonism linked to chromosome 17 (FTDP-17) claim 37 , progressive supranuclear palsy (PSP) claim 37 , Huntington's disease (HD) claim 37 , Pick's disease claim 37 , primary progressive aphasia claim 37 , corticobasal dementia claim 37 , Parkinson's disease claim 37 , Parkinson's disease with dementia claim 37 , dementia with Lewy bodies claim 37 , Down's syndrome claim 37 , multiple system atrophy claim 37 , spinal muscular atrophy (SMA) claim 37 , spinocerebellar ataxia claim 37 , spinal degenerative disease/motor neuron degenerative diseases claim 37 , Hallervorden-Spatz syndrome claim 37 , cerebral infarct claim 37 , cerebral trauma claim 37 , chronic traumatic encephalopathy claim 37 , and transient ischemic attack claim 37 , or any combination thereof.41. The method of claim 40 , wherein the neurodegenerative disease is selected from Alzheimer's disease claim 40 , frontotemporal dementia claim 40 , FTLD-U claim 40 , amyotrophic lateral sclerosis (ALS) claim 40 , and Huntington's chorea.42. The method of claim 37 , wherein viral infection is caused by a virus selected from the group consisting of West Nile virus claim 37 , Respiratory Syncitial Virus (RSV) claim 37 , herpes simplex virus 1 claim 37 , herpes simplex virus 2 claim 37 , Epstein-Barr virus (EBV) claim 37 , hepatitis virus A claim 37 , hepatitis virus B claim 37 , ...

Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”). 2. A process to control a pest claim 1 , said process comprising claim 1 , applying to a locus claim 1 , a pesticidally effective amount of a molecule according to . This Application is a continuation of, and claims the benefit of, U.S. nonprovisional application Ser. No. 15/679,415, which was filed Aug. 17, 2017, and which is now allowed; Ser. No. 15/679,415 is a divisional of, and claims the benefit of, U.S. nonprovisional application Ser. No. 15/092,650, which was filed Apr. 7, 2016, and is now U.S. Pat. No. 9,781,935; Ser. No. 15/092,650 claims the benefit of, and priority from, U.S. provisional application Ser. Nos. 62/148,809; 62/148814; 62/148818; 62/148824; 62/148830; and 62/148,837; all of which were filed on Apr. 17, 2015. The entire contents of all of the above-identified applications are hereby incorporated by reference into this Application.This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides.“Many of the most dangerous human diseases are transmitted by insect vectors” (Rivero et al.). “Historically, malaria, dengue, yellow ...

COMPOUNDS, COMPOSITIONS, AND METHODS FOR SELECTIVELY INHIBITING B-GLUCURONIDASES AND ALLEVIATING SIDE EFFECTS ASSOCIATED WITH DRUG TREATMENT INDUCED DIARRHEA

The present disclosure describes compounds and compositions that inhibit β-glucuronidase activity, and methods for attenuating the side effects of one or more drugs and improving the efficacy of drugs by administration of selective β-glucuronidase inhibitors. 13. The compound of any one of - , wherein Ris selected from substituted Calkyl or Calkylaminoalkyl.14. The compound of claim 13 , wherein the Calkyl is substituted witha. a substituted or unsubstituted 3- to 10-membered ring, optionally having one or more heteroatoms selected from N, O, or S, and optionally having one or more degrees of unsaturation, or{'sub': x', 'x', '1-6, 'b. OC(O)R, wherein Ris Calkyl.'}15. The compound of any one of claim 13 , claim 13 , claim 13 , claim 13 , claim 13 , claim 13 , claim 13 , claim 13 , claim 13 , or claim 13 , wherein Ris (L)R claim 13 , wherein Lis a Calkylene claim 13 , n is 1 claim 13 , and Ris OR claim 13 , wherein Ris hydrogen.16. The compound of any one of - claim 13 , wherein Ris (L)R claim 13 , n is 0 claim 13 , and Ris a substituted or unsubstituted 3- to 10-membered ring claim 13 , optionally having one or more heteroatoms selected from N claim 13 , O claim 13 , or S claim 13 , and optionally having one or more degrees of unsaturation.17. The compound of any one of claim 13 , claim 13 , claim 13 , claim 13 , claim 13 , claim 13 , claim 13 , claim 13 , claim 13 , or claim 13 , wherein Ris substituted Calkyl; Ris (L)R claim 13 , wherein Lis a Calkylene claim 13 , n is 1 claim 13 , and Ris OR claim 13 , wherein Ris hydrogen; and X is S.18. The compound of wherein the Calkyl is substituted witha. a substituted or unsubstituted 3- to 10-membered ring, optionally having one or more heteroatoms selected from N, O, or S, and optionally having one or more degrees of unsaturation, or{'sub': x', 'x', '1-6, 'b. OC(O)R, wherein Ris Calkyl.'}19. The compound of any one of claim 17 , claim 17 , claim 17 , claim 17 , claim 17 , claim 17 , claim 17 , claim 17 , claim 17 , or ...

SECONDARY ALCOHOL QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 6. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.7. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.8. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.9. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .10. The method of claim 9 , wherein the disease is selected from the group consisting of: inflammatory bowel diseases claim 9 , rheumatoid arthritis claim 9 , psoriasis claim 9 , chronic obstructive pulmonary disorder claim 9 , psoriatic arthritis claim 9 , ankylosing spondylitis claim 9 , neutrophilic asthma claim 9 , steroid resistant asthma claim 9 , multiple sclerosis claim 9 , and systemic lupus erythematosus.11. The method of claim 9 , wherein the disease is psoriasis.12. The method of claim 9 , wherein the disease is rheumatoid arthritis.13. The method of claim 10 , wherein the inflammatory bowel disease is ulcerative colitis.14. The method of claim 10 , wherein the inflammatory bowel disease is Crohn's disease.15. The method of claim 9 , wherein the disease is multiple sclerosis.16. The method of claim 9 , wherein the disease is neutrophilic asthma.17. The method of claim 9 , wherein the disease is steroid resistant asthma.18. The method of claim 9 , wherein the disease is psoriatic arthritis.19. The method of claim 9 , wherein the disease is ankylosing spondylitis.20. The method of claim 9 , wherein the disease is systemic lupus erythematosus.21. The method of claim 9 , wherein the disease is chronic obstructive pulmonary disorder.22. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising ...

Processes for making alkylated arylpiperazine and alkylated arylpiperidine compounds including novel intermediates

Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively wherein, R 1 and R 2 are individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NR 3 R 4 , OR 5 , or SR 5 , where R 3 and R 4 are individually selected from acyl or sulfonyl, and where R 5 is aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.

Screening methods for spinal muscular atrophy

Disclosed herein are compositions and methods for treatment of spinal muscular atrophy (SMA). In certain embodiments, compounds are provided that increase full-length survival of motor neuron (SMN) protein production by an SMN2 gene.

