2-[1', 2', 4'-ТРИАЗОЛ-3'-ИЛОКСИМЕТИЛЕН]АНИЛИДЫ, ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ И СРЕДСТВО БОРЬБЫ С ВРЕДОНОСНЫМИ ГРИБАМИ

Описываются новые соединения - 2-[1', 2', 4' - триазол-3'-илоксиметилен] анилиды общей формулы (I), где R1 означает C1 - C4 алкил, галоген, R2 означает водород, галоген, C1 - C4 алкил, C1 - C4 галогеналкил, C1 - C4 алкоксигруппу, R3 означает C1 - C4 алкил, фенил, незамещенный или замещенный 1 - 2 атомами галоида, С1 - C6 алкилом, C1 - C4 галоалкилом, нитро, C1 - C4 алкоксилом, C1 - C4 галоалкоксилом, фенилом или феноксигруппой, 2-пиридил, незамещенный или замещенный C1 - C4 галоалкилом, 2-пиразинил или пиридил, замещенный галоидом, R4 означает водород или C1 - C4 алкил, R5 означает C1 - C4 алкил, X означает кислород или NH, n = 0 или 1. Соединения проявляют биологическую активность и могут быть применены для борьбы с вредителями и вредными грибами с более высокой эффективностью. Описываются промежуточные продукты и средство борьбы с вредоносными грибами. 3 с.п.ф-лы, 3 табл.

ИНГИБИТОРЫ НЕПРИЛИЗИНА

Изобретение относится к соединениям, характеризующимся формулой XII, где значения R, R, R, Rи X определены в формуле изобретения, или к их фармацевтически приемлемой соли. Соединение по изобретению обладает ингибирующей активностью в отношении неприлизина (NEP) и предназначено для получения лекарственного средства для лечения гипертензии, сердечной недостаточности или заболевания почек. 7 н. и 21 з.п. ф-лы, 11 пр.

ПОЛУЧЕНИЕ 2-(5-БРОМ-4-(4-ЦИКЛОПРОПИЛНАФТАЛИН-1-ИЛ)-4H-1,2,4-ТРИАЗОЛ-3-ИЛТИО)УКСУСНОЙ КИСЛОТЫ

Изобретение относится к способу получения соединения формулы (III), включающему приведение в контакт соединения формулы (II), где R представляет собой -C-Салкил, с N-бромсукцинимидом (NBS) и растворителем. Изобретение также относится к способу получения соединения 4, к способу получения соединения 1, к реакционной смеси для получения соединения формулы (III), к реакционной смеси для получения соединения 4, к реакционной смеси для получения соединения 1, к соединению 2, к реакционной смеси для получения соединения формулы (II). Технический результат: предложен новый способ получения соединения 1, который может быть реализован в крупных масштабах. 8 н. и 11 з.п. ф-лы, 20 ил., 16 пр.

ПРОИЗВОДНЫЕ АЗОЛОВ

Изобретение относится к производному азола формулы (I) или его фармацевтически приемлемой соли, где Rпредставляет собой атом водорода или Салкил; Rпредставляет собой атом водорода или Салкил; Rпредставляет собой фенил или пиридил (где фенил или пиридил необязательно замещен одним или двумя фрагментами, выбранными из группы, состоящей из Салкокси, атомов галогена и трифторметила); каждый из Rи R, которые могут быть одинаковыми или различными, представляет собой атом водорода или Салкил (где Салкил необязательно замещен одним фрагментом, выбранным из группы, состоящей из гидрокси и Салкокси), или Rи Rвместе с соединяющим их атомом азота образуют 4-7-членный насыщенный или ненасыщенный гетероцикл, необязательно содержащий один циклический атом азота, кислорода или серы, помимо указанного выше соединяющего атома азота (где 4-7-членный насыщенный или ненасыщенный гетероцикл необязательно замещен одним или двумя фрагментами, выбранными из группы, состоящей из гидрокси, Салкила (где Салкил необязательно ...

ПРОИЗВОДНОЕ 1,2,4-ТРИАЗОЛОНА

Изобретение относится к производным 1,2,4-триазолона и их фармацевтически приемлемым солям. Соединения изобретения обладают антагонистической активностью в отношении рецептора V1b аргинина-вазопрессина. В формуле (1А):Rпредставляет Салкил (Салкил необязательно замещен одной-тремя группами, выбранными из группы, состоящей из гидрокси, атомов галогена, и Сциклоалкила), Сциклоалкил или 4-8-членный насыщенный гетероцикл, содержащий один гетероатом, выбранный из атома кислорода; Rпредставляет атом водорода; Rпредставляет фенил или пиридил (фенил или пиридил необязательно замещены одной или двумя группами, выбранными из группы, состоящей из Салкокси, атомов галогена, циано и Салкилсульфонила); Rи Rмогут быть одинаковыми или различными, и каждый представляет атом водорода или Cалкил (Салкил необязательно замещен одной гидрокси), или Rи Rнеобязательно, вместе с атомом азота, к которому они присоединены, образуют 4-8-членный насыщенный или ненасыщенный гетероцикл, необязательно содержащий один атом ...

ИНГИБИТОРЫ НЕПРИЛИЗИНА

Изобретение относится к соединению формулы I, где Rпредставляет собой -OR; Rпредставляет собой Н; X выбран из пиразола, триазола, бензотриазола, тетразола, оксазола, изоксазола, тиазола, пиридазина, пиримидина и пиридилтриазола; Rотсутствует или выбран из Н; галогена; -Салкилен-ОН; -Салкила; -Сциклоалкила; -Салкилен-О-Салкила; -C(O)R; -Салкилен-COOR; -С(О)NRR; -NHC(O)R; =O; фенила, необязательно замещенного одной или двумя группами, независимо выбранными из галогена, -ОСН, -NHC(O)CHи фенила; нафталенила; пиридинила; пиразинила; и R, когда он присутствует, соединен с атомом углерода; Rвыбран из Н; -ОН; -Cалкилен-COOR; -пиридинила; и фенила или бензила, необязательно замещенного одной или более группами, выбранными из галогена и -ОСН; и R, когда он присутствует, соединен с атомом углерода или атомом азота; а равен 0; или а равен 1; и Rвыбран из галогена и -CN; b равен 0; или b равен 1, и Rвыбран из Cl, F, -ОН, -СН, -ОСНи -CF; или b равен 2, и Rкаждый независимо выбран из галогена, -ОН, -СН ...

ЭНАНТИОМЕР 2-[2-(1-ХЛОРЦИКЛОПРОПИЛ)-3-(2-ХЛОРФЕНИЛ)-2-ГИДРОКСИПРОПИЛ]-2,4-ДИГИДРО-[1, 2,4]-ТРИАЗОЛ-3-ТИОНА И СПОСОБ ЕГО ПОЛУЧЕНИЯ

Новый (-)-энантиомер 2-[2-(1-хлорциклопропил)-3-(2-хлорфенил)-2-гидрокси-пропил]-2,4-дигидро-[1,2,4]-триазол-3-тиона формулы (I) и способ его получения. 1 з.п. ф-лы, 5 табл.

ПРОИЗВОДНОЕ ТРИАЗОЛА

Описываются новые производные триазола общей формулы (I) ! ! где значения радикалов приведены в формуле изобретения, фармацевтическая композиция, их содержащая, и способ лечения аутоиммунных заболеваний. Соединения общей формулы (I) и их фармацевтически приемлемые соли обладают эффектом ингибирования связывания S1P и его рецептора Edg-1 (S1P1) и являются пригодными в качестве фармацевтического продукта. 7 н. и 36 з.п. ф-лы, 1 табл.

АНАЛОГИ CYP-ЭЙКОЗАНОИДОВ ДЛЯ ПРИМЕНЕНИЯ В ЛЕЧЕНИИ ИЛИ ПРЕДОТВРАЩЕНИИ НАРУШЕНИЯ, СВЯЗАННОГО С НЕОВАСКУЛЯРИЗАЦИЕЙ И/ИЛИ ВОСПАЛЕНИЕМ

Изобретение относится к применению соединения формулы (I) или его фармацевтически приемлемой соли, которые являются метаболически устойчивыми аналогами биологически активных липидных медиаторов, образующихся из полиненасыщенных жирных кислот омега-3 (ПНЖК n-3), для лечения, снижения риска развития или предотвращения нарушения, связанного с неоваскуляризацией и/или воспалением. Технический результат: лечение, снижение риска развития или предотвращение нарушения, связанного с неоваскуляризацией и/или воспалением. В общей формуле (I) P представляет собой группу, представленную общей формулой (II), E представляет собой группу, представленную общей формулой (III) или (IV), I представляет собой -(CH2)m-Y. Остальные значения переменных указаны в формуле изобретения. 14 з.п. ф-лы, 5 ил., 7 табл., 5 пр. P-E-I (I) -(CH2)n-O-(CH2)k-X (II), ...

ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ АЗОЛОНА, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

Для получения лекарственных средств, предназначенных для лечения связанных с Helicobacter заболеваний, применяют соединения формулы (I), их фармацевтически приемлемые соли с кислотами или их стереохимические изомеры, где Х и У каждый независимо представляет СH или N; R1; R2 и R3 каждый независимо представляет водород или С1-С4-алкил; R4 и R5 каждый независимо представляет водород, галоген, С1-С4-алкил, С1-С4 -алкилоксигруппу, гидроксигруппу, трифторметил, трифторметилоксигруппу или дифторметилоксигруппу; Z - представляет С=О или СНОН и Ar представляет фенил, возможно замещенный вплоть до трех заместителями выбранными из гидроксигруппы, С1-С4-алкила, С1-С4-алкилоксигруппы, галогена, трифторметила, три(С1-С4 -алкил)силилоксигруппы, или пиридинил, замещенный гидроксигруппой и С1-С4-алкилоксигруппой, и (А) представляет радикал формул (а-1), (а-2), (а-3), (а-4), (а-5). Описывается способ их получения, а также фармацевтический препарат, содержащий в качестве активного компонента замещенные производные ...

АНТИФРИКЦИОННЫЙ АГЕНТ НА ОСНОВЕ МЕРКАПТОТРИАЗОЛА ДЛЯ ГАЗОПРОВОДОВ И СПОСОБ ЕГО ПРИГОТОВЛЕНИЯ

Изобретение относится к антифрикционному агенту на основе меркаптотриазола для газопроводов и способу его приготовления. Антифрикционный агент готовят с помощью следующих этапов: получение 1,3-диаминотиомочевины из гидразингидрата и сероуглерода в массовом отношении от 3:1 до 4:1 под действием катализатора I; получение дитиокарбогидразона по реакции конденсации 1,3-диаминотиомочевины и ароматического альдегида в массовом отношении от 1:1 до 1:1,5; получение меркаптотриазольного соединения из дитиокарбогидразона и ароматического сложного эфира в массовом отношении от 1:1 до 1:3 под действием катализатора II; растворение меркаптотриазольного соединения в ацетоне, добавление туда фосфорной кислоты или фосфата(ов) и тщательное перемешивание их с получением целевого продукта. Катализатор I представляет собой 2-хлорэтанол, 2-меркаптоэтанол, этиленхлоргидрин или 2-(2-хлорэтокси)этанол. Катализатор II представляет собой гидроксид калия или гидроксид натрия. Изобретение обеспечивает простые эксплутационные ...

ЦИКЛИЧЕСКИЕ АМИДЫ ИЛИ ИХ СЕЛЬСКОХОЗЯЙСТВЕННО ПРИГОДНЫЕ СОЛИ, ФУНГИЦИДНАЯ КОМПОЗИЦИЯ, СПОСОБ БОРЬБЫ С БОЛЕЗНЯМИ РАСТЕНИЙ, ВЫЗВАННЫМИ ФИТОПАТОГЕННЫМИ ГРИБАМИ

Изобретение относится к циклическим амидам , замещенным в α-положении различными арильными группами, их сельскохозяйственно пригодным солям и составам на их основе, и их использованию в качестве фунгицидов системного или избирательного действия. Указанные соединения представлены общей формулой I (значение радикалов см. в формуле изобретения). 3 с. и 8 з.п.ф-лы, 33 табл.

2-[(4-ГЕТЕРОЦИКЛ-ФЕНОКСИМЕТИЛ)ФЕНОКСИ]-АЛКАНОАТЫ, ГЕРБИЦИДНАЯ КОМПОЗИЦИЯ, СПОСОБ ПОДАВЛЕНИЯ НЕЖЕЛАТЕЛЬНОЙ РАСТИТЕЛЬНОСТИ

Обладающие гербицидной активностью новые 2-(/4-гетероцикл-феноксиметил/фенокси)-алканоаты общей формулы I, приведенной в формуле изобретения, где Q - 4-дифторметил-4,5-дигидро-3-метил-1,2,4-триазол-5/1H/-OH-1-ил, или 1-метил-6-трифторметил-2, 4-/1H, 3H/-пиримидиндион-3-ил; A - группа формулы RO-C(О)-C(R1)H-, где R' - H, CH3, R - H, низший алкил, незамещенный или замещенный хлором, или группа -(CHR7 - CH2 - O)nR8, где R7 - H или метил; R8 - низший алкил; n - 1 или 2; X - H, метил, F или Cl; W - O или S; Z - H, F, Cl, Br, низший алкил или метокси; Z' - H, F или Cl; или Z и Z' - взятые вместе могут представлять собой -(CH2)4 - для образования тетрагидронафтильной группы, используют в создании гербицидной композиции, которую применяют в способе борьбы с нежелательной растительностью. 3 с. и 17 з.п. ф-лы, 5 табл.

СПОСОБЫ И ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ ДЛЯ ПОЛУЧЕНИЯ МЕТИЛАМИДОВ α -МЕТОКСИИМИНОКАРБОНОВЫХ КИСЛОТ

Изобретение относится к способу получения метиламидов α- метоксииминокарбоновых кислот формулы I, где Y означает С-органический радикал, осуществляемому посредством реакции Пиннера взаимодействием ацилцианида формулы II со спиртом и последующим взаимодействием образовавшегося в реакции Пиннера сложного эфира формулы IV а) с гидроксиламином с получением оксима формулы V метилированием оксима формулы V до оксимового эфира формулы VI или б) сометилгидроксиламином с получением оксимового эфира формулы VI, с последующим взаимодействием оксимового эфира формулы VI с метиламином, отличающийся тем, что в реакции Пиннера применяют спирт формулы III R-OH, температура кипения которого выше 75°С. Технический результат - упрощение процесса и получение чистого целевого продукта с высоким выходом. 3 с. и 7 з.п. ф-лы, 23 табл.

АЦИЛЬНЫЕ ПРОИЗВОДНЫЕ АЗОЛОНОВ, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

Описываются новые ацильные производные азолонов общей формулы (1), где значения R1-R6, A, Y, Z указаны в п. 1 формулы изобретения, их фармацевтически приемлемые соли присоединения кислот и стереохимически изомерные формы, которые являются мощными агентами против микроорганизма Helicobacter. Описываются также способ их получения, композиции, включающие указанные соединения, способы их получения и применение этих соединений в качестве лекарственного средства. 4 с. и 4 з.п.ф-лы, 1 табл.

ИНСЕКТИЦИД, АКАРИЦИД И НЕМАТОЦИД, СОДЕРЖАЩИЕ В КАЧЕСТВЕ АКТИВНОГО КОМПОНЕНТА ПРОИЗВОДНОЕ 3-ТРИАЗОЛИЛФЕНИЛСУЛЬФИДА

... 1. Производное 3-триазолилфенилсульфида, представленное формулой [I] где R представляет собой циклопропилметильную группу или трифторэтильную группу; n представляет собой целое число от 0 до 1; A1 И A3 выбирают из групп Группы I и Группы II при условии, что по меньшей мере один из них выбирают из групп Группы II; B2 представляет собой атом водорода, атом галогена или метильную группу и B4 представляет собой атом галогена, цианогруппу, нитрогруппу или C1-C6-алкильную группу (которая может быть моно- или полизамещена атомами галогена) при условии, что, когда A3 представляет собой NH2, B2 представляет собой атом галогена или метильную группу; (Группа I) атом водорода, атом галогена, C1-C6-алкильная группа (которая может быть моно- или полизамещена атомами галогена, гидроксильными группами, цианогруппами, C2-C7-алкоксикарбонильными группами или C1-C6-алкоксигруппами), C3-C8-циклоалкильная группа (которая может быть моно- или полизамещена алкильными группами, атомами галогена, цианогруппами ...