HAPTENS OF ARIPIPRAZOLE

The invention relates to compounds of Formula I, wherein R, R, and Rare defined in the specification, useful for the synthesis of novel conjugates and immunogens derived from aripiprazole. The invention also relates to conjugates of an aripiprazole hapten and a protein. 110.-. (canceled) This application is a continuation of U.S. application Ser. No. 15/342,772, filed Nov. 3, 2016, and published Mar. 16, 2017, as US 2017/0072061, which is a divisional of U.S. application Ser. No. 13/970,650, filed Aug. 20, 2013, and issued Nov. 29, 2016, as U.S. Pat. No. 9,504,682, which claims the benefit of U.S. Provisional Application No. 61/691,450, filed Aug. 21, 2012, all of which are hereby incorporated by reference in their entireties.The invention relates to the field of immunoassays for determining the presence of aripiprazole in human biological fluids.Schizophrenia is a chronic and debilitating psychiatric disorder affecting approximately 0.45-1% of the world's population (van Os, J.; Kapur, S. “Schizophrenia” Lancet 2009, 374, 635-645). The principal goals of treatment are to achieve sustained remission from psychotic symptoms, reduce the risk and consequences of relapse, and improve patient functioning and overall quality of life. While many patients with schizophrenia are able to achieve symptom stability with the available antipsychotic medications, poor adherence to medication is a common reason for relapse with daily administered oral medications. Several studies (Abdel-Baki, A.; Ouellet-Plamondon, C.; Malla, A. “Pharmacotherapy Challenges in Patients with First-Episode Psychosis” Journal of Affective Disorders 2012, 138, S3-S14) investigating the outcomes of non-compliance have shown that patients with schizophrenia who do not take their medication as prescribed have higher rates of relapse, hospital admission and suicide as well as increased mortality. It is estimated that 40 to 75% of patients with schizophrenia have difficulty adhering to a daily oral treatment ...

FUSED-BICYCLIC ARYL QUINOLINONE DERIVATIVES AS MUTANT-ISOCITRATE DEHYDROGENASE INHIBITORS

The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula: 127-. (canceled)28. A pharmaceutical composition comprising a compound , or a pharmaceutically acceptable salt thereof , selected from:3-{[(1,3-benzoxazol-4-yl)amino]methyl}-6-chloro-1,2-dihydroquinolin-2-one;6-chloro-3-{[(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(2-oxo-2H-chromen-6-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(isoquinolin-3-yl)amino]methyl}-1,2-dihydroquinolin-2-one;4-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}naphthalene-1-carbonitrile;6-chloro-3-{[(quinolin-8-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(2,3-dihydro-1-benzofuran-7-yl)amino]methyl}-1,2-dihydroquinolin-2-one;7-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;7-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-3,4-dihydro-2H-1,4-benzoxazin-3-one;3-{[2-(1H-1,3-benzodiazol-5-yl)-1H-1,3-benzodiazol-5-yl]amino}methyl)-6,7-dimethoxy-1,2-dihydroquinolin-2-one;6-chloro-3-{[(2-oxo-2,3-dihydro-1H-indol-6-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(isoquinolin-8-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(3,4-dihydro-2H-1-benzopyran-8-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(6-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(3-methyl-1H-indazol-6-yl)amino]methyl}-1,2- ...

Alpha,Beta-UNSATURATED AMIDE COMPOUND

An object of the present invention is to provide an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like. The α,β-unsaturated amide compound represented by the following formula (I) or a pharmaceutically acceptable salt or the like thereof has anticancer activity and the like: [wherein, “A” represents optionally substituted heterocyclic diyl, R 1 represents hydrogen atom or optionally substituted lower alkyl, R 2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents —O—, —S—, —SO 2 —, —NR X1 — (wherein, R X1 represents hydrogen atom or lower alkyl), —CHR X2 — (wherein, R X2 represents hydrogen atom or hydroxy), —CH═CH—, −CO— or —NH—CO—, and n1 and n2 are the same or different, and each represents 0 or 1].

ROR MODULATORS AND THEIR USES

The invention relates to ROR modulators; compositions comprising an effective amount of a ROR modulator; and methods for treating or preventing diseases associated with ROR. 2. The compound of claim 1 , wherein A is aryl.3. The compound of claim 2 , wherein A is phenyl.4. The compound of claim 1 , wherein Rand Rare taken together to form a ring selected from the group consisting of pyrrolidine claim 1 , pyrrole claim 1 , pyrazole claim 1 , imidazole claim 1 , furan claim 1 , tetrahydrofuran claim 1 , piperidine claim 1 , pyridine claim 1 , pyrimidine claim 1 , oxazole claim 1 , isothiazole claim 1 , and thiazole.5. The compound of claim 4 , wherein the ring is pyrrolidine.6. The compound of claim 4 , wherein the ring is tetrahydrofuran.7. The compound of claim 1 , wherein Rand Rare taken together to form a carbonyl group.8. The compound of claim 1 , wherein Ris H and Ris H or CH.17. A pharmaceutical composition comprising a compound of or and a pharmaceutically acceptable carrier.18. A method of treating any disease mediated by Retinoic Acid Receptor-Related Orphan Receptor (ROR)α and/or RORγ claim 1 , said method comprising administering an effective amount of a compound of or to a patient in need thereof.19. The method of claim 18 , wherein the disease is selected from the group consisting of angina pectoris claim 18 , myocardial infarction claim 18 , atherosclerosis claim 18 , cystic fibrosis claim 18 , gastritis claim 18 , autoimmune myositis claim 18 , giant cell arteritis claim 18 , Wegener's granulomatosis claim 18 , asthma claim 18 , chronic obstructive pulmonary disease claim 18 , rheumatoid arthritis claim 18 , juvenile rheumatoid arthritis claim 18 , allergen-induced lung inflammation claim 18 , allergy claim 18 , psoriasis claim 18 , psoriatic arthritis claim 18 , colitis claim 18 , inflammatory bowel disease claim 18 , Crohn's disease claim 18 , ulcerative colitis claim 18 , Sjogren's syndrome claim 18 , dry eye claim 18 , optic neuritis claim 18 , ...

LOW HYGROSCOPIC ARIPIPRAZOLE DRUG SUBSTANCE AND PROCESSES FOR THE PREPARATION THEREOF

The present invention provides low hygroscopic forms of aripiprazole and processes for the preparation thereof which will not convert to a hydrate or lose their original solubility even when a medicinal preparation containing the anhydrous aripiprazole crystals is stored for an extended period. 1. Hydrate A of aripiprazole having a powder x-ray diffraction spectrum comprising characteristic peaks at 2θ=12.6°, 15.4°, 17.3°, 18.0°, 18.6°, 22.5°, and 24.8° using a Cu K x-ray. This application is a continuation of application Ser. No. 11/790,604, filed Apr. 26, 2007, now pending, which is a division of application Ser. No. 10/333,244, now abandoned, which is a  371 of International Application No. PCT/JP02/09858, filed Sep. 25, 2002, which claims priority of Japanese Application Nos. JP 2001-290645, filed Sep. 25, 2001, and JP 2001-348276, filed Nov. 14, 2001, and of Canadian Application No. CA 2379005, filed Mar. 27, 2002, the contents of all of which are incorporated by reference.The present invention relates to an improved form of aripiprazole having reduced hygroscopicity and processes for the preparation of this improved form.Aripiprazole, 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]-butoxy}-3,4-dihydro carbostyril or 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]-butoxy}-3,4-dihydro-2(1H)-quinolinone, is an atypical antipsychotic agent useful for the treatment of schizophrenia (U.S. Pat. Nos. 4,734,416 and 5,006,528). Schizophrenia is a common type of psychosis characterized by delusions, hallucinations and extensive withdrawal from others. Onset of schizophrenia typically occurs between the age of 16 and 25 and affects 1 in 100 individuals worldwide. It is more prevalent than Alzheimer's disease, multiple sclerosis, insulin-dependent diabetes and muscular dystrophy. Early diagnosis and treatment can lead to significantly improved recovery and outcome. Moreover, early therapeutic intervention can avert costly hospitalization.According to Example 1 of Japanese ...

NOVEL REVAMIPIDE PRODRUGS, PREPARATION METHOD AND USE THEREOF

Disclosed are a novel rebamipide prodrug, a method for preparing the same, and use thereof. Also, a pharmaceutical composition comprising the novel rebamipide prodrug as an active ingredient is provided. The rebamipide prodrug is increased 25-fold in absorption rate compared to rebamipide itself, and can be applied to the prophylaxis or therapy of gastric ulcer, acute gastritis, chronic gastritis, xerophthalmia, cancer, osteoarthritis, rheumatoid arthritis, or obesity. 2. The compound claim 1 , pharmaceutically acceptable salt claim 1 , isomer claim 1 , hydrate claim 1 , or solvate of claim 1 , wherein the compound is selected from the group consisting of:1) methyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;2) ethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;3) 3-methylbutyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;4) hexyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;5) 2-bromoethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;6) 2-hydroxyethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;7) methoxymethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;8) 2-methoxyethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;9) 2-vinyloxyethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;10) 2-acetoxyethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;11) 2-methylsulfanylethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;12) 2-phenylsulfanylethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;13) 2-methylamino ethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;14) 2-dimethylaminoethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate;15) 2-dimethylamino-1-methyl-ethyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl) ...

Bicyclic aryl sphingosine 1-phosphate analogs

Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphin-gosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.

Methods and Compositions for Inhibition of Bromodomain-Containing Proteins

The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders. 155-. (canceled)57. The method of claim 56 , wherein Ris substituted or unsubstituted aryl claim 56 , or substituted or unsubstituted heteroaryl.58. The method of claim 56 , wherein Lis —(CRR) claim 56 , wherein Rand Rare each hydrogen or methyl and nis 1 or 2.59. The method of claim 56 , wherein L-Ris methyl.60. The method of claim 56 , wherein Ris H.61. The method of claim 56 , wherein Ris H.62. The method of claim 56 , wherein Ris H.65. The method of claim 56 , wherein:{'sub': 1C', '10C', '11C', 'nC', '10C', '11C', 'C, 'Lis —(CRR)wherein Rand Rare independently selected from hydrogen and methyl; and nis 1 or 2;'}{'sub': 2C', '4C, 'L-Ris methyl;'}{'sub': 1C', '1-6, 'Ris Calkyl, halogen-substituted phenyl, unsubstituted phenyl, or unsubstituted 5-7 membered heteroaryl, wherein the heteroaryl includes 1, 2, or 3 heteroatoms selected from nitrogen, oxygen, and sulfur;'}{'sub': '2C', 'Ris hydrogen;'}{'sub': '3C', 'Ris hydrogen; and'}{'sub': '8C', 'Ris hydrogen.'}66. The method of claim 56 , wherein Ris selected from substituted or unsubstituted aryl claim 56 , or substituted or unsubstituted heteroaryl; Rand Rare hydrogen; Ris selected from substituted or unsubstituted aryl claim 56 , or substituted or unsubstituted heteroaryl; Ris selected from substituted or unsubstituted aryl claim 56 , or substituted or unsubstituted heteroaryl; Lis —(C—RR)— wherein Rand Rare independently selected from hydrogen and methyl and nis 1 or 2; and Lis —(CRR)— claim 56 , wherein n is 0 claim 56 , 1 claim 56 , 2 claim 56 , or 3.68. The method of claim 56 , wherein the compound is 4-(benzylamino)-6-(3 claim 56 ,5-dimethylisoxazol-4-yl)-1-methylquinolin-2(1H)-one ...

Agents And Methods For Treating Ischemic And Other Diseases

This invention relates to compounds that modulate TRPM7 protein activity and use of the same for treatment or prophylaxis of ischemia, cancer, pain or glaucoma. 146-. (canceled)48. The compound of claim 47 , wherein J is O.49. The compound of claim 47 , wherein X′ is C-Calkyl.50. The compound of claim 49 , wherein X′ is pentyl claim 49 , butyl claim 49 , propyl claim 49 , ethyl or methyl.51. The compound of claim 50 , wherein X′ is n-propyl.52. The compound of claim 51 , wherein Y and Y′ are each independently selected from the group consisting of hydroxyl claim 51 , C-Calkoxy claim 51 , C-Calkyl claim 51 , amino claim 51 , C-Calkylamino claim 51 , mono- or di-(C-C) alkylamino claim 51 , mono- or di-(C-C) alkylaminoalkyl and halogen.53. The compound of claim 51 , wherein Y and Y′ are each independently selected from the group consisting of hydroxyl claim 51 , C-Calkoxy claim 51 , mono- or di-(C-C) alkylaminoalkyl and halogen.54. The compound of claim 51 , wherein Y is chloro or fluoro claim 51 , and Y′ is other than hydrogen.55. The compound of claim 51 , wherein Y is methoxy or ethoxy claim 51 , and Y′ is other than hydrogen.56. The compound of claim 51 , wherein Y is hydroxy claim 51 , and Y′ is other than hydrogen.57. The compound of claim 51 , wherein Y is mono- or di-(C-C) alkylaminoalkyl claim 51 , and Y′ is other than hydrogen.58. The compound of claim 57 , wherein Y is dimethylamino-(C-C) alkyl.59. The compound of claim 47 , wherein Y and Y′ are each independently selected from the group consisting of hydroxyl claim 47 , C-Calkoxy claim 47 , C-Calkyl claim 47 , amino claim 47 , C-Calkylamino claim 47 , mono- or di-(C-C) alkylamino claim 47 , mono- or di-(C-C) alkylaminoalkyl claim 47 , thiol claim 47 , cyano claim 47 , cyano(C-C)alkyl claim 47 , nitro and halogen.60. The compound of claim 47 , wherein Y″ is hydrogen and Y′ is selected from the group consisting of hydroxyl claim 47 , C-Calkoxy claim 47 , C-Calkyl claim 47 , amino claim 47 , C-Calkylamino ...