ЭЛАСТОМЕРНЫЕ КОМПОЗИТЫ, СОДЕРЖАЩИЕ МОДИФИЦИРОВАННЫЕ НАПОЛНИТЕЛИ И ФУНКЦИОНАЛИЗИРОВАННЫЕ ЭЛАСТОМЕРЫ

... 1. Эластомерная композиция, включающая, по меньшей мере, один функционализированный эластомер и, по меньшей мере, один модифицированный наполнитель, где модифицированный наполнитель, включает наполнитель, имеющий адсорбированный на нем триазол, включающий:илиили их таутомеры;где Zпредставляет собой алкиленовую группу, где b равняется 0 или 1;X, который является одинаковым или отличающимся друг от друга, представляет собой Н, NH, SH, NHNH, СНО, COOR, СООН, CONR, CN, СН, ОН, NDD' или CF;А является функциональной группой, которая представляет собой SR, SSOH, SONRR', SOSR, SNRR', SNQ, SONQ, CONQ, S-(1,4-пиперазиндиил)-SR, 2-(1,3-дитианил) или 2-(1,3-дитиоланил); или линейный, разветвленный, ароматический или циклический углеводородный радикал, замещенный одной или более из указанных функциональных групп;где R и R', которые являются одинаковыми или отличающимися друг от друга, представляют собой водород; разветвленный или неразветвленный С-Снезамещенный или замещенный алкил, алкенил, алкинил ...

ЗАМЕЩЕННЫЕ N-ФЕНЭТИЛТРИАЗОЛОНАЦЕТАМИДЫ И ИХ ПРИМЕНЕНИЕ

... 1. Соединение формулы (I)в которой Rпредставляет собой (С-С)-алкил, (С-С)-алкенил или (С-С)-алкинил, каждый из которых может быть моно- или дизамещен посредством одинаковых или разных радикалов, выбранных из группы, которая состоит из фтора, хлора, циано, дифторметила, трифторметила, оксо, гидрокси, дифторметокси, трифторметокси, (С-С)-алкокси, (С-С)-циклоалкила и фенила,где (С-С)-циклоалкил может быть замещен до двух раз посредством одинаковых или разных радикалов, выбранных из группы, которая состоит из фтора, трифторметила, (С-С)-алкила, оксо, гидрокси, трифторметокси и (С-С)-алкокси игде фенил может быть замещен до трех раз посредством одинаковых или разных радикалов, выбранных из группы, которая состоит из галогена, циано, дифторметила, трифторметила, (С-С)-алкила, гидрокси, гидроксиметила, дифторметокси, трифторметокси, (С-С)-алкокси, (С-С)-алкоксиметила, гидроксикарбонила, (С-С)-алкоксикарбонила, аминокарбонила, моно-(С-С)-алкиламинокарбонила и ди-(С-С)-алкиламинокарбонила, илипредставляет ...

ИНГИБИТОРЫ 11БЕТА-ГИДРОКСИСТЕРОИДДЕГИДРОГЕНАЗЫ

... 1. Соединение формулы ! R1-CO-X-Y-Z-R2, ! в которой ! Х и Z каждый представляет собой необязательные группы, независимо выбранные из насыщенных или ненасыщенных углеродных цепей, имеющих 1-3 атома углерода в длину, ! Y представляет собой SO, S, SO2, CH=CH, CH2CH2 или О, ! R1 выбран из следующих групп ! ! ! где линия обозначает точку присоединения, ! R2 представляет собой гетероарильную группу, включающую 15 необязательно замещенное 5- или 6-членное кольцо, где кольцо содержит только углерод и по крайней мере один азот, или содержит только углерод и по крайней мере два азота и по крайней мере одну серу, ! и где (i) когда R1 представляет собой , и группа -CO-X-Y-Z-представляет собой CO-CH2-SO, СО-СН2-S или CO-CH2-SO2, то R2 является отличным от , и ! (ii) когда R1 представляет собой, , и группа -CO-X-Y-Z- представляет собой -СО-СН2-О-, то R2 является отличным от . ! 2. Соединение по п.1, где R1 представляет собой . ! 3. Соединение по п.1, где R1 представляет собой . ! 4. Соединение по п.1 ...

АМИД 1,2,4-ТРИАЗОЛ-3-ИЛТИОГЛИКОЛЕВОЙ КИСЛОТЫ, ОБЛАДАЮЩИЙ ПРОТИВОВИРУСНОЙ АКТИВНОСТЬЮ, ИЛИ ЕГО ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ, ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ И ИХ ПРИМЕНЕНИЕ ДЛЯ ЛЕЧЕНИЯ И ПРОФИЛАКТИКИ ГРИППА

... 1. 2-[5-(2-хлор-4-метилфенил)-4-фенил-4H-[1,2,4]тризол-3-илмеркапто]-N-(3,5-диметилфенил)ацетамид, имеющий структурную формулу (I):2. Применение 2-[5-(2-хлор-4-метилфенил)-4-фенил-4H-[1,2,4]тризол-3-илмеркапто]-N-(3,5-диметилфенил)ацетамида, имеющего структурную формулу (I), для профилактики или лечения гриппа.3. Фармацевтическая композиция, содержащая в качестве терапевтически активного агента 2-[5-(2-хлор-4-метилфенил)-4-фенил-4Н-[1,2,4]тризол-3-илмеркапто]-N-(3,5-диметилфенил)ацетамид или его пролекарство.4. Фармацевтическая композиция по п. 2 для профилактики или лечения гриппа.5. Лекарственная форма для профилактики и/или лечения гриппа, полученная на основе фармацевтической композиции по любому из пп. 3-4.6. Лекарственная форма по любому из пп. 3 и 5 в виде таблеток, пластинок, капсул, порошка, свечей, (суппозиториев) или инъекционных растворов.7. Комбинированное лекарственное средство или терапевтический коктейль для профилактики и/или лечения гриппа, полученный на основе фармацевтической ...

ТИОЭФИРНЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ НИТРИФИКАЦИИ

СЛОЖНОЭФИРНОЕ СОЕДИНЕНИЕ И ЕГО ПРИМЕНЕНИЕ

... 1. Сложноэфирное соединение, представленное формулой (1):где Rобозначает C-Cалкил.2. Сложноэфирное соединение по п.1, где относительная конфигурация заместителя по положению 1 циклопропанового кольца и заместителя по положению 3 циклопропанового кольца представляет транс-конфигурацию в формуле (1).3. Сложноэфирное соединение по п.1, где абсолютная конфигурация положения 1 циклопропанового кольца представляет R-конфигурацию в формуле (1).4. Сложноэфирное соединение по п.1, где абсолютная конфигурация положения 1 циклопропанового кольца представляет R-конфигурацию, и относительная конфигурация заместителя по положению 1 циклопропанового кольца и заместителя по положению 3 циклопропанового кольца представляет транс-конфигурацию в формуле (1).5. Сложноэфирное соединение по любому из пп.1-4, где двойная связь заместителя по положению 3 циклопропанового кольца имеет E-конфигурацию или смесь E-конфигурации и Z-конфигурации, и доля конфигурации Е составляет 50% или более в формуле (1).6. Сложноэфирное ...

АМИНОТЕТРАЛИНОВЫЕ ПРОИЗВОДНЫЕ, СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ И ИХ ПРИМЕНЕНИЕ В ТЕРАПИИ

... 1. Аминотетралиновые производные формулы (I)гдеA обозначает 5- или 6-членное кольцо;R обозначает R-W-A-Q-Y-A-X-;Rобозначает водород, C-C-алкил, C-C-циклоалкил-C-C-алкил, галогенированный C-C-алкил, три-(C-C-алкил)-силил-C-C-алкил, гидрокси-C-C-алкил, C-C-алкокси-C-C-алкил, амино-C-C-алкил, C-C-алкиламино-C-C-алкил, ди-C-C-алкиламино-C-C-алкил, C-C-алкилкарбониламино-C-C-алкил, C-C-алкилоксикарбониламино-C-C-алкил, C-C-алкиламинокарбониламино-C-C-алкил, ди-C-C-алкиламинокарбониламино-C-C-алкил, C-C-алкилсульфониламино-C-C-алкил, (необязательно замещенный C-C-арил-C-C-алкил)амино-C-C-алкил, необязательно замещенный C-C-арил-C-C-алкил, необязательно замещенный C-C-гетероциклил-C-C-алкил, C-C-циклоалкил, C-C-алкилкарбонил, C-C-алкоксикарбонил, галогенированный C-C-алкоксикарбонил, C-C-арилоксикарбонил, аминокарбонил, C-C-алкиламинокарбонил, (галогенированный C-C-алкил)аминокарбонил, C-C-ариламинокарбонил, C-C-алкенил, C-C-алкинил, необязательно замещенный C-C-арил, гидрокси, C-C-алкокси, галогенированный ...

СОЕДИНЕНИЯ ДЛЯ ЛЕЧЕНИЯ МЕТАБОЛИЧЕСКИХ ЗАБОЛЕВАНИЙ

... 1. Соединение формулы ! ! где m равно 1; n равно 1 или 2; t равно 0 или 1; и A представляет собой фенил, замещенный 2 группами, выбранными из галогена, алкила, содержащего 1 или 2 атома углерода, перфторметила и перфторметокси. ! 2. Соединение формулы ! ! где m равно 1; n равно 1 или 2; t равно 0 или 1; и A представляет собой фенил, замещенный 2 группами, выбранными из: галогена, алкила, содержащего 1 или 2 атома углерода, перфторметила и перфторметокси.

Способ получения производных 1,2,4-триазолокарбамата

Изобретение относится к способу получения производных 1,2,4-триазоло- карбамата общей формулы сн.

Verfahren zur Herstellung von 1,2,4-Triazolonen-(5)

1,4-Di:phenyl-1,2,4-triazol-5-one cpds. - useful as fungicides, insecticides, acaricides and hypolipaemic agents

Triazole derivs. of formula (I) are new: (Ar1 and Ar2 are phenyl opt. mono- or polysubstd. by alkyl, alkoxy, alkylthio, halogen, NO2, CN, Ph, PhO, haloalkyl, haloalkoxy, haloalkylthio, halophenyl or halophenoxy).

Preparation of triazoline thione derivatives useful as fungicides

High yield preparation of triazoline thione derivatives (I) is carried out by reacting the corresponding hydrazine compound (II) with a thiocyanate, followed by reaction of the resulting thiosemicarbazide with formic acid. Preparation of triazoline thione derivatives of formula (I) comprises: (1) Reacting a hydrazine derivative of formula (II) or a corresponding salt with formaldehyde and a thiocyanate of formula Y-SCN (III) in the presence of a diluent and optionally a catalyst, and (2) Reacting the resulting thiosemicarbazide derivative (IV) with formic acid, optionally in the presence of a catalyst and a diluent. Independent claims are included for the intermediate of formula (IV), which is claimed as new, and for preparation of (II) from a 1-chloro-2-hydroxyethane derivative of formula (V), which is reacted with hydrazine hydrate in the presence of a diluent; (II) is then reacted with (III) without being isolated first. R<1>, R<2> = independently alkyl, alkenyl, cycloalkyl, aralkyl, ...

2-SULFONYLAMINOCARBONYL-2,4-DIHYDRO-3H-1,2,4- TRIAZOL-3-ONE EINSCHLIESSLICH 4,5-KONDENSIERTER, BICYCLISCHER DERIVATE, VERFAHREN UND NEUE ZWISCHENPRODUKTE ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG ALS PFLANZENBEHANDLUNGSMITTEL

Verfahren zur Herstellung von antiphlogistisch wirksamen 3, 5-Dioxo-1, 2, 4-triazolidinen

Insecticide and acaricide 1-di-methyl:carbamoyl-1,2,4-triazole derivs. - prepd. by reaction of a 3-alkylthio-alkylthio-1,2,4-triazole with a di-methyl-carbamoyl halide

New 1,2,4-triazole derivs. are cpds. of formula (Ia) and (Ib). In the formulae, R1 is 1-4C alkyl; R2 is H or CH3; and n is 0 or 1. Also new and claimed are intermediates of formula (II). Cpds. (I) are prepd. by reaction of cpd. (II) with halogen -CO-N(CH3)2 in the presence of base. (Ia, Ib) are pesticides with insecticidal and acaricidal activity, and are useful in plant protection. Some cpds. (Ia, Ib) show activity in tests for systemic activity.

VERFAHREN ZUR HERSTELLUNG (HETERO)AROMATISCHER HYDROXYLAMINE

5-Lipoxygenasehemmende 4-(4-Phenyl-1-piperazinyl)phenole.

Neue Halo-Propargylverbindungen,ihre Verwendung und Verfahren zu ihrer Herstellung.

New heterocyclylalkoxy-substituted benzoyl ketone derivatives are herbicides useful as defoliants, desiccants and especially weedkillers

Heterocyclylalkoxy-substituted benzoyl ketones are new. The heterocyclylalkoxy-substituted benzoyl ketones are compounds of formula (I) and their tautomers and salts: n = 0-2; A = alkanediyl; R<1> = group of formula (a)-(d): m = 0-6; R<5> = halo, or alkyl, alkyl-S- or aryl (each optionally substituted); or two R<5>'s together = alkanediyl; R<6> = OH, OCHO, halo, or alkyl-O-, alkyl-S-, alkyl-SO-, alkyl-SO2-, alkyl-CO-O-, alkyl-O-CO-O-, alkyl-NH-CO-O-, alkyl-SO2-O-, alkenyl-O-, alkynyl-O-, aryl-O-, aryl-S-, aryl-SO-, aryl-SO2-, aryl-CO-O-, aryl-CO-alkyl-O-, aryl-SO2O-, aralkyl-O-, aralkyl-S-, aralkyl-SO- or aralkyl-SO2- (each optionally substituted); R<7> = H; CN; CONH2; CSNH2; halo; or alkyl, alkyl-O-, alkyl-S-, alkyl-SO-, alkyl-SO2-, alkyl-O-CO- or cycloalkyl (each optionally substituted); R<8> = H; or alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl (each optionally substituted); R<9> = OH; OCHO; or alkyl-O-, alkyl-CO-O, alkyl-O-CO-O-, alkyl-NH-CO-O-, alkyl-SO2-O-, ...

Verfahren zur Herstellung von Alkoxytriazolinonen

1.2.4-TRIAZOLIDINE-3.5-DIONE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

DI- UND OLIGO-1,2,4-TRIAZOLIDIN-3,5-DIONE UND VERFAHREN ZU IHRER HERSTELLUNG

AMINOSÄUREDERIVATE, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL UND VERFAHREN ZU IHRER HERSTELLUNG

Mercapto-triazolyl-ketone

New mercapto-triazolyl-ketones have the formula (I), in which R<1>, R<2>, X, Y and m have the meanings given in the description. Also disclosed are their acid addition salts and metal salt complexes, a process for preparing the same and their use as plant-protecting and material-protecting microbicides.