FUSED-BICYCLIC ARYL QUINOLINONE DERIVATIVES AS MUTANT-ISOCITRATE DEHYDROGENASE INHIBITORS

The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula (I) where A, B, U, V, Z, W, W, W, and R-Rare described herein. 3. The compound of claim 2 , wherein Ris methyl claim 2 , ethyl claim 2 , isopropyl claim 2 , or isobutyl.5. The compound of claim 4 , wherein Ris methyl claim 4 , ethyl claim 4 , isopropyl claim 4 , or isobutyl.6. The compound of claim 1 , wherein Rand Rare H.7. The compound of claim 1 , wherein Ris H and Ris methyl.8. The compound of claim 1 , wherein Ris H and Ris (S)-methyl.9. The compound of claim 1 , wherein Rand Rare halogen.10. The compound of claim 1 , wherein Ris F and Ris methyl.11. The compound of claim 1 , wherein Rand Rcan combine to form a C-Ccycloalkyl.12. The compound of any of the foregoing claims claim 1 , wherein W claim 1 , Wand Ware CH or CF.13. The compound of any of the foregoing claims claim 1 , wherein W claim 1 , W claim 1 , or Wis N.14. The compound of any of the foregoing claims claim 1 , wherein Ris halogen.15. The compound of claim 14 , wherein Ris chloro.16. The compound of any of the foregoing claims claim 14 , wherein Ris H or C-Calkoxy.17. The compound of any of the foregoing claims claim 14 , wherein Ris C-Calkoxy substituted with heteroaryl or C-Cheterocyclyl.18. The compound of selected from the group consisting of:3-{[(1,3-benzoxazol-4-yl)amino]methyl}-6-chloro-1,2-dihydroquinolin-2-one;6-chloro-3-{[(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(2-oxo-2H-chromen-6-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)amino]methyl}-1,2-dihydroquinolin-2-one;6-chloro-3-{[(isoquinolin-3-yl)amino]methyl}-1,2-dihydroquinolin-2-one;4-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl) ...

THERAPEUTIC COMPOUNDS

The invention provides compounds and compositions that are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia. This is a divisional application of U.S. Non-Provisional application Ser. No. 15/121,324, filed on 24 Aug. 2016, which is a National Stage Application under 35 USC371(c) of International Application No. PCT/US15/017832, having an International Filing Date of 26 Feb. 2015, and which claims the benefit of priority to U.S. Provisional Application No. 61/945,020, filed on 26 Feb. 2014. The entire content of the applications referenced above are hereby incorporated by reference herein.This invention was made with government support under R15 CA139364 awarded by the National Institutes of Health. The government has certain rights in the invention.The human retinoid X receptors (hRXRs) consist of three identified isoforms (a, (3, y) that function as transcription promoters often in partnership with other members of a larger nuclear receptor (NR) family of transcription regulators including the thyroid receptor (TR), the vitamin D receptor (VDR), the liver X receptor (LXR), the peroxisome proliferator-activated receptor (PPAR), and the retinoic acid receptor (RAR). While 9-cis-retinoic acid (9-cis-RA) and docosahexaenoic acid (DHA) have been shown to bind to hRXRs and promote RXR element (RXRE) regulated transcription (i.e. function as RXR agonists), it is still unclear if RXR has a bona fide endogenous molecular ligand. RXR has been described as the central NR regulator, because it often plays a critical role, either as a permissive or non-permissive partner, in heterodimer complexes that must be formed with the other NRs to regulate their respective response elements.Recent studies have identified several RXR-selective-binding molecular ligands (rexinoids) that can modulate not only RXRE regulated transcription but also the heterodimer regulated transcription of other ...

METHOD OF MODULATING STRESS-ACTIVATED PROTEIN KINASE SYSTEM

Disclosed are methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of at least one p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the at least one p38 MAPK by the compound. Also disclosed are derivatives of pirfenidone. These derivatives can modulate a stress activated protein kinase (SAPK) system. 1. (canceled)3. The compound of claim 2 , wherein Ris selected from the group consisting of substituted C-Calkyl claim 2 , C-Chaloalkyl claim 2 , C-Chydroxyalkyl claim 2 , and hydroxyl.4. The compound of claim 3 , wherein Ris selected from C-Chaloalkyl.5. The compound of claim 2 , wherein Ris selected from hydrogen or C-Calkyl.6. The compound of claim 2 , wherein X claim 2 , X claim 2 , X claim 2 , X claim 2 , and Xare independently selected from H and halogen.8. A pharmaceutical composition comprising a compound of claim 2 , and pharmaceutically acceptable excipients.9. A method for treating or ameliorating fibrosis comprising administering a therapeutically effective amount of a compound of to a subject in need thereof.11. The method of claim 10 , wherein at least one of X claim 10 , X claim 10 , X claim 10 , X claim 10 , and Xis not H.12. The method of claim 10 , wherein Ris selected from the group consisting of alkenyl claim 10 , C-Chaloalkyl claim 10 , C-Cnitroalkyl claim 10 , C-Cthioalkyl claim 10 , C-Calkoxy claim 10 , phenyl claim 10 , substituted phenyl claim 10 , halogen claim 10 , hydroxyl claim 10 , and C-Calkoxyalkyl.13. The method of claim 10 , wherein Ris selected from the group consisting of substituted C-Calkyl claim 10 , C-Chaloalkyl claim 10 , C-Calkoxy claim 10 , phenyl claim 10 , substituted phenyl claim 10 , halogen claim 10 , and hydroxyl.14. The method of claim 10 , wherein Ris selected from the group consisting of C-Chaloalkyl claim 10 ...

Method for producing optically active tetrahydroquinolines

Provided are a novel chiral iridium(III) complex; and a method for producing optically active 2-substituted-1,2,3,4-tetrahydroquinolines from 2-substituted-quinolines with the use of the chiral iridium(III) complex through a more economical and easy production process. The disclosed method for producing optically active 2-substituted-1,2,3,4-tetrahydroquinolines comprises reducing a quinoline compound represented by formula [I]: in the presence of a hydrogen donor compound and an iridium (III) complex having a chiral prolinamide compound as a ligand to give an optically active 2-substituted-1,2,3,4-tetrahydroquinoline represented by formula [II]:

SUBSTITUTED OXOPYRIDINE DERIVATIVES AND USE THEREOF AS FACTOR XIA/PLASMA

The invention relates to substituted oxopyridine derivatives and to processes for their preparation, and also to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and oedemas, and also ophthalmic disorders. 5. A pharmaceutical composition comprising the Compound according to for the treatment and/or prophylaxis of diseases.6. (canceled)7. A method of treating and/or for prophylaxis of thrombotic or thromboembolic disorders in a patient comprising administering a therapeutically effective amount of a compound according to to a patient in need thereof.8. A method of treating and/or prophylaxis of ophthalmic disorders in a patient comprising administering a therapeutically effective amount of the compound according to to a patient in need thereof.9. A method of treating and/or prophylaxis of hereditary angioedema or inflammatory disorders of the intestine claim 1 , or Crohn's disease or ulcerative colitis claim 1 , comprising administering a therapeutically effective amount of a compound according to to a patient in need thereof.10. A pharmaceutical composition comprising a compound according to in combination with a pharmaceutically suitable excipient.11. A method of treating and/or prophylaxis of thrombotic or thromboembolic disorders in a patient comprising administering a therapeutically effective amount of a pharmaceutical composition according to .12. A method of treating and/or prophylaxis of ophthalmic disorders in a patient comprising administering a therapeutically effective amount of a pharmaceutical composition according to .13. A method of treating and/or prophylaxis of hereditary angioedema or inflammatory disorders of the intestine claim 10 , or Crohn's disease or ulcerative colitis in a patient comprising administering a therapeutically effective amount of a pharmaceutical composition according to .14. Method for combating ...

SMALL MOLECULE MODULATORS OF HUMAN STING

The present invention relates to compounds of formula (I). The compounds may be used to modulate the Stimulator of Interferon Genes (STING) protein and thereby treat diseases such as cancer and microbial infections. 2. A compound according to claim 1 , wherein Xis CR claim 1 , Xis CRand Xis CR.3. A compound according to claim 1 , wherein one or two of X claim 1 , Xand Xis N.4. A compound according to any preceding claim claim 1 , wherein R claim 1 , Rand Rare each H.5. A compound according to any preceding claim claim 1 , wherein X is O claim 1 , S or CRR.6. A compound according to claim 5 , wherein X is S or CRR.7. A compound according to any preceding claim claim 5 , wherein at least one of Rand Ris an optionally substituted C-Calkyl claim 5 , halogen claim 5 , H claim 5 , a C-Ccycloalkyl or C-Cpolyfluoroalkyl.8. A compound according to claim 7 , wherein both Rand Rare H.9. A compound according to any preceding claim claim 7 , wherein n is 1.10. A compound according to any preceding claim claim 7 , wherein at least one of Rand Ris H.11. A compound according to claim 10 , wherein both Rand Ris H.12. A compound according to claim 10 , wherein one of Rand Ris H and the other is an optionally substituted C-Calkyl or an optionally substituted C-Calkenyl.13. A compound according to any preceding claim claim 10 , wherein Q is C═O claim 10 , SOor CRR.14. A compound according to claim 13 , wherein Q is C═O.15. A compound according to any preceding claim claim 13 , wherein L is C═O or SO claim 13 , an optionally substituted C-Calkyl claim 13 , —CHC(O)— or —CHCONH—.16. A compound according to claim 15 , wherein L is —CH— claim 15 , —CHCH— claim 15 , —CHCHCH— claim 15 , C(Me)H claim 15 , CFor C(H)F.17. A compound according to any preceding claim claim 15 , wherein Ris a mono or bicyclic optionally substituted C-Caryl claim 15 , a mono or bicyclic optionally substituted 5 to 10 membered heteroaryl claim 15 , an optionally substituted C-Ccycloalkyl or an optionally substituted ...

MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS

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

Antibodies to aripiprazole haptens and use thereof

Disclosed is an antibody which binds to aripiprazole, which can be used to detect aripiprazole in a sample such as in a competitive immunoassay method. The antibody can be used in a lateral flow assay device for point-of-care detection of aripiprazole, including multiplex detection of aripiprazole, olanzapine, quetiapine, and risperidone in a single lateral flow assay device.

Improved Process for the Preparation of Aripiprazole with Reduced Particle Size

The present invention relates to process for preparation of Aripiprazole with reduced particle size having dehydro impurity less than 0.1%. 2. The process as claimed in claim 1 , wherein polar aprotic solvent is dimethyl sulfoxide.3. The process as claimed in claim 1 , wherein non polar solvent is toluene.4. A process for purification of Aripiprazolewhich comprises:i) dissolve Aripiprazole in aprotic solvent,ii) heat the step i) reaction mixture,iii) cool the reaction mixture,iv) add polar solvent to precipitate,v) heat the obtained step iv) precipitate up to dissolve,vi) filter the compound in hot condition.5. The process as claimed in claim 4 , wherein polar aprotic solvent of step i) is selected from dimethyl formamide claim 4 , 1-methyl-2-pyrrolidinone claim 4 , hexamethylphosphoramide claim 4 , hexamethyl phosphorus triamide or dimethyl sulfoxide.6. The process as claimed in claim 5 , wherein polar aprotic solvent of step i) is dimethyl sulfoxide.7. The process as claimed in claim 4 , wherein polar solvent of step iv) is selected from methanol claim 4 , ethanol claim 4 , isopropyl alcohol claim 4 , isobutyl alcohol or tertiary-butyl alcohol.8. The process as claimed in claim 7 , wherein polar solvent of step iv) is selected from methanol.9. A process for preparation of Aripiprazole having with average particle size less than 35 μm.which comprises:i) dissolve Aripiprazole in polar solvent,ii) reflux step i) reaction mixture,iii) add step ii) reaction mixture to pre-cooled ethanol,iv) cool reaction mixture,v) filter the obtained product.10. The process for preparation of Aripiprazole as claimed in having dehydro impurity less than 0.1%.11. The process as claimed in claim 4 , wherein polar aprotic solvent of step i) is dimethyl sulfoxide.12. The process as claimed in claim 4 , wherein polar solvent of step iv) is selected from methanol. The invention relates to an improved process for the preparation of Aripiprazole having formula (I)The invention also relates to ...