REGIOSELEKTIVE FLUORIERUNG PHENYL-SUBSTITUIERTER TRIAZOLINONE

VERFAHREN ZUR HERSTELLUNG DES HERBIZIDS ALPHA-2-DICHLORO-5-[4-(DIFLUOROMETHYL)-4,5-DIHYDRO-3-METHYL-5-OXO-1H-1,2,4-TRIAZOL-1-YL]-4-FLUOROPHENYLPROPANSÄUREETHYLESTER

Photographisches Material

Verfahren zur Herstellung von substituierten 1,2,4-Triazolen

3-FLUORALKYL-1- ODER -4-SUBSTITUIERTE DELTA HOCH 2 -1,2,4-TRIAZOLIN-4- ODER 1-YLVINYLPHOSPHATE UND DEREN VERWENDUNG

THIONO PHOSPHORIC PHOSPHONIC ACID ESTERS THEIR PREPARATION AND THEIR USE AS INSECTICIDES AND ACARICIDES

... 1437055 Triazolothiazole phosphorus oxyacid esters BAYER AG 8 Oct 1974 [9 Oct 1973] 43522/74 Headings C2P and C2C Novel compounds of the general formula wherein R is C 1 -C 6 alkyl, R1 is C 1 -C 4 alkyl, C 1 -C 6 alkoxy, or phenyl, R11 is amino, monoalkylamino or dialkylamino with 1 to 4 carbon atoms in the or each alkyl portion or is C 1 -C 6 alkoxy, and X is O or S are obtained by reacting (RO)(R1)P(X)Hal wherein Hal is halogen with a compound III the latter being employed in the presence of an acid binding agent or in the form of a salt thereof, e.g. an alkali metal or ammonium salt. The products have insecticidal and acaricidal properties and may be used as active ingredients in conventional pesticidal compositions. The compound is obtained by reacting pyrocarbonic acid diethyl ester with thiosemicarbazide and is reacted with NaOCH 3 in methanol to give the compound The sodium salt of the latter is reacted with chloroacetoacetic acid methyl ester in methanol ...

PESTICIDAL TRIAZOLYL ESTERS OF THIOPHOSPHONIC ACIDS

... 1377203 Pesticidal triazole derivatives containing phosphorus; substituted triazolones AGRIPAT SA 21 Oct 1971 [22 Oct 1970 15 Sept 1971] 49053/71 Headings C2P and C2C [Also in Division A5] Novel compounds of Formula I: where R 1 is alkyl or cycloalkyl having up to 6 carbon atoms or phenyl optionally substituted by one or more Cl and/or Br atoms and one of R 2 and R 3 is -H, C 1-5 alkyl, cycloalkyl having up to 6 carbon atoms or phenyl optionally substituted by one or more Cl atoms while the other of R 2 and R 3 is a radical of formula where R 4 is C 1-5 alkyl or phenyl and R 5 is C 1-5 alkyl may be prepared by reacting a compound of Formula IIa or a metal salt thereof with a compound of formula where Hal is Cl or Br. Hydroxytriazoles (II) and (III) may be made by reacting suitably substituted semicarbazides with alkyl orthocarboxylates. The compounds of Formula I have insecticidal, acaricidal, nematocidal and fungicidal properties and may be used as the active ingredient in conventional ...

HERBICIDAL ARYL TRIAZOLINONES

Novel herbicidal compounds have the formula… …… in which… X is Br, Cl, F alkyl or haloalkyl;… Y is Br, Cl, F, methyl, haloalkyl, nitro, or a radical of the formula R<8>OCH2-, R<8>SCH2-, R<8>SOCH2- or R<8>SO2CH2- where R<8> is C1-3 alkyl, C2-5 alkenyl, C3-5 alkynyl, phenyl, or substituted phenyl;… R<3> is halogen, alkyl, haloalkyl, cyanoalkyl, arylalkyl, alkoxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl or alkylsulfonylalkyl;… R<2> is alkyl, alkoxy, haloalkyl, alkenyl, alkynyl, cyanoalkyl, thiocyanoalkyl, or a group of the formula (C1-5 alkylene)-Y'-R<5>, where Y' is -O-, -S-, -SO- or -SO2- and R<5> is alkyl, alkenyl or alkynyl;… R is dialkylamino, carboxymethyl, hydroxy, haloalkyl, alkyl or aryl;… R<1> is hydrogen, a salt-forming group, alkyl, benzyl, haloalkyl, alkoxy, SO2R, alkynyl, alkenyl, a group of the formula -alkylene-SO2R cyanomethyl, carboxymethyl, alkoxycarbonylmethyl or alkoxymethyl; or R and R<1> together form an alkylene group.

New triazolidines, their manufacture and use

The invention comprises compounds of general formula in which R1 represents a hydrogen or halogen atom or an alky or alkoxy group containing 1 to 4 carbon atoms, and R2 represents a hydroxyl group, a halogen atom, an alkoxy group containing 1 to 4 carbon atoms, a halogeno-alkoxy or hydroxy-alkoxy group containing up to 4 carbon atoms, an unsubstituted phenoxy or benzyloxy group or a phenoxy or benzyloxy group in which the phenyl nucleus is substituted by a halogen atom or by an alkyl or alkoxy group containing up to 4 carbon atoms, or an aliphatic acylamino group containing up to 4 carbon atoms: and their physiologically tolerable salts with an inorganic or organic base: and their preparation by the methods described, these comprising (1) treatment of a reactive functional derivative of a compound of formula or with an alkaline agent, or heating such a compound, (2) reaction of a compound of formula or

PIPERAZINYLALKYLTRIAZOLONES

OLEFINE DERIVATIVES

ANTIFOGGANTS FOR PHOTOGRAPHIC SILVER HALIDE MATERIALS

... 1,274,071. Heterocyclic sulphur compounds. AGFA-GEVAERT A.G. 5 Aug., 1969 [6 Aug., 1968], No. 39066/69. Heading C2C. [Also in Division G2] Compounds are described which are the condensation products of one molecular proportion of phosgene with two molecular proportions of a heterocyclic mercaptan of the triazole, oxazole, thiazole, imidazole, thiadiazole or thiadiazoline series. In examples, phosgene in CCl 4 solution is added to alkaline solutions of 1-phenyl-3- mercapto-1 : 2 : 4-triazole, 2-mercapto-5-anilino-1 : 3 : 4-thiadiazole, 2-mercapto-benzothiazole, 2-mercapto-benzoxazole, 2-mercapto- 4 : 5-di(p-chlorophenyl)-3-phenylimidazole, 2- mercapto-5-thioxo-4-phenyl-1: 3 : 4-thiadiazoline, 2-mercapto-5-butyl-mercapto-1 - 3 - 4-thiadiazole and 2-amino-5-mercapto-1: 3 4-thiadiazole. The condensation products may be heterocyclyl S : S1-diesters of dithiocarbonic acid formed by the phosgene reacting at the mercapto groups, or bis-heterocyclic ketones formed by the phosgene reacting ...

A novel form of amicarbazone, a process for its preparation and use of the same

Compounds

Photographic silver halide emulsions containing fog inhibiting or stabilizing agents

The following heterocyclic mercapto compounds are heated in aqueous solution with sodium chloroacetate to give the corresponding carboxymethylmercapto-derivatives; 1-phenyl-2-imidazole-thione, 2-mercaptopyrimidine and its 4, 6-diamino-, 4, 5, 6-triamino, 4-amino-6-hydroxy or 4-hydroxy-6-methylderivatives, 2-mercaptobenzoxazole, 2-mercaptobenzthiazole, 3-phenyl (or amino)-4-amino-5-mercapto- 1, 2, 4-triazole, 3-mercapto-5-hydroxy (or phenyl) 6-methyl-1, 2, 4-triazine and 2-mercapto-imidazoline and its 4-methyl-derivative. 2-Carboxymethylmercapto- 4, 6-diamino-S-triazine is prepared by adding chloroacetic acid to a solution of 4, 6-diamino-2-mercapto-s-triazine in aqueous sodium hydroxide. 2-(1-Carboxyoctylmercapto)-4, 6-diamino-S-triazine is prepared by stirring a solution of a -bromopelargonic acid and 4, 6-diamino-2-mercapto-s-triazine in aqueous sodium hydroxide. 2-Carboxymethylmercapto-imidazoline chloroacetate is prepared by p boiling 2-mercapto-imidazoline and chloroacetic acid in ...

Herbicidal acetanilide derivatives

Compounds of the formula wherein Ar is aryl, R1 is halomethyl, R2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, haloalkyl, alkylthio, alkenylthio, alkynylthio, aryl or NR5R6 wherein R5 and R6 individually are hydrogen, alkyl, alkenyl or alkynyl, R3 is hydrogen or alkyl, n is 1 or 2, Y is O, S or NR wherein R is hydrogen, alkyl, alkenyl or alkynyl, have been found to be useful herbicides.

CEPHALOSPORIN COMPOUNDS

1-ACYL-4-(O-HALOPHENYL)THIOSEMICARBAZIDES

... 1506022 1 - Acyl - 4(o - halophenyl) thiosemicarbazides ELI LILLY & CO 6 March 1975 [7 March 1974] 44476/77 Divided out of 1506021 Heading C2C The invention comprises 1-acyl-4-(o-halophenyl)-3-thiosemicarbazides of the general Formula I wherein R is hydrogen, C 1 to C 11 alkyl, cyclopropyl or trifluoromethyl; R 1 is hydrogen, bromo, chloro or fluoro; R 2 and R 3 are independently hydrogen, C 1 to C 3 alkyl, C 1 to C 3 alkoxy, bromo, chloro, fluoro or trifluoromethyl provided that at least one of R 2 and R 3 is hydrogen; X is bromo, chloro or fluoro and provided that when R 1 is hydrogen, R is other than hydrogen and R 2 is hydrogen. The compounds of Formula I may be prepared by molar equivalents of an acyl hydrazine of formula NH 2 NHCOR and an o-halophenylisothiocyanate in a substantially anhydrous aprotic solvent at from 60‹ to 100‹ C. for about 24 hours.

Triazolone compounds as mPGES-1 inhibitors

Imadazole fungicides.

Compounds of formula ...

Substituted azolone derivatives.

The use of the manufacture of a madicament for treating ...

IMIDAZOLE FUNGICIDES

1-heterocycle substituted diarylamines.

... 1-heterocycle substituted diarylamines, methods of making and using them, and compositions containing them.

Substituted azolone derivatives

Substituted heteroaryl-and phenyl-sulfamoyl compounds

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

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

Benzamide and heteroarylamide as P2X7 receptor antagonists

The present invention relates to novel to P2X7 inhibitors of' formula (I) and to processes for their preparation, intermediates useful in their preparation, pharmaceutical compositions containing them, and their use in therapy. The active compounds of the present invention are potent inhihitors of P2X7 and as such are useful in the treatmentof inflammation, osteoarthrits, rheumatoid arthritis, cancer, reperfusion ischemia in stroke or heart attack, autoimmune diseases and other disorders.

Triazolone compounds as mPGES-1 inhibitors

Anilides of acids thioglicolic carrying heterocyclic substances, which have fungicidal properties usable in phytiatrie.

New 0-triazololyl-thionophosphoric esters and esteramides of acids (phosphonic), their method of preparation and their application like insecticide and acaricides.

Esters triazolylic of acids of phosphorus and products pesticides which contain some.

Useful diesters of acids N-sulfonyl-immino-thiocarbonic as antagonists of weedkillers for the crop protection of rice.

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

1-Heterocycle substituted diarylamines.

Esters triazolylic of acids oxygenated of phosphorus and products pesticides which contain some.

Herbicidal compositions containing triazolinones

Derived from cephalosporine.

Herbicidal triazolinones.

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

Heterocyclic herbicides.

New triazolidines carrying of the basic substituents and their method of preparation.

New phosphoric esters 1,2,4-triazole and their preparation.

Imidazole fungicides.

Benzamide and heteroarylamide as P2X7 receptor antagonists.

Fungicidal and growth regulant compounds.

Benzamide and heteroarylamide as p2x7 receptor antagonist.

Triazolone compounds as mPGES-1 inhibitors

Substituted heteroaryl-and phenyl-sulfamoyl compounds

IMIDAZOLE FUNGICIDES

Substituted azolone derivatives

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

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

Substituted heteroaryl-and phenyl-sulfamoyl compounds

RETINOIDE FOR THE TREATMENT OF EMPHYSEM

DIAMINE UND BISMALEINIMIDE, SOWIE DARAUS HERGESTELLTE POLYIMIDE

PCT No. PCT/EP89/00120 Sec. 371 Date Aug. 22, 1990 Sec. 102(e) Date Aug. 22, 1990 PCT Filed Feb. 9, 1989 PCT Pub. No. WO89/08107 PCT Pub. Date Sep. 8, 1989.A diamine or bismaleimide of the general formula I I in which R1 and R2 denote an H atom or together denote the group -OC-CH=CH-CO-, Y1 and Y2 independently of one another deonte O or S and Het denotes a thiazole, a thiadiazole or a 1-methyltriazole ring. The diamines and bismaleimides are used for the preparation of polyimides which are if appropriate reinforced with fibers and if appropriate incompletely hardened.

COLORPHOTOGRAPHIC MATERIAL

VERFAHREN ZUR HERSTELLUNG DES NEUEN 1-(3-(4-M-CHLORPHENYL-1-PIPERAZINYL)-PROPYL)-3,4-DIATHYL-DELTA2-1,2,4-TRIAZOLIN-5-ON UND DESSEN PHARMAKOLOGISCH VERWENDBAREN SALZEN

Compounds and Methods for Treating Cancer and Diseases of the Central Nervous System

Disclosed are compounds of the general formula (I): compositions comprising an effective amount of said compounds either alone or in combination with other chemotherapeutic agents, and methods useful for treating or preventing cancer and for inhibiting tumour tissue growth. These compounds attenuate the oxidative damage associated with increased heme-oxygenase activity and can reduce cell proliferation in transformed cells. In addition, the described compounds and compositions are useful as neuroprotectants and for treating or preventing neurodegenerative disorders and other diseases of the central nervous system.

Antifungal 1,2,4-triazolyl Derivatives

The present invention relates to novel triazole compounds of the formulae I and II as defined below which carry a sulfur substituent, to agricultural compositions containing them, to their use as fungicides and to intermediate compounds used in the method of producing them.

Five-membered heterocycles useful as serine protease inhibitors

The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R 3 , R 4 , R 6 , R 11 , X 1 , X 2 , and X 3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

Antifungal 1,2,4-triazolyl Derivatives

The present invention relates to novel triazole compounds of the formulae I and II as defined below which carry a sulfur substituent, to agricultural compositions containing them, to their use as fungicides and to intermediate compounds used in the method of producing them.

Compound inhibiting in vivo phosphorus transport and medicine containing the same

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

Compounds, Compositions and Methods of Using Same for Modulating Uric Acid Levels

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

TRIAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY

The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound. 167-. (canceled)73. The compound of wherein R claim 72 , Rand Rare each independently —OH claim 72 , —SH claim 72 , —NHR claim 72 , —OC(O)NRR claim 72 , —SC(O)NRR claim 72 , —OC(O)R claim 72 , —SC(O)R claim 72 , —OC(O)OR claim 72 , —SC(O)OR claim 72 , —OS(O)R claim 72 , —S(O)OR claim 72 , —SS(O)R claim 72 , —OS(O)OR claim 72 , —SS(O)OR claim 72 , —OC(S)R claim 72 , —SC(S)R claim 72 , —OC(S)OR claim 72 , —SC(S)OR claim 72 , —OC(S)NRR claim 72 , —SC(S)NRR claim 72 , —OC(NR)R claim 72 , —SC(NR)R claim 72 , —OC(NR)OR claim 72 , —SC(NR)OR claim 72 , —OP(O)(OR)or —SP(O)(OR).74. A pharmaceutical composition claim 68 , comprising a pharmaceutically acceptable carrier and a compound of .75. The pharmaceutical composition of claim 74 , further comprising one or more additional therapeutic agents.76. A method of treating cancer in a mammal claim 68 , comprising administering to the mammal an effective amount of a compound of any one of .77. A method of treating cancer in a mammal claim 69 , comprising administering to the mammal an effective amount of a compound of any one of .78. A method of treating cancer in a mammal claim 70 , comprising administering to the mammal an effective amount of a compound of any one of .79. A method of treating cancer in a mammal claim 71 , comprising administering to the mammal an effective amount of a compound of any one of .80. A method of treating cancer in a mammal claim 72 , comprising administering to the mammal an effective amount of a compound of any one of .81. A ...