SHIP1 MODULATORS AND METHODS RELATED THERETO

Compounds of formula (II): 3. The compound of wherein:{'sup': 1', '8', '9, 'Ris —R—OR;'}{'sup': 2', '8', '9, 'Ris —R—OR;'}{'sup': 3', '8', '9', '11', '8', '9', '12', '8', '9', '9a', '8', '9', '9a', '8', '9', '9a, 'sub': 2', '2', '2, 'Ris —R—N(R)C(O)R, —R—N(R)—R, —R—N(R)C(═NCN)N(R), —R—N(R)C(O)N(R)or —R—N(R)C(S)N(R);'}{'sup': 4a', '4b, 'Rand Rare each independently hydrogen, alkyl, alkenyl or alkynyl;'}{'sup': 4a', '4b', '7, 'or Ris hydrogen, alkyl, alkenyl or alkynyl and Ris a direct bond to the carbon to which Ris attached;'}{'sup': 5', '5, 'Ris alkyl or Ris a direct bond to the carbon at C14;'}{'sup': 6', '8', '9', '8', '9, 'sub': '2', 'Ris hydrogen, —R—ORor —R—N(R);'}{'sup': 7', '8', '9', '8', '9', '7', '4b', '7, 'sub': '2', 'Ris hydrogen, —R—OR, —R—N(R), or a direct bond to C15, provided that when Ris a direct bond to C15, Ris not a direct bond to the carbon to which Ris attached;'}{'sup': '8', 'each Ris independently a direct bond or a straight or branched alkylene chain;'}{'sup': '9', 'each Ris hydrogen, alkyl, optionally substituted aryl and optionally substituted aralkyl;'}{'sup': '9a', 'each Ris hydrogen, alkyl, optionally substituted aryl, optionally substituted aralkyl; optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl;'}{'sup': '11', 'Ris optionally substituted heteroaryl; and'}{'sup': '12', 'Ris optionally substituted heterocyclyl.'}4. The compound of wherein:{'sup': 1', '8', '9, 'Ris —R—OR;'}{'sup': 2', '8', '9, 'Ris —R—OR;'}{'sup': 3', '8', '9', '11', '8', '9', '12', '8', '9', '9a', '8', '9', '9a', '8', '9', '9a, 'sub': 2', '2', '2, 'Ris —R—N(R)C(O)R, —R—N(R)—R, —R—N(R)C(═NCN)N(R), —R—N(R)C(O)N(R)or —R—N(R)C(S)N(R);'}{'sup': 4a', '4b, 'Rand Rare each alkyl;'}{'sup': '5', 'Ris a direct bond to the carbon at C14;'}{'sup': '6', 'Ris hydrogen;'}{'sup': '7', 'Ris hydrogen;'}{'sup ...

ORGANIC REACTIONS CARRIED OUT IN AQUEOUS SOLUTION IN THE PRESENCE OF A HYDROXYALKYL(ALKYL)CELLULOSE OR AN ALKYLCELLULOSE

The present invention relates to a method of carrying out an organic reaction in aqueous solution in the presence of a hydroxyalkyl(alkyl)cellulose or an alkylcellulose. 1. A method of carrying out an organic reaction in a solvent containing at least 90% by weight , in particular at least 97% by weight , based on the total weight of the solvent , of water , which method comprises reacting the reagents in said solvent in the presence of a cellulose derivative which is selected from the group consisting of cellulose modified with one or more alkylene oxides or other hydroxyalkyl precursors , and alkylcellulose;where the organic reaction is not a polymerization or oligomerization reaction of olefinically unsaturated compounds.2. The method as claimed in claim 1 , where the cellulose derivative has a viscosity of from 1 to 150000 mPa·s claim 1 , in particular 2 to 100000 mPa·s claim 1 , specifically 2 to 10000 mPa·s claim 1 , determined as a 2% by weight aqueous solution claim 1 , relative to the weight of water.3. The method as claimed in claim 1 , where in the cellulose derivative 5 to 70% claim 1 , in particular 10 to 60% claim 1 , especially 15 to 50% of the hydrogen atoms in the hydroxyl groups of the cellulose on which the cellulose derivative is based are replaced by a hydroxyalkyl and/or alkyl group.4. The method as claimed in claim 1 , where the cellulose modified with one or more alkylene oxides or other hydroxyalkyl precursors is selected from the group consisting of hydroxyalkylcelluloses which are celluloses in which a part of the hydrogen atoms of the OH groups is replaced by a C-C-hydroxyalkyl group; hydroxyalkylalkylcelluloses which are celluloses in which a part of the hydrogen atoms of the OH groups is replaced by a C-C-hydroxyalkyl group and a part of the hydrogen atoms of the OH groups is replaced by a C-C-alkyl group; and alkylcelluloses which are celluloses in which a part of the hydrogen atoms of the OH groups is replaced by a C-C-alkyl group.5. ...

HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF NEUROLOGICAL AND PSYCHOLOGICAL DISORDERS

Lactam compounds of Formula I and their use for the treatment of neurological and psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorder and insomnia is disclosed. 3. A pharmaceutical composition comprising the compound of claim 1 , and one or more pharmaceutically acceptable carriers or excipients.4. A pharmaceutical composition comprising the compound of claim 2 , and one or more pharmaceutically acceptable carriers or excipients.5. A method of treating schizophrenia comprising administering the compound of to a patient in need thereof.6. A method of treating bipolar disorder comprising administering the compound of to a patient in need thereof.7. A method of treating depression comprising administering the compound of to a patient in need thereof.8. A method of treating mania comprising administering the compound of to a patient in need thereof.9. A method of treating anxiety comprising administering the compound of to a patient in need thereof.12. A method of treating depression comprising administering the compound of to a patient in need thereof.13. A method of treating mania comprising administering the compound of to a patient in need thereof.14. A method of treating anxiety comprising administering the compound of to a patient in need thereof.15. A method of treating schizophrenia comprising administering the pharmaceutical composition of to a patient in need thereof.16. A method of treating bipolar disorder comprising administering the pharmaceutical composition of to a patient in need thereof.17. A method of treating depression comprising administering the pharmaceutical composition of to a patient in need thereof.18. A method of treating mania comprising administering the pharmaceutical composition of to a patient in need thereof.19. A method of treating anxiety comprising administering the pharmaceutical composition of to a patient in need thereof.20. A method of treating schizophrenia comprising administering the ...

COMPOUNDS FOR OPTICALLY ACTIVE DEVICES

The present invention relates to novel compounds, particularly to compounds comprising a photoactive unit, said novel compounds being particularly suitable for ophthalmic devices as well as to ophthalmic devices comprising such compounds. 5. Compound according to claim 1 , wherein R claim 1 , Rand Rare H.6. Compound according to claim 1 , wherein Ris H and Ris a group of formula (II).7. Compound according to claim 1 , wherein those of R claim 1 , R claim 1 , R claim 1 , Rand Rthat are not Rare H.8. Compound according to claim 1 , wherein Sp is an alkanediyl or an alkylidene group claim 1 , wherein at least hydrogen has been replaced with R claim 1 , with Rbeing selected from the group consisting of OH claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , alkyl having from 1 to 10 carbon atoms claim 1 , partially or completely halogenated alkyl having from 1 to 10 carbon atoms claim 1 , alkoxy having from 1 to 10 carbon atoms claim 1 , and partially or completely halogenated alkoxy having from 1 to 10 carbon atoms.9. Compound according to claim 1 , wherein Sp is of formula (III){'br': None, 'sup': 7', '8, 'sub': 'b—', '—[C(R)(R)]\u2003\u2003(III)'}whereinb is at least 1; and{'sup': 7', '8', '16', '6', '7', '16, 'Rand Rare independently of each other H or R, provided that at least one of the Rand Rpresent is R, with le selected from the group consisting of OH, alkyl having from 1 to 10 carbon atoms, partially or completely halogenated alkyl having from 1 to 10 carbon atoms, alkoxy having from 1 to 10 carbon atoms, and partially or completely halogenated alkoxy having from 1 to 10 carbon atoms;'}{'sup': 7', '8', '7', '8, 'wherein if b is at least two, two neighboring groups C(R)(R) may be replaced by an alkenediyl or wherein if b is at least three, two neighboring groups C(R)(R) may be replaced by an alkyndiyl.'}10. Compound according to claim 1 , wherein Xis O.11. Compound according to claim 1 , wherein Xis O or S claim 1 , preferably O.12. Compound according to ...