ESTER COMPOUND AND USE THEREOF

An ester compound represented by formula (1): wherein Rrepresents hydrogen or methyl, Rrepresents hydrogen or C1-C4 alkyl, and Rrepresents hydrogen or C1-C4 alkyl; has an excellent pest control effect and is therefore useful as an active ingredient of a pest control agent. 2. The ester compound according to claim 1 , wherein a relative configuration of the substituent at the 1-position of the cyclopropane ring and the substituent at the 3-position of the cyclopropane ring is a trans configuration in formula (1).3. The ester compound according to claim 1 , wherein an absolute configuration of the 1-position of the cyclopropane ring is an R configuration in formula (1).4. The ester compound according to claim 1 , wherein an absolute configuration of the 1-position of the cyclopropane ring is an R configuration claim 1 , and a relative configuration of the substituent at the 1-position of the cyclopropane ring and the substituent at the 3-position of the cyclopropane ring is a trans configuration in formula (1).5. The ester compound according to claim 1 , wherein a relative configuration of the substituent of the 1′-position existing on the substituent at the 3-position of the cyclopropane ring is Z-configuration in formula (1).6. The ester compound according to claim 1 , wherein an absolute configuration of the 1-position of the cyclopropane ring is an R configuration and a relative configuration of the substituent of the 1′-position existing on the substituent at the 3-position of the cyclopropane ring is Z-configuration in formula (1).7. The ester compound according to claim 1 , wherein an absolute configuration of the 1-position of the cyclopropane ring is an R configuration claim 1 , a relative configuration of the substituent at the 1-position of the cyclopropane ring and the substituent at the 3-position of the cyclopropane ring is a trans configuration claim 1 , and a relative configuration of the substituent of the 1′-position existing on the substituent at ...

Hepatitis C Virus Inhibitors

The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS5A protein. 13. A compound , or a stereoisomer or a pharmaceutically acceptable salt thereof , selected from the group consisting of:(4,5-bis(4-(((2S)-2-(((benzyloxy)carbonyl)amino)propanoyl)amino)phenyl)-1,3-oxazol-2-yl)acetic acid;ethyl (4,5-bis(4-(((2S)-2-(((benzyloxy)carbonyl)amino)propanoyl)amino)phenyl)-1,3-oxazol-2-yl)acetate;dibenzyl((2-methyl-1,3-oxazole-4,5-diyl)bis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))biscarbamate;dibenzyl (1H-imidazole-4,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))biscarbamate;(2S,2′S)—N,N′-(1H-imidazole-4,5-diyldi-4,1-phenylene)bis(2-((phenylacetyl)amino)propanamide);dibenzyl((5-oxo-1,5-dihydro-4H-1,2,4-triazole-3,4-diyl)bis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))biscarbamate;dibenzyl (4H-1,2,4-triazole-3,4-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))biscarbamate;dibenzyl (1H-1,2,3-triazole-4,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))biscarbamate;(2S,2′S)—N,N′-(1H-pyrazole-3,5-diyldi-4,1-phenylene)bis(2-(((2S)-2-hydroxy-2-phenylacetyl)amino)propanamide);(2S,2′S)—N,N′-(1H-pyrazole-3,5-diyldi-4,1-phenylene)bis(2-(((2R)-2-hydroxy-2-phenylacetyl)amino)propanamide);(2S,2′S)—N,N′-(1H-pyrazole-3,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))bis(2-hydroxy-2-phenylpropanamide);(2R,2′R)—N,N′-(1H-pyrazole-3,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))bis(2-hydroxy-2-phenylpropanamide);N,N′-(1H-pyrazole-3,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))bis(3-chloro-1-naphthamide);N,N′-(1H-pyrazole-3,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))bis(3-chloro-1-isoquinolinecarboxamide);(2S,2′S)—N,N′-(1,3-oxazole-2,5-diyldi-4,1-phenylene)bis(2-(((2S)-2-hydroxy ...

Novel HSP90 Inhibitor

Disclosed is a triazole derivative(s) represented by the general formula (1) below or a pharmacologically acceptable salt(s) thereof. Also disclosed are a prodrug(s) of such a triazole derivative(s) and an HSP90 inhibitor(s) containing any one of them as an active constituent. (1) (In the formula, X represents a halogen atom, an optionally substituted alkyl group, an optionally substituted alkynyl group or the like; Y represents a mercapto group, a hydroxyl group, an optionally substituted sulfonyl group, an optionally substituted amino group or the like; and R represents an optionally substituted aryl or alkyl group or the like.) 2. The method according to claim 1 , wherein X is located at the 5 position of 2 claim 1 ,4-dihydroxyphenyl group which binds to the triazole ring at 1 position in said general formula (1) claim 1 , or a pharmaceutically acceptable salt thereof.3. The method according to or claim 1 , wherein X is an optionally substituted alkyl group claim 1 , an optionally substituted alkenyl group or an optionally substituted alkynyl group claim 1 , or a halogen atom in said general formula (1) claim 1 , or a pharmaceutically acceptable salt thereof.4. The method according to claim 1 , wherein Y is any of a mercapto group claim 1 , hydroxy group claim 1 , an optionally substituted sulfonyl group or alkylthio group in said general formula (1) claim 1 , or a pharmaceutically acceptable salt thereof.5. The method according to claim 1 , wherein Y is a hydroxy group in said general formula (1) claim 1 , or a pharmaceutically acceptable salt thereof.6. The method according to claim 1 , wherein m is 0 or 1 claim 1 , and A is a cyclic amino group in the general formula (2) claim 1 , or a pharmaceutically acceptable salt thereof.8. The method according to claim 1 , wherein said triazole derivative is selected from the group consisting of:4-isopropyl-6-{5-mercapto-4-[4-(morpholin-4-yl)-phenyl]-4H-[1,2,4]triazol-3-yl}-benzene-1,3-diol (SH-a01),4-isopropyl-6-{5- ...

Novel HSP90 Inhibitor

Disclosed is a triazole derivative(s) represented by the general formula (1) below or a pharmacologically acceptable salt(s) thereof. Also disclosed are a prodrug(s) of such a triazole derivative(s) and an HSP90 inhibitor(s) containing any one of them as an active constituent. (1) (In the formula, X represents a halogen atom, an optionally substituted alkyl group, an optionally substituted alkynyl group or the like; Y represents a mercapto group, a hydroxyl group, an optionally substituted sulfonyl group, an optionally substituted amino group or the like; and R represents an optionally substituted aryl or alkyl group or the like.)

Novel HSP90 Inhibitor

Disclosed is a triazole derivative(s) represented by the general formula (1) below or a pharmacologically acceptable salt(s) thereof. Also disclosed are a prodrug(s) of such a triazole derivative(s) and an HSP90 inhibitor(s) containing any one of them as an active constituent. (1) (In the formula, X represents a halogen atom, an optionally substituted alkyl group, an optionally substituted alkynyl group or the like; Y represents a mercapto group, a hydroxyl group, an optionally substituted sulfonyl group, an optionally substituted amino group or the like; and R represents an optionally substituted aryl or alkyl group or the like.) 2. The method of claim 1 , wherein the compound is not3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-trifluoromethyl-phenyl)-5-carbamoyloxy-[1,2,4]triazole;3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-methyl-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole;3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(8-methoxy-quinolin-5-yl)-5-carbamoyloxy-[1,2,4]triazole;3-(2-Hydroxy-4-ethoxycarbonyoxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-hydroxy-[1,2,4]triazole;3-(2-Hydroxy-4-ethoxycarbonyoxy-5-ethyl-phenyl)-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-chloro-phenyl]-4-(quinolin-5-yl)-5-mercapto-[1,2,4]triazole;3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(2,3-difluoro-phenyl)-5-mercapto-[1,2,4]triazole; or3-[2-Hydroxy-4-isobutyryloxy-5-ethyl-phenyl]-4-(1-methyl-benzo-imidazol-4-yl)-5-hydroxy-[1,2,4]triazole.3. The method of claim 1 , wherein when Y is —OH or —SH claim 1 , Rand Rare selected from the group consisting of an acyl group claim 1 , a carbamoyl group claim 1 , an alkoxycarbonyl group claim 1 , and an alkoxymethyl group.4. The method of claim 1 , wherein Rand Rare the same.5. The method of claim 1 , wherein R is an optionally substituted carbocyclic aryl group.6. The method of claim 1 , wherein R is an ...

Cyclic n,n'-diarylthioureas and n,n'-diarylureas - androgen receptor antagonists, anticancer agent, method for preparation and use thereof

The present invention relates to novel cyclic N,N′-diarylureas and N,N′-diarylthioureas—androgen receptor antagonists, anti-cancer agent, pharmaceutical composition, medicament, and method for treatment of cancerous diseases, among them prostate cancer. Cyclic N,N′-diarylthioureas or N,N′-diarylureas of the general formula 1, their optical (R)- and (S)-isomers and pharmaceutically acceptable salts thereof exhibiting properties of androgen receptor antagonists have been proposed, wherein: X represents oxygen or sulfur; m=0 or 1; R1 represents C 1 -C 3 alkyl; R2 and R3 represent hydrogen; or R2 and R3 together with C-atom they are attached to form C═O group; R4 and R5 represent hydrogen; or R4 represents hydrogen, R5 represents methyl; or R4 represents methyl, R5 represents CH 2 R6 group in which R6 represents C 1 -C 3 alkoxycarbonyl, carboxyl, hydroxyl group optionally substituted with methyl or benzyl; or R4 and R5 together with C-atom they are attached to form 5- or 6-membered heterocycle comprising at least one oxygen atom or nitrogen atom optionally substituted with methyl; or R4 and R5 together with C-atom they are attached to form NH group.

Novel HSP90 Inhibitor

Disclosed is a triazole derivative(s) represented by the general formula (1) below or a pharmacologically acceptable salt(s) thereof. Also disclosed are a prodrug(s) of such a triazole derivative(s) and an HSP90 inhibitor(s) containing any one of them as an active constituent. (1) (In the formula, X represents a halogen atom, an optionally substituted alkyl group, an optionally substituted alkynyl group or the like; Y represents a mercapto group, a hydroxyl group, an optionally substituted sulfonyl group, an optionally substituted amino group or the like; and R represents an optionally substituted aryl or alkyl group or the like.) 1. A triazole derivative represented by the following general formula (6) or a pharmaceutically acceptable salt thereof, This application is a continuation of U.S. Ser. No. 11/885,575, filed Sep. 4, 2007, which is a §371 of PCT/JP2006/304496 filed Mar. 8, 2006, the disclosures of which are hereby incorporated by reference.The present invention relates to a novel triazole derivative and an HSP90 inhibitor containing the triazole derivative as an active ingredient. The triazole derivative of the present invention inhibits the function of HSP90 by binding to its ATP binding site, blocks the binding of HSP90 and its client protein and finally suppresses cellular growth.Molecular chaperones are a general term for proteins that form a complex temporally with client proteins to promote the formation of the conformation of the client proteins. These proteins, the activity of which is to help folding and association of protein and to prevent aggregation, are broadly defined as molecular chaperones and classified into several families according to their molecular weights (HSP90, HSP70, HSP60, HSP40, small HSPs and the like). In particular, HSP90 has been known to interact with many molecules which are involved in the intracellular signal transduction, and it is becoming clear that HSP90 is deeply involved in cell cycle regulation, and carcinogenesis ...

Bisaryl-bonded aryltriazolones and use thereof

The present application relates to novel bisaryl-linked 5-aryl-1,2,4-triazolone derivatives, to processes for preparing them, to their use alone or in combinations for the treatment and/or prevention of diseases and also to their use for the production of medicaments for the treatment and/or prevention of diseases, more particularly for the treatment and/or prevention of cardiovascular disorders.

1, 2, 4-TRIAZOLONE DERIVATIVE

The present invention provides a 1,2,4-triazolone derivative represented by Formula (1A) having an antagonistic activity on the arginine-vasopressin 1b receptor or a pharmaceutically acceptable salt thereof and provides a pharmaceutical composition comprising the compound or the salt as an active ingredient, in particular, a therapeutic or preventive agent exhibiting favorable pharmacokinetics in a disease such as mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastrointestinal disease, drug addiction, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, head injury, inflammation, immune-related disease, or alopecia. 4. The 1 claim 1 ,2 claim 1 ,4-triazolone derivative or pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sup': '1', 'sub': '1-5', 'Ris a Calkyl;'}{'sup': '2', 'Ris a hydrogen atom; and'}{'sup': '3', 'sub': 1-5', '1-5, 'Ris phenyl or pyridyl (the phenyl or pyridyl is optionally substituted by one or two groups selected from the group consisting of Calkyl, Calkoxy, halogen atoms, cyano, hydroxy, trifluoromethyl, difluoromethoxy, and trifluoromethoxy).'}5. The 1 claim 1 ,2 claim 1 ,4-triazolone derivative or pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sub': '1-5', 'A is phenylene, pyridinediyl, or pyrimidinediyl (the phenylene, pyridinediyl, and pyrimidinediyl are optionally substituted by one or two groups selected from halogen atoms and Calkoxy).'}6. The 1 claim 1 ,2 claim 1 ,4-triazolone derivative or pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sub': '1-5', 'A is phenylene or pyridinediyl (the phenylene and pyridinediyl are optionally substituted by one or two groups selected from halogen atoms and Calkoxy).'}8. The 1 claim 1 ,2 claim 1 ,4-triazolone derivative or pharmaceutically acceptable salt thereof according to claim 1 , whereinX is a single bond;n is an integer ...

SUBSTITUTED N-PHENETHYLTRIAZOLONEACETAMIDES AND USE THEREOF

The present application relates to novel substituted N-phenethyltriazoloneacetamides, to processes for preparing them, to their use alone or in combinations for the treatment and/or prevention of diseases and also to their use for the production of medicaments for the treatment and/or prevention of diseases, more particularly for the treatment and/or prevention of cardiovascular disorders. 5. (canceled)6. A method of treatment and/or prevention of acute and chronic heart failure claim 1 , hypervolaemic and euvolaemic hyponatraemia claim 1 , cirrhosis of the liver claim 1 , ascites claim 1 , oedema and the syndrome of inadequate ADH secretion (SIADH) comprising administering a compound of to a patient in need thereof.7. (canceled)8. A pharmaceutical composition comprising a compound of and one or more inert non-toxic pharmaceutically suitable auxiliaries.9. The pharmaceutical composition comprising a compound of and at least one active substance selected from the group consisting of a diuretic claim 1 , an angiotensin AII antagonist claim 1 , an ACE inhibitor claim 1 , a beta-receptor blocker claim 1 , a mineralocorticoid receptor antagonist claim 1 , an organic nitrate claim 1 , an NO donor and a positive-inotropic active substance.10. A method of treatment and/or prevention of acute and chronic heart failure claim 8 , hypervolaemic and euvolaemic hyponatraemia claim 8 , cirrhosis of the liver claim 8 , ascites claim 8 , oedema and the syndrome of inadequate ADH secretion (SIADH) comprising administering the pharmaceutical composition of to a patient in need thereof. The present application relates to novel substituted N-phenethyltriazoloneacetamides, to processes for preparing them, to their use alone or in combinations for the treatment and/or prevention of diseases and also to their use for the production of medicaments for the treatment and/or prevention of diseases, more particularly for the treatment and/or prevention of cardiovascular disorders.The liquid ...

Substituted phenylacetate and phenylpropane amides and use thereof

The present application relates to novel substituted phenylacetamides and phenylpropanamides, to processes for preparing them, to their use alone or in combinations for the treatment and/or prevention of diseases and also to their use for the production of medicaments for the treatment and/or prevention of diseases, more particularly for the treatment and/or prevention of cardiovascular disorders.

4-SUBSTITUTED-3-BENZYLOXY-BICYCLO[3.1.0]HEXANE COMPOUNDS AS mGluR 2/3 ANTAGONISTS

A mGlu2/3 receptor antagonist of the formula: its uses, and methods for its preparation are described.

COMPOSITIONS AND METHODS FOR QUADRICYCLANE MODIFICATION OF BIOMOLECULES

The present disclosure features a strain-promoted [2+2+2] reaction that can be carried out under physiological conditions. In general, the reaction involves reacting a pi-electrophile with a low lying LUMO with a quadricyclane on a biomolecule, generating a covalently modified biomolecule. The selectivity of the reaction and its compatibility with aqueous environments provides for its application in vivo and in vitro. The reaction is compatible with modification of living cells. In certain embodiments, the pi-electrophile can comprise a molecule of interest that is desired for delivery to a quadricyclane-containing biomolecule via [2+2+2] reaction. 43. The compound of any of - claims 1 , wherein M is selected from one of the following: nickel (II) claims 1 , palladium (II) claims 1 , platinum (II) claims 1 , cobalt (I) claims 1 , iridium (I) claims 1 , rhodium (I) claims 1 , copper (II) claims 1 , copper (III) claims 1 , silver (III) claims 1 , gold (III) claims 1 , tungsten claims 1 , and iron.53. The compound of any of - claims 1 , wherein nickel (II) claims 1 , palladium (II) claims 1 , and platinum (II).63. The compound of any of - claims 1 , wherein Ar claims 1 , Ar claims 1 , Ar claims 1 , and Arare optional and are aryl claims 1 , substituted aryl claims 1 , heteroaryl claims 1 , or substituted heteroaryl groups.73. The compound of any of - claims 1 , wherein Ar claims 1 , Ar claims 1 , Ar claims 1 , or Aris aryl or substituted aryl.83. The compound of any of - claims 1 , wherein R claims 1 , R claims 1 , R claims 1 , or Ris hydrogen.93. The compound of any of - claims 1 , wherein R claims 1 , R claims 1 , R claims 1 , or Ris alkylene claims 1 , substituted alkylene claims 1 , alkenylene claims 1 , substituted alkenylene claims 1 , alkynylene claims 1 , or substituted alkynylene.103. The compound of any of - claims 1 , wherein Y claims 1 , Y claims 1 , Y claims 1 , or Yis hydrogen or halogen.113. The compound of any of - claims 1 , wherein Y claims 1 , Y ...

Compounds for the treatment of metabolic disorders

Compounds useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis, are disclosed.

TGR5 AGONISTS

TGR5 agonists of structural formula VIII(Q), wherein X, R, R, and Rare defined in the specification, pharmaceutically acceptable salts thereof, compositions thereof, and use of the compounds and compositions for treating diseases. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases. 4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '4', 'X is ═C(R)—;'}{'sub': 2', '3', '2', '3', '3', '2', '2', '2', '2', '2', '2', '1', '3', '1', '3, 'sup': Y', 'Y', 'Y', 'Y, 'Y is a bond, —S—, —S(O)—, —CH(CH)—S(O)—, —CH(CH)—S—, —CH(OH)—, —CH(CH)—O—, —C(O)—, —(CH)—S—, —CH—N(R)—, —CH(halo)-, —CH—S(O)—, —S(O)—N(R)—, —(CH)—O—, or —C(O)—N(R)—, wherein Ris H, —(C-C)alkyl or hydroxyl(C-C)alkyl;'}{'sub': 3', '2, 'each R is independently selected from H, —CH, —OH, F and —CHOH;'}{'sup': D1', 'D1', 'D10', 'D10, 'sub': 3', '6, 'Ris selected from phenyl, —N(H)-phenyl, —(C-C)cycloalkyl, -(5-6 membered)heterocycloalkyl, -(5-6 membered)heteroaryl-(5-6 membered)heterocycloalkyl, -(5-6 membered)heteroaryl, wherein Ris substituted with 1, 2, or 3 R, wherein the 1-3 Rgroups are 0-2 A groups and 1 B group;'}{'sub': 3', '2', '1', '4', '1', '4, 'each A group, when they occur, is independently selected from halo, —CF, —CN, —NO, —OH, —O—(C-C)alkyl optionally substituted with 1-3 substituents independently selected from —OH and halo, and —(C-C)alkyl optionally substituted with 1-3 substituents independently selected from —OH and halo;'}{'sub': 1', '4', '1', '4', '1', '4', '2', '1', '4', '2', '2', '2', '1', '4', '2', '1', '4', '2', '2', '1', '4', '1', '6', '1', '4', '2', '2', '0', '4', '2', '0', '4', '1', '4', '1', '3', '1', '3', '1', '6', '0', '3, 'sup': D11', 'D11B', 'D11D', 'D11', 'A', 'A', 'D11', 'D11B', 'D11', 'D11', 'D11D', 'R', 'A', 'D11D', 'A', 'D', 'A', 'D11D', 'D11', 'A', 'D11D', 'A', 'D11B', 'D11D', 'D11', 'A', 'A', 'DllF', 'D11D', 'D11', 'D11D', 'D11', 'D11', 'D11, ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula X: 7. The compound of claim 6 , where Ris H and Ris —CHCH.21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .22. The pharmaceutical composition of claim 21 , further comprising a therapeutic agent selected from adenosine receptor antagonists claim 21 , α-adrenergic receptor antagonists claim 21 , β-adrenergic receptor antagonists claim 21 , β-adrenergic receptor agonists claim 21 , dual-acting β-adrenergic receptor antagonist/α-receptor antagonists claim 21 , advanced glycation end product breakers claim 21 , aldosterone antagonists claim 21 , aldosterone synthase inhibitors claim 21 , aminopeptidase N inhibitors claim 21 , androgens claim 21 , angiotensin-converting enzyme inhibitors and dual-acting angiotensin-converting enzyme/neprilysin inhibitors claim 21 , angiotensin-converting enzyme 2 activators and stimulators claim 21 , angiotensin-II vaccines claim 21 , anticoagulants claim 21 , anti-diabetic agents claim 21 , antidiarrheal agents claim 21 , anti-glaucoma agents claim 21 , anti-lipid agents claim 21 , antinociceptive agents claim 21 , anti-thrombotic agents claim 21 , ATreceptor antagonists and dual-acting ATreceptor antagonist/neprilysin inhibitors and multifunctional angiotensin receptor blockers claim 21 , bradykinin receptor antagonists claim 21 , calcium channel blockers claim 21 , chymase inhibitors claim 21 , digoxin claim 21 , diuretics claim 21 , dopamine agonists claim 21 , endothelin converting enzyme inhibitors claim 21 , endothelin receptor antagonists claim 21 , HMG-CoA reductase inhibitors claim 21 , estrogens claim 21 , estrogen receptor agonists and/or antagonists claim 21 , monoamine reuptake inhibitors claim 21 , muscle relaxants claim 21 , natriuretic peptides and their analogs claim 21 , natriuretic peptide clearance receptor antagonists claim 21 , neprilysin inhibitors claim 21 , nitric oxide donors claim 21 , non ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula XII: 3. The compound of claim 2 , where Ris H and Ris selected from H and —CHCH.5. The compound of claim 4 , where Ris H and Ris selected from H and —CHCH.13. The compound of claim 12 , where Ris H and Ris selected from H claim 12 , —CHOC(O)CH claim 12 , —CHOC(O)OCHCH claim 12 , —CHOC(O)OCH(CH) claim 12 , and —C(O)CH[CH(CH)]—NHC(O)OCH.15. The compound of claim 14 , where R is —CH claim 14 , Ris H claim 14 , and Ris selected from —CHOC(O)CH claim 14 , —CHOC(O)OCH(CH) claim 14 , —CHOC(O)OCHCH claim 14 , and —CHOC(O)CH[CH(CH)]—NHC(O)OCH.19. The compound of claim 18 , where Ris H and Ris selected from —CHOC(O)OCHCHand —CHOC(O)CH[CH(CH)]—NHC(O)OCH.21. The compound of claim 20 , where Ris H claim 20 , Ris —CHOP(O)(OH)or —CHOC(O)CH[CH(CH)]NH claim 20 , and Ris —CHCH; or Ris —C(O)CH[CH(CH)]NH claim 20 , Ris H claim 20 , and Ris —CHCH.23. The compound of claim 22 , where R claim 22 , R claim 22 , and Rare H; or Rand Rare H claim 22 , and Ris —CHOC(O)OCHCH.25. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .26. The pharmaceutical composition of claim 25 , further comprising a therapeutic agent selected from adenosine receptor antagonists claim 25 , α-adrenergic receptor antagonists claim 25 , β-adrenergic receptor antagonists claim 25 , β-adrenergic receptor agonists claim 25 , dual-acting β-adrenergic receptor antagonist/α-receptor antagonists claim 25 , advanced glycation end product breakers claim 25 , aldosterone antagonists claim 25 , aldosterone synthase inhibitors claim 25 , aminopeptidase N inhibitors claim 25 , androgens claim 25 , angiotensin-converting enzyme inhibitors and dual-acting angiotensin-converting enzyme/neprilysin inhibitors claim 25 , angiotensin-converting enzyme 2 activators and stimulators claim 25 , angiotensin-II vaccines claim 25 , anticoagulants claim 25 , anti-diabetic agents claim 25 , antidiarrheal agents claim 25 , anti- ...

POLYMORPHIC FORMS OF 2-(5-BROMO-4-(4-CYCLOPROPYLNAPHTHALEN-1-YL)-4H-1,2,4-TRIAZOL-3-YLTHIO)ACETIC ACID AND USES THEREOF

Crystalline polymorph forms of 2-(5-bromo-4-(4-cyclopropyl naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid are described. Pharmaceutical compositions and the uses of such compounds, compound forms, and compositions for the treatment of a variety of diseases and conditions are also presented. 2. The method of claim 1 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08° 2θ±0.1° 2θ.3. The method of claim 1 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in .4. The method of claim 1 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate.5. The method of claim 1 , further comprising administering allopurinol.6. The method of claim 1 , further comprising administering febuxostat.8. The method of claim 7 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08° 2θ±0.1° 2θ.9. The method of claim 7 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in .10. The method of claim 7 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 7 ,2 claim 7 ,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate.11. The method of claim 7 , further comprising administering allopurinol.12. The method of claim 7 , further comprising administering febuxostat.14. The method of claim 13 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08° 2θ±0.1° 2θ.15. The method of claim 13 , wherein the crystalline polymorph exhibits an x-ray powder ...

METHOD FOR TREATING INFECTIONS

The present invention relates to compounds that inhibit the activity of Hsp90 and methods of using these compounds for treating or preventing infection. 164-. (canceled)66. The Method of claim 65 , wherein Ris an optionally substituted naphthyl.70. The method of claim 65 , wherein the compound is administered with an additional therapeutic agent. This application claims the benefit of U.S. Provisional Application No. 60/852,795, filed Oct. 19, 2006 and U.S. Provisional Application No. 60/961,404, filed Jul. 19, 2007, the entire teachings of which are incorporated herein by reference.The invention relates to compounds that inhibit the activity of Hsp90 and methods for treating or preventing infections.Infectious diseases are still a major cause of death and disability worldwide. For example, The World Health Organization estimates that about 180 million people, some 3% of the world's population, are infected with hepatitis C virus (HCV); an estimated 2 million cases of (bacterial infection) occur annually in the U.S; and about 50 million (amoebic) infections are reported worldwide each year. Therefore, a need exists for new therapeutics that can treat or prevent infections caused by such things as fungi, bacteria, viruses, and parasites.Heat shock proteins (HSPs) are a class of chaperone proteins that are up-regulated in response to elevated temperature and other environmental stresses, such as ultraviolet light, nutrient deprivation, and oxygen deprivation. HSPs act as chaperones to other cellular proteins (called client proteins) and facilitate their proper folding and repair, and aid in the refolding of misfolded client proteins. There are several known families of HSPs, each having its own set of client proteins. The Hsp90 family is one of the most abundant HSP families, accounting for about 1-2% of proteins in a cell that is not under stress and increasing to about 4-6% in a cell under stress. Inhibition of Hsp90 results in degradation of its client proteins via ...

POLYMORPHIC, CRYSTALLINE AND MESOPHASE FORMS OF SODIUM 2-(5-BROMO-4-(4-CYCLOPROPYLNAPHTHALEN-1-YL)-4H-1,2,4-TRIAZOL-3-YLTHIO) ACETATE, AND USES THEREOF

Crystalline polymorphs and solid mesophase forms of sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate are described. In addition, pharmaceutical compositions and uses of such compositions for the treatment of a variety of diseases and conditions are provided. 19.-. (canceled)11. The crystalline polymorph of claim 10 , further characterized by a peak at 12.80° 2θ±0.1° 2θ.12. The crystalline polymorph of that exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in .13. The crystalline polymorph of claim 10 , characterized by an endothermic point onset claim 10 , as determined by differential scanning calorimetry at about 173° C.14. The crystalline polymorph of characterized by a differential scanning calorimetry pattern substantially the same as the differential scanning calorimetry pattern shown in .15. (canceled)16. A solid pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00010', 'claim 10'}, 'an effective amount of the crystalline polymorph of as an active ingredient; and'}at least one excipient or carrier.17. A method for treating or preventing hyperuricemia claim 10 , or a disease caused by elevated uric acid levels claim 10 , comprising administering an effective amount of the crystalline polymorph of .18. A method for treating or preventing gout comprising administering an effective amount of the crystalline polymorph of .1946.-. (canceled)47. A solid pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00013', 'claim 13'}, 'an effective amount of the crystalline polymorph of as an active ingredient; and'}at least one excipient or carrier.48. A method for treating or preventing hyperuricemia claim 13 , or a disease caused by elevated uric acid levels claim 13 , comprising administering an effective amount of the crystalline polymorph of .49. A method for treating or preventing gout comprising administering an effective amount of the ...

Preparation method of carfentrazone-ethyl

A preparation method of carfentrazone-ethyl comprises steps of: reacting 1-(5-amino-4-chloro-2-fluorophenyl)-4-difluoromethyl-3-methyl-1H-1,2,4-triazol-5-one with acrylic acid through a diazo arylation reaction to give 2-chloro-3-{2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,3-triazol-1-yl]-4-fluorophenyl}propionic acid; and reacting the 2-chloro-3-{2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,3-triazol-1-yl]-4-fluorophenyl}propionic acid with ethanol through an esterification reaction in a presence of an acidic catalyst to give carfentrazone-ethyl. 1. A preparation method of carfentrazone-ethyl , comprising steps of:(1) mixing 1 mol of substituted phenylamine with 16˜28 mol of organic solvent, stirring to dissolve, then introducing 2.4˜3.2 mol of hydrogen chloride into the mixture at a temperature between 0-5 ° C. and successively adding 4-12 mol of acrylic acid, 0.05 mol·0.10 mol of cuprous chloride, 0.3˜0.8 mol of alkali metal chloride and a 45% (wt/wt) aqueous solution of sodium nitrite which contains 1.2˜1.8 mol of sodium nitrite to react; after the reaction is completed, distilling to remove the organic solvent, adding solvent of benzene class, and washing respectively with water, acid and water; and then concentrating an organic layer under reduced pressure, cooling to crystallize, and filtrating by suction, to give 2-chloro-3-{2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorophenyl}propionic acid; and(2) adding 1 mol of the 2-chloro-3-{2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1 -yl]-4-fluorophenyl} propionic acid of the step (1), 4˜10 mol of ethanol and 0.03˜0.2 mol of an acid catalyst into 6˜12 mol of the solvent of benzene class; refluxing the reaction mixture until an esterification is completed; washing successively with water, with aqueous alkali base and then with water; and removing the solvent totally from the organic layer, to give a ...

NOVEL COMPOUNDS AND COMPOSITIONS AND METHODS OF USE

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid. 2. The compound of claim 1 , wherein:X is N.3. The compound of claim 1 , wherein:W is S or O.5. The compound of claim 4 , wherein:{'img': {'@id': 'CUSTOM-CHARACTER-00008', '@he': '2.12mm', '@wi': '4.57mm', '@file': 'US20140005136A1-20140102-P00001.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, 'represents a carbon-carbon double bond; and'}{'sup': 'P', 'Ris cyclopropyl.'}6. The compound of claim 1 , wherein:X is N;W is S; and{'sup': '1', 'sub': 3', '2', '2, 'Ris Cl, Br, I, optionally substituted methyl, CF, CHFor CHF.'}7. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R are not H.'}8. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R are H.'}9. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring, optionally containing 1 or 2 heteroatoms selected from N, S and O.'}10. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring.'}12. The compound of claim 11 , wherein:{'sup': '1a', 'Ris at least one amino acid.'}13. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a peptide.'}14. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a lipid.'}15. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a phospholipid.'}16. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a glycoside.'}17. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a nucleoside.'}18. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a nucleotide.'}19. The compound of claim 11 , wherein:{'sup': '1a', 'Ris an oligonucleotide.'}20. The compound of claim 11 , wherein:{'sup': ...