O-GLCNAC TRANSFERASE (OGT) INHIBITORS AND USES THEREOF

The present invention provides inhibitors of O-GlcNAc transferase. Typically, the inhibitors are quinolinone-6-sulfonamides. The invention also provides pharmaceutical compositions thereof and methods for using the same in diabetes and complications thereof, metabolic diseases, neurodegenerative diseases, proliferative diseases (e.g., cancers), autoimmune diseases, and inflammatory diseases. 13. The compound of claim 1 , wherein Ris n-butyl.14. The compound of claim 1 , wherein Ris —CH-Ph.15. The compound of claim 1 , wherein each of Rand Ris independently optionally substituted thiophenyl-Calkylene claim 1 , optionally substituted phenyl-Calkylene claim 1 , or optionally substituted furanyl-Calkylene.16. The compound of claim 1 , wherein each of Rand Ris independently optionally substituted thiophenyl-Calkylene or optionally substituted furanyl-Calkylene.17. The compound of claim 1 , wherein each of Rand Ris independently optionally substituted thiophenyl-CH— claim 1 , optionally substituted phenyl-CH— claim 1 , or optionally substituted furanyl-CH—.18. is The compound of claim 1 , wherein each of Rand Rindependently optionally substituted thiophenyl-CH— or optionally substituted furanyl-CH—.19. The compound of claim 1 , wherein Ris hydrogen; and Ris Calkyl.20. The compound of claim 1 , wherein Ris hydrogen; and Ris methyl or ethyl.21. The compound of claim 1 , wherein Ris Calkyl; and Ris optionally substituted thiophenyl-Calkylene claim 1 , optionally substituted phenyl-Calkylene claim 1 , or optionally substituted furanyl-Calkylene.22. RThe compound of claim 1 , wherein Ris Calkyl; and is optionally substituted thiophenyl-Calkylene or optionally substituted furanyl-Calkylene.23. The compound of claim 1 , wherein Ris methyl; and Ris optionally substituted thiophenyl-CH— claim 1 , optionally substituted phenyl-CH— claim 1 , or optionally substituted furanyl-CH—.24. The compound of claim 1 , wherein Ris methyl; and Ris optionally substituted thiophenyl-CH— or ...

Activators of human pyruvate kinase

Disclosed are pyruvate kinase M2 activators which are compounds of Formula (I), including those of Formula (II), wherein A 1 , A 2 , L, R, R 1 to R 3 , X 1 to X 3 , k, n, and m are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer. A 1 -NR-L-A 2 (I)

Compound and Asymmetric Synthesis Reaction

A compound represented by the following General Formula (1): 2. (canceled) This application is a continuation application of International Application PCT/JP2012/081042 filed on Nov. 30, 2012 and designated the U.S., the entire contents of which are incorporated herein by reference.1. Field of the InventionThe present invention relates to a novel compound and an asymmetric synthesis reaction useful for synthesis of a group of compounds including the novel compound.2. Description of the Related ArtIt is said that carriers of hepatitis C virus (HCV) are about two million in Japan and about two hundred million in the world. About 50% of these patients develop chronic hepatitis, and about 20% of them suffer from liver cirrhosis or liver cancer after more than 30 years have passed since infection. Therefore, there has been a demand for establishment of an effective method for treating hepatitis C.Interferon therapy has been known as an effective method for eliminating HCV. However, patients to which interferon is effective are about ⅓ of all the patients.In view of this, further developments have been made and at present, a main anti-virus therapy is a PEG-interferon/ribavirin combination therapy using pegylated interferon and ribavirin (1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxyamide) in combination.However, patients to which even such a PEG-interferon/ribavirin combination therapy is significantly effective are about half of all the patients. Also, the HCV tends to mutate since it is a single-stranded RNA virus, which raises concerns that resistant viruses may arise by use of pharmaceutical drugs targeting viral proteins.Under such circumstances, demand has arisen for development of an anti-HCV agent targeting host's factors (human cells). The HCV uses the lipid raft portion for anchorage of growth, and hence serine palmitoyltransferase (SPT) inhibitor has been attracting attention, which shows an effect of inhibiting formation of the lipid raft in cells. NA255 ...

METHODS OF HYDROFLUORINATION

Some embodiments of the invention include inventive catalysts (e.g., compounds of Formula (I) or (Ia)). Other embodiments include compositions comprising the inventive catalysts. Some embodiments include methods of using the inventive catalysts (e.g., in hydrofluorination of an organic compound). Further embodiments include methods for making the inventive catalysts. Additional embodiments of the invention are also discussed herein. 1. A catalyst selected from {'br': None, 'sub': '4', 'i': 'x', 'MHSO-HF\u2003\u2003(Ia),'}, '(a) Formula (Ia)'} {'br': None, 'sub': 2', '4, 'i': 'x', 'MSO-HF\u2003\u2003(Ib), and'}, '(b) Formula (Ib)'} {'br': None, 'sup': 'a', 'sub': '4', 'i': 'x', 'MSO-HF\u2003\u2003(Ic);'}, '(c) Formula (Ic)'} [{'sup': +', '+', '+', '+', '+', '+, 'sub': '4', 'M is Li, Na, K, Rb, Cs, or NH,'}, {'sup': a', '2+', '2+', '2+', '2+', '2+', '2+', '2+', '2+', '2+', '2+,', '2+, 'Mis Be, Mg, Ca, Sr, Ba, Fe, Zn, Mn, Ni, Coor Cu, and'}, 'x is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16., 'wherein'}2. The catalyst of claim 1 , wherein the compound is selected from Formula (Ia).3. The catalyst of claim 1 , wherein x is 8 claim 1 , 9 claim 1 , 10 claim 1 , 11 claim 1 , 12 claim 1 , 13 claim 1 , 14 claim 1 , 15 claim 1 , or 16.4. The catalyst of claim 1 , wherein M is Na claim 1 , K claim 1 , or NH.5. The catalyst of claim 1 , wherein M is K.6. The catalyst of claim 1 , wherein the catalyst is KHSO-13HF.7. A composition comprising the catalyst of and a solvent.8. The composition of claim 7 , where the solvent is DCM (dichloromethane) claim 7 , DCE (1 claim 7 ,2 dichloroethane) claim 7 , dioxane claim 7 , EtO (diethylether) claim 7 , CHCN claim 7 , EtOAc (ethyl acetate) claim 7 , DMSO (dimethyl sulfoxide) claim 7 , DMF (dimethyl formamide) claim 7 , or toluene.9. The composition of claim 7 , where the solvent is DCM claim 7 , DCE claim 7 , or toluene.10. A method for hydrofluorination of an organic compound comprising one or more alkenes claim 7 , the ...