Suppression of Sars Replication by Sars Helicase Inhibitors

The present invention relates to compounds, compositions, and methods, for treating subjects suspected of needing treatment for a Nidovirales virus infection. In certain embodiments, the compounds comprise Nidovirales helicase inhibitors that do not significantly affect helicase ATPase enzymatic activity or nucleic acid binding activity of the helicase. 2. The method of claim 1 , wherein the one or more R groups are substituted by one claim 1 , two claim 1 , or three substituents selected from the group consisting of: halogens claim 1 , azido (—N3) claim 1 , cyano (—CN) claim 1 , hydroxyl (—OH) claim 1 , nitro (—NO2) claim 1 , alkyl claim 1 , aryl claim 1 , arylalkyl claim 1 , —O-alkyl claim 1 , and —O-aryl.3. The method of claim 2 , wherein the halogen is selected from the group consisting of —F claim 2 , —Cl claim 2 , —Br claim 2 , and —I.5. The method of claim 1 , wherein the Nidovirales virus infection is Severe Acute Respiratory Syndrome (SARS).6. The method of claim 1 , wherein the Nidovirales virus comprises a SARS-associated coronavirus (SARS-CoV).7. The method of claim 1 , wherein the Nidovirales virus comprises a Coronaviridae virus.8. The method of claim 1 , wherein the Nidovirales virus comprises a MERS-CoV.9. The method of claim 1 , wherein the Nidovirales virus comprises HCoV-229E and/or NL63.10. The method of claim 1 , comprising administering the compound of formula I by an oral route of administration.11. The method of claim 1 , comprising administering the compound of formula I by a non-oral route of administration.12. The method of claim 1 , wherein administering is selected from the group consisting of administering parenterally claim 1 , intravenously claim 1 , subcutaneously claim 1 , and intraperitoneally.13. The method of claim 1 , wherein administering is selected from the group consisting of administering transdermally claim 1 , sublingually claim 1 , and buccally.14. The method of claim 1 , wherein the subject is a mammal.15. The method of ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 1. (canceled)2. The process of claim 18 , where X is selected from pyrazole claim 18 , imidazole claim 18 , triazole claim 18 , benzotriazole claim 18 , furan claim 18 , pyrrole claim 18 , tetrazole claim 18 , pyrazine claim 18 , thiophene claim 18 , oxazole claim 18 , isoxazole claim 18 , thiazole claim 18 , isothiazole claim 18 , oxadiazole claim 18 , thiadiazole claim 18 , pyridazine claim 18 , pyridine claim 18 , pyrimidine claim 18 , pyran claim 18 , benzimidazole claim 18 , benzoxazole claim 18 , benzothiazole claim 18 , pyridylimidazole claim 18 , and pyridyltriazole.3. The process of claim 2 , where X is selected from pyrazole claim 2 , triazole claim 2 , benzotriazole claim 2 , tetrazole claim 2 , oxazole claim 2 , isoxazole claim 2 , thiazole claim 2 , pyridazine claim 2 , pyrimidine claim 2 , and pyridyltriazole.4. The process of claim 18 , where Ris selected from —ORand —NRR claim 18 , where Ris H claim 18 , Ris H or —OH claim 18 , and Ris H.7. The process of claim 18 , where Ris H.8. The process of claim 18 , where Ris absent or is selected from H; halo; —Calkylene-OH; —NH; —Calkyl; —CF; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; ═O; —NO; —C(CH)═N(OH); phenyl optionally substituted with one or two groups independently selected from halo claim 18 , —OH claim 18 , —CF claim 18 , —OCH claim 18 , —NHC(O)CH claim 18 , and phenyl; naphthalenyl; pyridinyl; pyrazinyl; pyrazolyl optionally substituted with methyl; thiophenyl optionally substituted with methyl or halo; furanyl; and —CH-morpholinyl; and Ris H.10. The process of claim 18 , where Ris absent or is selected from H; halo; —Calkylene-OH; —Calkyl; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; —NHC(O)R; ═O; phenyl optionally substituted with one or two groups independently selected from halo claim 18 , —OH claim 18 , and —OCH; pyridinyl; and pyrazinyl; Ris —Calkyl; ...

Lisofylline analogs and methods for use

The present invention provides analogs of a Lysofylline (LSF), and synthetic methods for the preparation of such analogs. The have the active side chain moiety (5-R-hydroxyhexyl) of LSF and can have greater potency and oral bioavailability than LSF.

METHODS FOR INHIBITING FASCIN

Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof. 6. The method of claim 1 , wherein Ris phenyl optionally substituted with one claim 1 , two claim 1 , or three groups chosen from halo and lower alkyl.7. The method of claim 1 , wherein Ris triazole.8. The method of claim 2 , wherein m is 0.9. The method of claim 1 , wherein Lis —N(R)S(O)—.10. The method of claim 1 , wherein Lis —S—.11. The method of claim 1 , wherein Xis OH and Xis O.12. The method of claim 1 , wherein Ris independently selected from the group consisting of OH claim 1 , halo claim 1 , lower alkyl claim 1 , and —OR.13. The method of claim 1 , wherein the compound is selected from5-(3,4-dichlorobenzyl)-1-(S,S,-dioxo-tetrahydrothiophen-3-yl)-1H-pyrazolo-[3,4-d]pyrimidin-4(5H)-one;N-(1-(4-(trifluoromethyl)benzyl)-1H-indazol-3-yl)furan-2-carboxamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-2,5-dimethylbenzenesulfonamide;N-(3(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-ethoxybenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-methoxybenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-ethylbenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-trimethylbenzenesulfonamide;(Z)—N-(3-(1H-1,2,4-triazol-3-ylthio)-4-oxonaphthalen-1(4H)-ylidene)benzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-bromobenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-2,4-dimethylbenzenesulfonamide;5-(3-chlorobenzyl)-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one;2-(4-oxo-1-(S,S,-dioxo-tetrahydrothiophen-3-yl)-1H-pyrazolo[3,4-d]-pyrimidin-5(4H)-yl)-N-(3-( ...

INHIBITION OF QUORUM SENSING-MEDIATED PROCESSES IN BACTERIA

Methods are provided for identifying molecules that can be used to positively and negatively manipulate quorum-sensing-mediated communication to control bacterial behavior. Small-molecule antagonists that disrupt quorum-sensing-mediated activities are identified. Methods are provided for disrupting detection of acyl-homoserine lactone autoinducer in Gram-negative bacteria by contacting the bacteria with the antagonists. Methods of inhibiting quorum sensing-mediated activity in Gram-negative bacteria are provided wherein the activity is pathogenicity, bioluminescence, siderophore production, type III secretion, or metalloprotease production. 2. The medical device of that is a catheter. This application is a continuation of U.S. patent application Ser. No. 12/995,476, filed Jan. 13, 2011, which is a National Stage of PCT Application No. PCT/US09/03348, which claims priority to U.S. Provisional Application No. 61/130,685, filed Jun. 2, 2008 and U.S. Provisional Application No. 61/188,310, filed Aug. 7, 2008, all of which are herein incorporated in their entirety.This invention was made with government support under Grant No. GM065859; Grant No. GM787552 and Grant No. AI054442 awarded by the National Institutes of Health and under Grant No. MCB0343821 and Grant No. MCB0639855 awarded by the National Science Foundation. The government has certain rights in the invention.The antagonist screen was partly funded with federal funds supplied to the National Cancer Institute's Initiative for Chemical Genetics, National Institutes of Health, under Contract No. N01-CO-12400 and has been performed with the assistance of the Chemical Biology Platform of the Broad Institute of Harvard and MIT. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Service, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.This invention relates to quorum sensing activities, ...

SUBSTITUTED IMIDAZOLE AND (1,2,4)TRIAZOLE COMPOUNDS AS FUNGICIDES

The present invention relates to compounds of the formula I 114-. (canceled)16: The compound of claim 15 , wherein A is N.17: The compound of claim 15 , wherein A is CH.18: The compound of claim 15 , wherein D is SR.19: The compound of claim 15 , wherein D is halogen.20: The compound of claim 17 , wherein D is H.21: The compound of claim 20 , wherein Ris selected from halogen claim 20 , OH claim 20 , CN claim 20 , nitro claim 20 , C-C-cycloalkyl and C-C-halocycloalkyl claim 20 , n+m is 1 claim 20 , 2 claim 20 , 3 claim 20 , 4 claim 20 , 5 claim 20 , 6 claim 20 , 7 claim 20 , 8 or 9 and for n=0 and m=1 claim 20 , Ris not 4-Cl claim 20 , 4-F or 4-Br claim 20 , and for n=1 with R=2-Cl and m=1 claim 20 , Ris not 4-Cl.22: The compound of claim 21 , wherein n is 1 claim 21 , 2 claim 21 , 3 or 4 and m is 1 claim 21 , 2 claim 21 , 3 claim 21 , 4 or 5 with the said proviso.23: The compound I of claim 15 , wherein D is SH claim 15 , A is N claim 15 , Ris H claim 15 , Ris CH claim 15 , (R)is 4-Cl and (R)is 2-Cl or 2-CF; the compounds I wherein D is SH claim 15 , A is N claim 15 , Ris H claim 15 , Ris CH(CH) claim 15 , (R)is 4-Cl and (R)is 2-Cl or 2-CF; the compounds I wherein D is SH claim 15 , A is N claim 15 , Ris H claim 15 , Ris cyclopropyl claim 15 , (R)is 4-Cl and (R)is 2-Cl or 2-CF; the compound I wherein D is SH claim 15 , A is N claim 15 , Ris H claim 15 , Ris C═CCH claim 15 , (R)is 4-Cl and (R)is 2-Cl; and the compound I wherein D is SH claim 15 , A is N claim 15 , Ris CH claim 15 , Ris CH claim 15 , (R)is 4-Cl and (R)is 2-CF.24: A composition comprising one compound of formula I claim 15 , as defined in claim 15 , an N-oxide or an agriculturally acceptable salt thereof.25: The composition according to claim 24 , comprising additionally a further active substance.26: A method for combating harmful fungi claim 24 , comprising treating the fungi or the materials claim 24 , plants claim 24 , the soil or seeds to be protected against fungal attack with an effective ...

S-triazolyl alpha-mercapto acetanilides as inhibitors of hiv reverse transcriptase

A series of S-triazolyl α-mercaptoacetanilides having general structure (1) are provided, where Q is CO 2 H, CONR 2 , SO 3 H, or SO 2 NR 2 . The compounds inhibit several variants of the reverse transcriptase of HIV, and are useful in the treatment of HIV infections.

SULFONYLDIAZOLES AND N-(FLUOROSULFONYL)AZOLES, AND METHODS OF MAKING THE SAME

The present disclosure provides methods for producing N-(fluorosulfonyl)azoles, sulfonyldiazoles, or related derivatives thereof, and the related products including N-(fluorosulfonyl)azoles, sulfonyldiazoles, and related derivatives thereof. For example, an N-(fluorosulfonyl)azole is obtained by reaction of sulfuryl fluoride with an azoles, an azolate salt, an N-silylazole, or a combination thereof. Symmetric and asymmetric sulfonyldiazoles are obtained by further reaction of such an N-(fluorosulfonyl)azole with azoles, azolate salts, or N-silylazoles. A sulfonyldiazole can be also produced by reacting sulfuryl fluoride with an azole, an N-silylazole, or a combination thereof in one pot. 1. A method , comprising:{'sub': 2', '2, 'reacting sulfuryl fluoride (SOF) with an azole or an azolate salt having a first azole base structure (Azole 1), wherein Azole 1 in a free form is protic; and'}{'sub': '2', 'isolating an N, N′-sulfonyldiazole (Azole 1-SO-Azole 1).'}2. The method of claim 1 , wherein the first azole base structure is selected from the group consisting of imidazole claim 1 , pyrazole claim 1 , 1 claim 1 ,2 claim 1 ,4-triazole claim 1 , benzimidazole claim 1 , benzotriazole claim 1 , indazole claim 1 , 2-methylimidazole claim 1 , 2-methylbenzimidazole claim 1 , and 3 claim 1 ,5-dimethylpyrazole.3. The method of claim 1 , wherein the azolate salt is an azole anion salt having an ion of a metal selected from the group consisting of lithium claim 1 , sodium claim 1 , potassium claim 1 , cesium claim 1 , magnesium claim 1 , and a combination thereof.4. The method of claim 1 , wherein the azolate salt is derived from a protic azole and a metal carbonate claim 1 , the metal being selected from the group consisting of lithium claim 1 , sodium claim 1 , potassium claim 1 , cesium claim 1 , magnesium claim 1 , and a combination thereof.5. The method of claim 1 , wherein the azolate salt is derived from a protic azole and a metal fluoride claim 1 , the metal being ...

Neprilysin inhibitors

In one aspect, the invention relates to compounds having the formula: where R 1 -R 6 , a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula XII: 128-. (canceled)30. The compound of claim 29 , wherein Ris H.31. The compound of claim 29 , wherein Ris selected from H claim 29 , —CHCHand —CHCH(CH).32. The compound of claim 31 , wherein Ris —CHCH.33. The compound of claim 30 , wherein Ris —CHCH.34. The compound of claim 29 , wherein P is selected from H claim 29 , t-butoxycarbonyl claim 29 , trityl claim 29 , benzyloxycarbonyl claim 29 , 9-fluorenylmethoxycarbonyl claim 29 , formyl claim 29 , trimethylsilyl and t-butyldimethylsilyl.35. The compound of claim 34 , wherein P is H.36. The compound of claim 33 , wherein P is H.37. The compound of claim 29 , wherein Ris H.38. The compound of claim 29 , wherein Ris F.39. The compound of claim 36 , wherein Ris F.40. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluoro-biphenyl-4-yl)-2-hydroxypentanoic acid or a pharmaceutically acceptable salt thereof.41. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester or a pharmaceutically acceptable salt thereof.42. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo-[1 claim 29 ,3]dioxol-4-ylmethyl ester or a pharmaceutically acceptable salt thereof.43. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 2 claim 29 ,2 claim 29 ,3 claim 29 ,3 claim 29 ,3-pentafluoropropyl ester or a pharmaceutically acceptable salt thereof.44. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid butyryloxymethyl ester or a pharmaceutically acceptable salt thereof.45. A method of performing a coupling reaction claim 29 , comprising contacting the compound of with a ...

Hydantoin containing deoxyuridine triphosphatase inhibitors

Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

METHODS FOR INHIBITING FASCIN

Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof. 6. The method of claim 1 , wherein Ris phenyl optionally substituted with one claim 1 , two claim 1 , or three groups chosen from halo and lower alkyl.7. The method of claim 1 , wherein Ris triazole.8. The method of claim 2 , wherein m is 0.9. The method of claim 1 , wherein Lis —N(R)S(O)—.10. The method of claim 1 , wherein Lis —S—.11. The method of claim 1 , wherein Xis OH and Xis O.12. The method of claim 1 , wherein Ris independently selected from the group consisting of OH claim 1 , halo claim 1 , lower alkyl claim 1 , and —OR.13. (canceled)16. The method of claim 15 , wherein Wis S.17. The method of claim 14 , wherein Ris phenyl optionally substituted with halo or alkyl.18. The method of claim 14 , wherein Ris phenyl optionally substituted with halo or alkyl.19. The method of claim 14 , wherein Rand Rare phenyl.20. The method of claim 14 , wherein Ris methyl claim 14 , phenyl claim 14 , or benzyl.2122-. (canceled)2467-. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/972,649, filed on Aug. 21, 2013, which claims the benefit of U.S. Provisional Patent Application No. 61/692,177, filed on Aug. 22, 2012, and U.S. Provisional Patent Application No. 61/778,015, filed on Mar. 12, 2013. The entire contents of the foregoing applications are hereby incorporated herein by reference in their entireties.The technology described herein was developed with funds from National Institutes of Health Grant No. R01 CA136837. The United States Government has certain rights to the technology.The present technology relates generally to methods for treating or preventing cancer.In recent years, progress has ...