CONJUGATES OF HUPERZINE AND ANALOGS THEREOF

Compounds and compositions for treating neurodegenerative diseases are described. The compounds include a therapeutic agent covalently linked with huperzine or an analog thereof through a linker. Methods of preparing the compounds are described. Methods of treating a neurodegenerative disease by administering compounds and compositions including a therapeutic agent covalently linked with huperzine or an analog thereof are described. Methods for delivering a therapeutic agent by administering the therapeutic agent covalently linked to huperzine or an analog thereof are described. 2. The compound of claim 1 , wherein each therapeutic agent claim 1 , a therapeutic agent pro-drug claim 1 , or a therapeutic agent precursor is independently —V—W—X—Y—Z claim 1 , wherein V is bond claim 1 , —O— claim 1 , or —NH—;{'sub': 0', '6', '2', '6', '2', '6, 'W is —(C-C)alkyl-, —(C-C)alkenyl-; or —(C-C)alkynyl-;'}{'sub': '2', 'X is a bond, —O—, —NH—, —CO—, —(C═O)NH—, —NH—(C═O)—, —SO—, —(C═NH)—NH—, —(C═O)—O—, or —O(C═O)—;'}{'sub': 0', '6', '2', '6', '2', '6, 'Y is a —(C-C)alkyl-, —(C-C)alkenyl-; or —(C-C)alkynyl-;'}Z is a -quaternary amine, -cycloalkyl, -aryl, -heterocycle, or heteroaryl; andwherein each nitrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted.3. The compound of claim 1 , wherein -L- comprises at least one of a bond claim 1 , —O— claim 1 , —S— claim 1 , —NH— claim 1 ,{'sub': '2', '—N(alkyl)-, —C(O)—, —O(C═O)—, —C(═O)O—, —C(═S)O—, —C(═S)—, and —P(O)—.'}4. The compound of claim 1 , wherein only one of R claim 1 , R claim 1 , R claim 1 , Rand Ris -L-T; Ris selected from CH claim 1 , CF claim 1 , CFCF claim 1 , CFCFCF claim 1 , SOCH claim 1 , SOPh claim 1 , SOAr claim 1 , and SOH; and Ris selected from —(C-C)alkyl claim 1 , an aryl claim 1 , a cycloalkyl claim 1 , an alkenyl claim 1 , heterocycle claim 1 , and a heteroaryl.5. The compound of claim 1 , wherein one of R claim 1 , Rand Ris -L-T;{'sub': 1', '3', '3', '3', '3', ' ...

Process and intermediates for the preparation of benzo[b]thiophene compounds

A process for preparing compounds of formula (I), or a salt or solvate thereof, including Brexpiprazole, which process comprises cyclization of a compound of formula (II) or (III), or a salt or solvate thereof. The invention also refers to intermediates of said process.

COMPOUNDS FOR THE TREATMENT OF NEUROLOGIC DISORDERS

Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of certain neurologic disorders, including disorders related to NMDA receptor activity, including neuropsychiatric disorders, neurodegenerative disorders and other neurologic diseases, disorders and conditions including stroke, brain injury, epilepsy, neuropsychiatric disorders, mood disorders, chronic pain and related conditions. 8. A pharmaceutical composition comprising a compound of in a pharmaceutically acceptable carrier.9. A method of treatment or prophylaxis of neurologic disorders comprising administering to a host in need thereof an effective amount of a compound of claim 1 , optionally in a pharmaceutically acceptable carrier.10. The method of claim 9 , wherein the disorder is a neurodegenerative disorder.11. The method of claim 9 , wherein the neurologic disorder is neuropathic pain claim 9 , stroke claim 9 , traumatic brain injury claim 9 , epilepsy claim 9 , or other neurologic events.12. The method of claim 9 , wherein the neurologic disorder is associated with an increase or decrease in NMDA receptor activity.13. The method of claim 9 , wherein the neurologic disorder is a neuropsychiatric disorder.14. The method of claim 9 , wherein the neurologic disorder is a traumatic brain injury.15. The method of claim 9 , wherein the neurologic disorder is a concussion.16. The method of claim 9 , wherein the neurologic disorder is a blast injury.17. The method of claim 9 , wherein the compound is administered in combination with a pharmaceutically acceptable carrier.18. The method of claim 9 , wherein the compound is administered in combination or alternation with a second active agent. The present invention provides certain compounds useful in the treatment or prophylaxis of neurologic disorders, including neuropsychiatric disorders such as depression and anxiety, neurodegenerative disorders and other diseases and disorders of the neurological system. In certain ...

HISTONE METHYLTRANSFERASE INHIBITORS

The present disclosure provides certain angular tricyclic compounds that are histone methyltransferases G9a and/or GLP inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of G9a and/or GLP such as cancers and hemoglobinpathies (e.g., beta-thalassemia and sickle cell disease). Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds. 2. (canceled)3. (canceled)4. (canceled)5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein ring B is unsubstituted 5- or 6-membered cycloalkyl or 5- or 6-membered cycloalkyl substituted with 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 of R claim 1 , R claim 1 , R claim 1 , and Rwherein R claim 1 , R claim 1 , R claim 1 , and Rare independently selected from alkyl claim 1 , hydroxy claim 1 , alkoxy claim 1 , halo claim 1 , haloalkyl claim 1 , and haloalkoxy.6. (canceled)7. (canceled)8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein ring B is an unsubstituted 5- claim 1 , 6- claim 1 , or 7-membered saturated heterocyclyl or a 5- claim 1 , 6- claim 1 , or 7-membered saturated heterocyclyl substituted with 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 of R claim 1 , R claim 1 , R claim 1 , and Rwherein R claim 1 , R claim 1 , R claim 1 , and Rare independently selected from alkyl claim 1 , hydroxy claim 1 , alkoxy claim 1 , halo claim 1 , haloalkyl claim 1 , and haloalkoxy.9. (canceled)10. (canceled)11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein ring B is an unsubstituted 5- or 6-membered heteroaryl or a 5- or 6-membered heteroaryl substituted with 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 of R claim 1 , R claim 1 , R claim 1 , and Rwherein R claim 1 , R claim 1 , R claim 1 , and Rare independently selected from alkyl claim 1 , hydroxy claim 1 , alkoxy claim 1 , halo claim 1 , haloalkyl claim 1 , and haloalkoxy.12. The compound ...