PHASE-TRANSFER CATALYSED FORMATION OF N-(SUBSTITUTED PHENYL) SULFONAMIDES IN WATER

A new process for making agrochemically important N-[2,4-dichloro-5-[4-(difluoro methyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl] phenyl]methanesulfonamide by reacting 1-(5-amino-2,4-dichlorophenyl)-4,5-dihydro-4-difluoromethyl-3-methyl-1,2,4-triazol-5(1H)-one and methanesulfonyl chloride in water using an inorganic base to dynamically control the reaction pH and in the presence of a phase transfer catalyst suspended in an 1:1 aromatic solution. 1. A process to produce N-[2 ,4-dichloro-5-[4-(difluoromethyl)-4 ,5-dihydro -3-methyl-5-oxo-1H-1 ,2 ,4-triazol-1-yl]phenyl]methanesulfonamide from 1-(5-amino-2 ,4-di chlorophenyl)-4 ,5-dihydro-4-difluoromethyl-3-methyl-1 ,2 ,4 -triazol-5(1H)-one and methane sulfonyl chloride in water with an inorganic base under controlled pH conditions and with the use of an alkylammonium halide phase transfer catalyst suspended in an aromatic solvent.2. A process according to claim 1 , wherein the reaction is preferably carried out between 5 degree centigrade and 15 degree centigrade.3. A process according to claim 1 , wherein the pH in the reaction is dynamically maintained in the range between 7.5 and 8.5 using an aqueous inorganic base.4. A process according to claim 3 , wherein the inorganic base is preferably sodium carbonate and potassium carbonate.5. A process according to claim 1 , wherein the methanesulfonyl chloride is preferably added simultaneously with the aqueous inorganic base into the suspension of the 1-(5-amino-2 claim 1 ,4-dichlorophenyl)-4 claim 1 ,5-dihydro-4-difluoromethyl-3-methyl-1 claim 1 ,2 claim 1 ,4 -triazol-5(1H)-one and alkylammonium halide phase transfer catalyst in an aromatic solvent.6. A process according to wherein the phase transfer catalyst and aromatic solvent are preferably used in a 1:1 ratio.7. A process according to wherein the phase transfer catalyst used is preferably tetrabutylammonium bromide or tetrapropylammonium chloride.8. A process according to wherein the aromatic solvent used is ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 14-. (canceled)5. The compound of claim 24 , where Ris selected from —ORand —NRR claim 24 , Ris H claim 24 , Ris H or —OH claim 24 , and Ris H.8. The compound of claim 24 , where Ris —NRR claim 24 , where Ris H and Ris H.9. The compound of claim 24 , where Ris H.1015-. (canceled)16. The compound of claim 24 , where a is 0; or a is 1 and Ris 3-chloro.17. The compound of claim 24 , where b is 0; orb is 1 and Ris 3′-chloro claim 24 , 3′-methyl claim 24 , or 2′-methoxy; or b is 2 and Ris 2′-fluoro-5′-chloro claim 24 , 2′ claim 24 ,5′-dichloro claim 24 , 2′-methyl-5′-chloro claim 24 , or 3′-chloro-5′-hydroxy.18. The compound of claim 24 , where the methylene linker on the biphenyl is substituted with 2 methyl groups.20. The compound of claim 24 , where{'sup': 1', '7, 'Ris —OR;'}{'sup': '2', 'Ris H;'}X is selected from pyrazole, triazole, benzotriazole, isoxazole, pyridazine, pyrimidine, and pyridyltriazole;{'sup': 3', '20', '21', '22', '23', '24, 'sub': 0-5', '1-6', '3', '3-7', '0-2', '1-6', '0-1', '3', '3, 'Ris selected from H; halo; —Calkylene-OH; —Calkyl; —CF; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; ═O; —C(CH)═N(OH); phenyl optionally substituted with one or two groups independently selected from halo, —OH, and —OCH; pyridinyl; pyrazinyl; and thiophenyl substituted with methyl or halo;'}{'sup': 4', '35', '3', '4, 'sub': 1-6', '1-2', '2', '2', '2', '1-3, 'Ris selected from H; —OH; —Calkyl; —Calkylene-COOR; —CHCH(OH)CHOH; pyridinyl; and phenyl optionally substituted with one halo group; or Rand Rare taken together to form -phenylene-O—(CH)—;'}{'sup': '5', 'a is 0; or a is 1 and Ris 3-chloro;'}{'sup': 6', '6, 'b is 0; or b is 1 and Ris 3′-chloro, 3′-methyl, or 2′-methoxy; or b is 2 and Ris 2′-fluoro-5′-chloro, 2′,5′-dichloro, 2′-methyl-5′-chloro, or 3′-chloro-5′-hydroxy;'}{'sup': '20', 'sub': '1-6', 'Ris —Calkyl;'}{'sup': '21', 'Ris H;'}{'sup': 22', '23', '22', ' ...

COMPOUND HAVING ENHANCING ACTIVITY FOR GLUCAGON-LIKE PEPTIDE-1 RECEPTOR ACTIONS

Compounds represented by formula (I): 2. The compound or salt according to claim 1 , wherein{'sub': '6-14', 'A is a Caryl group or a 5- or 6-membered monocyclic aromatic heterocyclic group, each of which is optionally further substituted,'}L is a bond or a methylene group,Q is an oxygen atom,{'sup': 4', '5, 'sub': '1-6', 'Rand Rare the same or different and are each independently a hydrogen atom or an optionally substituted Calkyl group, and'}n is 1 or 2.3. The compound or salt according to claim 1 , wherein{'sub': 1-6', '1-6', '1-6', '1-3', '1-6', '1-6', '1-6', '1-3, 'A is a phenyl group optionally further substituted by the same or different 1 to 5 substituents selected from the group consisting of a halogen atom, a hydroxy group, a carboxy group, a sulfanyl group, an optionally substituted Calkyl group, an optionally substituted Calkoxy group, an optionally substituted amino group, a Calkylthio group optionally substituted by a halogen atom, and a Calkylenedioxy group, or a pyridyl group optionally further substituted by the same or different 1 to 4 substituents selected from the group consisting of a halogen atom, a hydroxy group, a carboxy group, a sulfanyl group, an optionally substituted Calkyl group, an optionally substituted Calkoxy group, an optionally substituted amino group, a 4- to 7-membered monocyclic non-aromatic heterocyclic group, a Calkylthio group optionally substituted by a halogen atom, and a Calkylenedioxy group,'}{'sub': 1-6', '1-6', '1-6', '1-3, 'B is a benzene ring optionally further substituted by the same or different 1 to 4 substituents selected from the group consisting of a halogen atom, a hydroxy group, a sulfanyl group, an optionally substituted Calkyl group, an optionally substituted Calkoxy group, an optionally substituted amino group, a Calkylthio group optionally substituted by a halogen atom, a Calkylenedioxy group, and a 4- to 7-membered monocyclic non-aromatic heterocyclic group,'}L is a bond or a methylene group,{'sup': '1', ...

COMPOUNDS AND COMPOSITIONS FOR USE IN AUGMENTATION OF GLUCOSE

The present invention is directed to compounds such as: formula wherein linker is independently selected from the group consisting of —S—, —S—S—, —S—(CH2)n—, —NH—, —NH—(CH2)n—, —O—, —S02-, arylene, heteroarylene; R1 is selected from the group consisting of straight or branched C4-C20 alkyl, straight or branched C4-C20 alkenyl, straight or branched C4-C20 alkynyl, each optionally interrupted with at least one NH, C5-C7 saturated cycloalkyl or heteroalkyl ring, C5-C12 aromatic or heteroaromatic ring, each optionally substituted with at least one group selected from —COOH, —NH2, C1-C8 alkoxy, C1-C5 amidyle, C1-C5 carboxyl, halogen; and R2 is independently selected from the group consisting of H, OH, SH, NH2, NO2, halogen, CN, C1-C8 alkoxy, C1-C5 carboxylic acid, straight or branched C1-C8 alkyl, straight or branched C2-C10 alkenyl, straight or branched C2-C12 alkynyl each optionally substituted by at least one substituent selected from the group consisting of C1-C5 alkoxy, C1-C5 carboxylic acid, OH, SH, NH2, halogen; and compositions for use in the treatment of diabetes and related disorders. 132-. (canceled)34. A compound of claim 33 , wherein at least one of Xto Xis O.35. A compound of claim 33 , wherein at least two of Xto Xare O.36. A compound of claim 33 , wherein least one of Xto Xis CHR.37. A compound of claim 33 , wherein Ris aryl or heretroaryl.38. A compound of claim 33 , wherein Y and Z are identical.39. A compound of claim 33 , wherein Y and Z are S.41. A compound of claim 33 , being used as a medicament.42. A composition comprising a compound according to .43. A method of treating or preventing a condition claim 33 , symptom or disease associate with elevated blood glucose levels in a subject in need thereof claim 33 , said method comprising administering to said subject a compound of .44. A method for the treatment or prevention of at least one condition selected from hyperglycemia claim 33 , diabetes claim 33 , altered insulin secretion claim 33 , ...

EPOXYEICOSATRIENOIC ACID ANALOGS AND METHODS OF MAKING AND USING THE SAME

Compounds and compositions comprising epoxyeicosatrienoic acid (EET) analogs that act as EET agonists and are useful as medications in the treatment of drug-induced nephrotoxicity, hypertension and other related conditions. Methods of making and using the compounds and compositions are further described. 5. A composition comprising a compound of and a pharmaceutically acceptable carrier.6. A method of reducing hypertension in a subject claim 1 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 1 , wherein hypertension in said subject is reduced.7. (canceled)8. (canceled)9. A method of reducing nephrotoxicity in a subject claim 1 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 1 , wherein nephrotoxicity in said subject is reduced.10. The method of claim 9 , wherein the nephrotoxicity is drug-induced.11. The method of claim 10 , wherein the nephrotoxicity is cisplatin-induced.12. (canceled)13. (canceled)14. A method of reducing cisplatin nephrotoxicity in a subject claim 1 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 1 , wherein cisplatin nephrotoxicity in said subject is reduced.15. (canceled)16. (canceled)17. A composition comprising a compound of and a pharmaceutically acceptable carrier.18. A method of reducing hypertension in a subject claim 4 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 4 , wherein hypertension in said subject is reduced.19. A method of reducing nephrotoxicity in a subject claim 4 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 4 , wherein nephrotoxicity in said subject is reduced.20. The method of claim 19 , wherein the nephrotoxicity is drug-induced.21. The method of claim 20 , wherein the nephrotoxicity is cisplatin-in-induced.22. A method of ...

BICYCLO (3.1.0) HEXANE-2, 6-DICARBOXYLIC ACID DERIVATIVES AS MGLU2 RECEPTOR AGONIST

The present invention provides novel mGlu2 agonists useful in the treatment of bipolar disorder, schizophrenia, and generalized anxiety disorder. 3. The compound according towherein{'sup': '2', 'sub': 3', '3, 'Ris 2,2-dimethyl-propionyloxymethyl, or benzyl optionally substituted with one to two fluorine atoms, —CF, or —OCH; and'}{'sup': '3', 'sub': 3', '3, 'Ris 2,2-dimethyl-propionyloxymethyl, or benzyl optionally substituted with one to two fluorine atoms, —CF, or —OCH;'}or a pharmaceutically acceptable salt thereof.5. The compound according to wherein Rand Rare each hydrogen claim 1 , and Ris other than hydrogen; or a pharmaceutically acceptable salt thereof.6. (canceled)7. The compound according to wherein R claim 1 , Rand Rare each hydrogen; or a pharmaceutically acceptable salt thereof.8. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent claim 1 , or excipient.9. (canceled)10. A method of treating a psychiatric disorder selected from the group consisting of bipolar disorder claim 1 , schizophrenia claim 1 , and generalized anxiety disorder claim 1 , comprising administering to a patient in need thereof an effective amount of a compound according to claim 1 , or pharmaceutically acceptable salt thereof.11. The method of claim 10 , wherein the psychiatric disorder is bipolar disorder.12. The method of claim 10 , wherein the psychiatric disorder is schizophrenia.13. The method of wherein the psychiatric disorder is generalized anxiety disorder.1419-. (canceled) The present invention relates to mGlu2 receptor agonist compounds, particular prodrugs thereof, and their salts as well as pharmaceutical compositions and therapeutic uses of such compounds, particular prodrugs, and their salts.L-Glutamate is the major excitatory neurotransmitter in the central nervous system and is referred to as an excitatory amino acid. The ...

PIPERIDINE/PIPERAZINE DERIVATIVES

The invention further relates to a DGAT inhibitor of formula 36-. (canceled)9. The compound as claimed in wherein Rand Reach independently represent halo or Calkyl.10. The compound as claimed in wherein both Rand Rrepresent halo.11. The compound as claimed in wherein Rrepresents HetCalkyl.12. The compound as claimed in wherein Rrepresents hydrogen.13. The compound as claimed in wherein Rrepresents hydrogen; Rrepresents a 6 membered aromatic monocyclic heterocycle; wherein said heterocycle may optionally be substituted with one or two substituents claim 1 , each substituent independently being selected from the group consisting of oxo claim 1 , Calkyl optionally substituted with Calkyl-oxycarbonyl; hydroxyCalkyl optionally substituted with aryl; mono-or di(Calkyl)-amino; RRN-Calkyl; Het-NRx- claim 1 , Ccycloalkyl; Ccyclo-alkylCalkyl; aryl; arylCalkyl; aryl-C(═O)—Calkyl claim 1 , and Het; Rrepresents Ccyclo-alkyl claim 1 , phenyl claim 1 , naphthalenyl claim 1 , 1 claim 1 ,3-benzodioxolyl claim 1 , or a 6-membered aromatic heterocycle containing 1 or 2 N atoms claim 1 , wherein said Ccycloalkyl claim 1 , phenyl claim 1 , naphthalenyl claim 1 ,{'sub': 1-6', '1-6, '1,3-benzodioxolyl or 6-membered aromatic heterocycle may optionally be substituted with one or two substituents, each substituent independently selected from the group consisting of hydroxyl; carboxyl; halo; Calkyl optionally substituted with hydroxy, polyhaloCa1kyl,'}{'sub': 1-6', '1-6', '1-6', '1-4', '1-4', '1-4', '1-4', '1-4', '1-6', '1-6', 'p', '1-6, 'sup': 4', '5', '8, 'Calkyloxy; Calkylthio; Calkyloxycarbonyl; mono-or di(Calkyl)amino; Calkylcarbonylamino; Het; and HetCalkyl; Rrepresents hydrogen or Calkyl; Rrepresents hydrogen or Calkyl; Rrepresents hydrogen; aryl represents phenyl or phenyl substituted with at least one substituent, said substituent being selected from the group consisting of halo; Calkyl; and Calkyloxy; Het represents a monocyclic non-aromatic or aromatic heterocycle containing at ...

Crystalline form of 4-amino-N-tert-butyl-4,5-dihydro-3-isopropyl-5-oxo-1,2,4-1H-triazole-1-carboxamide and a process for producing thereof

The invention provides a novel crystalline form of 4-amino-N-tert-butyl-4,5-dihydro-3-isopropyl-5-oxo-1,2,4-1H-triazole-1-carboxamide and a process for preparation of said crystalline form. The invention also relates to formulations and method for controlling weeds using said formulations. 2. The crystalline form as claimed in designated as Form C is further characterized by an X-ray powder diffractogram pattern having at least six of the following reflections values 6.8 claim 1 , 7.0 claim 1 , 7.6 claim 1 , 8.3 claim 1 , 11.2 claim 1 , 11.3 claim 1 , 12.4 claim 1 , 12.8 claim 1 , 15.6 claim 1 , 16.5 claim 1 , 16.6 claim 1 , 17.4 claim 1 , 17.5 claim 1 , 18.5 claim 1 , 19.6 claim 1 , 20.1 claim 1 , 23.5 claim 1 , 24.2 and 26.7 degrees 2θ (±0.2 degrees).3. A process for production of a crystalline form of 4-amino-N-tert-butyl-4 claim 1 ,5-dihydro-3-isopropyl-5-oxo-1 claim 1 ,2 claim 1 ,4-1H-triazole-1-carboxamide claim 1 , comprising:i) providing a solution of 4-amino-N-tert-butyl-4,5-dihydro-3-isopropyl-5-oxo-1,2,4-1H-triazole-1-carboxamide in an organic solvent;ii) effecting crystallisation by subjecting said solution to pre-determined crystallisation conditions thereby obtaining said crystalline form C.4. A process for the production of a crystalline form C of 4-amino-N-tert-butyl-4 claim 3 ,5-dihydro-3-isopropyl-5-oxo-1 claim 3 , 2 claim 3 ,4-1H-triazole-1-carboxamide as claimed in wherein said process comprisesi) providing a solution of 4-amino-N-tert-butyl-4,5-dihydro-3-isopropyl-5-oxo-1,2,4-1H-triazole-1-carboxamide in an organic solvent at a first temperature;ii) effecting crystallisation by subjecting the said solution to a second temperature at a pre-determined rate thereby obtaining said crystalline form C.5. The process as claimed in wherein said first temperature is in a range from about 30° to about 100° C.6. The process as claimed in wherein said second temperature is in a range from about −20° to about 30° C.7. The process as claimed in wherein said ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 128-. (canceled)29. (2R ,4R)-5-Biphenyl-4-yl-4-{[5-(3-carbamoylpyrrolidine-1-carbonyl)-2H-pyrazole-3-carbonyl]-amino}-2-hydroxy-pentanoic acid or a pharmaceutically acceptable salt thereof.30. (2R ,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[5-(4-hydroxypiperidine-1-carbonyl)-2H-pyrazole-3-carbonyl]-amino}-pentanoic acid or a pharmaceutically acceptable salt thereof.31. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.32. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.33. The pharmaceutical composition of claim 31 , further comprising an ATreceptor antagonist.34. The pharmaceutical composition of claim 32 , further comprising an ATreceptor antagonist.35. The pharmaceutical composition of claim 33 , wherein the ATreceptor antagonist is selected from abitesartan claim 33 , azilsartan claim 33 , azilsartan medoxomil claim 33 , benzyllosartan claim 33 , candesartan claim 33 , candesartan cilexetil claim 33 , elisartan claim 33 , embusartan claim 33 , enoltasosartan claim 33 , eprosartan claim 33 , EXP3174 claim 33 , fonsartan claim 33 , forasartan claim 33 , glycyllosartan claim 33 , irbesartan claim 33 , isoteoline claim 33 , losartan claim 33 , milfasartan claim 33 , olmesartan claim 33 , olmesartan medoxomil claim 33 , opomisartan claim 33 , pratosartan claim 33 , ripisartan claim 33 , saprisartan claim 33 , saralasin claim 33 , sarmesin claim 33 , TAK-591 claim 33 , tasosartan claim 33 , telmisartan claim 33 , valsartan claim 33 , and zolasartan.36. The pharmaceutical composition of claim 34 , wherein the ATreceptor antagonist is selected from abitesartan claim 34 , azilsartan claim 34 , azilsartan medoxomil claim 34 , benzyllosartan claim 34 , candesartan claim 34 , candesartan cilexetil claim 34 , elisartan claim 34 , embusartan claim 34 , enoltasosartan claim 34 , eprosartan claim 34 , EXP3174 claim 34 , ...

PROCESSES FOR THE SYNTHESIS OF SULFENTRAZONE

Disclosed are processes for the synthesis of sulfentrazone, which provide a high conversion of sulfentrazone amine and high yield of the final sulfentrazone product. 2. The process of claim 1 , wherein the compound of Formula-A is 2-methylimidazole claim 1 , 4-methylimidazole claim 1 , 5-methylimidazole claim 1 , 2-ethylimidazole claim 1 , 4-ethylimidazole claim 1 , 5-ethylimidazole claim 1 , 2-phenylimidazole claim 1 , 4-phenylimidazole or 5-phenylimidazole.3. The process of claim 1 , wherein the compound of Formula-B is formamidine claim 1 , acetamidine or salts thereof.4. The process of claim 3 , wherein the compound of Formula-B is formamidine hydrochloride claim 3 , acetamidine hydrochloride claim 3 , formamidine sulfate claim 3 , acetamidine sulfate claim 3 , formamidine phosphate or acetamidine phosphate.5. The process of claim 1 , wherein the process is carried out in a solvent.6. The process of claim 2 , wherein the solvent is selected from aromatic claim 2 , alkane claim 2 , and alkene solvents claim 2 , and any mixtures thereof.7. The process of claim 3 , wherein the solvent is selected from toluene claim 3 , xylene claim 3 , diethylbenzene claim 3 , and any mixtures thereof.8. The process of claim 4 , wherein the solvent is toluene.9. The process of claim 1 , wherein the process is carried out at an elevated temperature claim 1 , with the preferred temperature ranging from about 110° C. to about 160° C.10. The process of claim 6 , wherein the temperature ranges from about 120° C. to about 130° C.11. The process of claim 1 , wherein the process is carried out at atmospheric pressure or higher pressure.12. The process of claim 1 , wherein the process is carried out at a pressure ranging from about 0.15 MPa to about 1 MPa.13. The process of claim 1 , wherein the catalyst is present in an amount ranging from about 0.01 to about 0.2 molar equivalents of sulfentrazone amine14. The process of claim 13 , wherein the catalyst is imidazole.15. The process of claim ...

METHOD FOR THE PREPARATION OF A 2,4,5-TRISUBSTITUTED 1,2,4-TRIAZOLONE

The present invention provides methods for the preparation of Compound (I): Compound (I), the use of intermediates for the preparation of said compound and its crystalline form A. 3. The method of or , wherein PG is a tetrahydropyranylether and further comprising acidic conditions as reagents for cleaving the protecting group tetrahydropyranylether.4. The method according to claim 3 , wherein said acidic conditions are accomplished by addition of phosphoric acid and methanol.5. The method according to - claim 3 , wherein said suitable base is pyridine.6. The method according to - claim 3 , further comprising generation of an acid chloride.7. The method according to wherein the reagent for generating the acid chloride is phosphoryl chloride:8. The method according to or wherein the acid chloride or an activated acid is generated in situ.9. The method of - comprising isolating compound (A9) and subsequently cleaving the protecting group.11. The method according to - further comprising a step for isolation of Compound (I).12. The method according to further comprising a step for purification of Compound (I).13. The method according to - claim 11 , further comprising a micronization step.18. The form of the compound of characterized by a X-ray powder diffractogram measured at 25° C. and with Cu—K alpha 1 as radiation source displaying at least the following reflections claim 17 , quoted as 2Θ value±0.2°:17.2 claim 17 , 18.3 claim 17 , 19.1 claim 17 , 21.0 claim 17 , 25.2.19. A pharmaceutical composition comprising crystalline form A of Compound (I) according to and optionally comprising further pharmaceutically acceptable excipients.20. Use of a pharmaceutical composition according to for the treatment of a hyperproliferative disease claim 19 , such as cancer.21. Use according to claim 20 , wherein the cancer disease is selected from cancers of breast; brain; digestive tract; eye; head and neck; haematological malignancies including leukemias claim 20 , lymphomas claim ...

NITRIFICATION INHIBITORS

The present invention relates to novel nitrification inhibitors of formula I. Moreover, the invention relates to the use of these novel nitrification inhibitors for reducing nitrification, as well as agrochemical mixtures and compositions comprising the nitrification inhibitors. Further encompassed by the present invention are methods for reducing nitrification comprising the treatment of plants, soil and/or loci with said nitrification inhibitors, and methods for treating a fertilizer or a composition by applying said nitrification inhibitor. 116-. (canceled)18: The compound of claim 17 , wherein in said compound of formula I claim 17 , A is phenyl or a 6-membered hetaryl claim 17 , preferably phenyl claim 17 , wherein the aromatic ring may in each case be unsubstituted or may be partially or fully substituted by substituents claim 17 , which are independently of each other selected from R.19: The compound of claim 17 , wherein in said compound of formula I claim 17 , Rand Rboth represent hydrogen.20: The compound of claim 17 , wherein in said compound of formula I claim 17 , Ris hydrogen claim 17 , C-C-haloalkyl or ethinylhydroxymethyl claim 17 , and preferably Ris hydrogen.21: The compound of claim 17 , wherein in said compound of formula I claim 17 , R claim 17 , if present claim 17 , is{'sup': a', 'b', 'c', '1', 'c', '1', 'c', '1', 'c', '1', 'a', 'b', '2', '1', '2', '1', 'a', 'b', 'g', 'd', 'e', 'f, 'sub': 2', '2', '1', '6', '2', '6', '1', '4', '1', '4', '2', '4', '1', '2', '2', '4, '(i) halogen, CN, NRR, OR, C(═Y)R, C(═Y)OR, C(═Y)SR, C(═Y)NRR, YC(═Y)R, YC(═Y)NRR, NRN═C(R)(R), S(═O)R, NO, C-C-alkyl, C-C- C-C-haloalkyl, C-C-alkoxy, C-C-alkynyl-C-C-hydroxyalkyl, C-C-alkynyloxy;'}{'sub': 2', '4', '2', '4', '1', '4', '2', '4, 'sup': 1', 'c', '2', '1', 'c, '(ii) C-C-alkenylene-C(═Y)R, C-C-alkenylene-Y—C(═Y)R, wherein the C-C-alkylene or C-C-alkenylene chain may in each case be unsubstituted or may be partially or fully substituted by CN or halogen;'}{'sup': 'h', '( ...

CATHEPSIN-D AND ANGIOGENESIS INHIBITORS AND COMPOSITIONS THEREOF FOR TREATING BREAST CANCER

Cathepsin-D and angiogenesis inhibitors and compositions thereof for treating breast cancer are provided. More particularly, the embodiments relate to the design and synthesis of inhibitors of Cathepsin D, which exhibits antiproliferative activity and also inhibits angiogenesis. Also provided are compositions thereof for treating breast cancer. 112-. (canceled)14. The compound as claimed in claim 13 , wherein the C-Calkyl is CH.15. The compound as claimed in claim 13 , wherein Ris phenyl or benzthiazolyl optionally substituted with one or more substituents selected from CH claim 13 , OCH claim 13 , Cl claim 13 , F claim 13 , Br claim 13 , OH claim 13 , CONH claim 13 , NH claim 13 , HNCOCH claim 13 , NO claim 13 , COCH claim 13 , COOH claim 13 , CF claim 13 , and CN.16. The compound as claimed in claim 13 , wherein the compound is selected from:N-(5-chloro-2-methoxyphenyl)-2-((5-((m-tolylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-Phenyl-2-((5-((m-tolylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(3-fluorophenyl)-2-((5-((m-tolylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(3-bromophenyl)-2-((5-((m-tolylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(4-methoxyphenyl)-2-((5-((m-tolylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(3,4-dichlorophenyl)-2-((5-((m-tolylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(3,5-dimethoxyphenyl)-2-((5-((m-tolylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(2-chloro-5-(trifluoromethyl)phenyl)-2-((5-((m-tolylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-phenyl-2-((5-((phenylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(3-fluorophenyl)-2-((5-((phenylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(3-bromophenyl)-2-((5-((phenylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(4-methoxyphenyl)-2-((5-((phenylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(3,4-dichlorophenyl)-2-((5-((phenylamino)methyl)-1H-1,2,4-triazol-3-yl)thio)acetamide;N-(3,5- ...

METHOD FOR OBTAINING SOLUTIONS OF OTA IN A CONCENTRATED SULFURIC ACID MEDIUM; SAID SOLUTIONS; AND METHOD FOR PREPARING ONTA

A method for obtaining solutions that contain 1,2,4-triazole-5-one (OTA) in concentrated sulphuric acid, includes using 3-amino-1,2,4-triazole (ATA) as a precursor of OTA. There is also provided a method for preparing 3-nitro-1,2,4-triazole-5-one (4) (ONTA) from the solutions. 2. The process as claimed in claim 1 , wherein said concentrated sulfuric acid includes at least 75% by weight of sulfuric acid.3. The process as claimed in claim 1 , wherein the concentration of said 3-amino-1 claim 1 ,2 claim 1 ,4-triazole in the concentrated sulfuric acid is between 0 claim 1 ,3 and 2 mol/l.4. The process as claimed in of claim 1 , wherein said at least one nitrite is chosen from organic nitrites claim 1 , alkali metal nitrites and alkaline earth metal nitrites.5. The process as claimed in claim 1 , wherein the nitrite(s)/3-amino-1 claim 1 ,2 claim 1 ,4-triazole molar ratio is between 1 and 26. The process as claimed in claim 1 , wherein said at least one nitrite is reacted with said 3-amino-1 claim 1 ,2 claim 1 ,4-triazole at a temperature between 0° C. and 10° C.7. The process as claimed in claim 1 , wherein said heat treatment comprises two phases:a first phase of rise in temperature, carried out with control of the release of gas, so as to prevent any overflowing, up to a temperature T of at least 50° C., anda second phase of maintaining at said temperature T.8. The process as claimed in claim 7 , wherein the rise in temperature of the first phase is carried out according to a gradient of 9° C./h to 16° C./h.9. A solution of 1 claim 1 ,2 claim 1 ,4-triazol-5-one in concentrated sulfuric acid claim 1 , obtainable by the process as claimed in .10. A process for the preparation of 3-nitro-1 claim 1 ,2 claim 1 ,4-triazol-5-one claim 1 , the process comprising:{'claim-ref': [{'@idref': 'CLM-00009', 'claim 9'}, {'@idref': 'CLM-00001', 'claim 1'}], 'a) making available a solution of 1,2,4-triazol-5-one in concentrated sulfuric acid as claimed in or producing a solution of 1,2, ...

SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME

The present invention provides for certain sulfonyl ureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome. Such compounds are useful in the treatment of a wide range of disorders in which the inflammation process, or more specifically the NLRP3 inflammasome, have been implicated as being a key factor. 2. The compound of wherein Ris selected from the group consisting of Cor Ccycloalkyl claim 1 , 5-membered or 6-membered heteroaryl claim 1 , bicyclic heteroaryl wherein at least one ring is heteroaryl claim 1 , phenyl claim 1 , biphenyl claim 1 , phenylheterocyclyl claim 1 , 5-membered or 6-membered heterocyclyl claim 1 , and heterocyclylcycloalkyl claim 1 , all of which may be optionally substituted.3. The compound of or wherein Ris selected from the group consisting of pyrazole claim 1 , furan claim 1 , tetrahydrofuran claim 1 , tetrahydropyran claim 1 , pyran claim 1 , pyrrolidine claim 1 , pyrrole claim 1 , triazole claim 1 , tetrazole claim 1 , imidazole claim 1 , pyridine claim 1 , morpholine claim 1 , piperazine claim 1 , piperidine claim 1 , substituted phenyl claim 1 , phenylheteroaryl claim 1 , phenylheterocyclyl claim 1 , biphenyl claim 1 , quinoline claim 1 , isoquinoline claim 1 , naphthyl claim 1 , pyrazine and pyrimidine claim 1 , all of which may be optionally substituted as appropriate.4. The compound of any one of the preceding claims wherein Ris 5-membered heterocyclyl or heteroaryl claim 1 , each of which may be optionally substituted claim 1 , comprising at least one ring heteroatom selected from N claim 1 , O and S.5. The compound of wherein Ris 5-membered nitrogen heterocyclyl or 5-membered nitrogen heteroaryl claim 4 , each of which may be optionally substituted.6. The compound of or wherein Ris 5-membered heterocyclyl or 5-membered heteroaryl claim 4 , each of which may be optionally substituted claim 4 , comprising at least two ring nitrogen atoms.7. ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 131-. (canceled)32: A compound selected from:(a) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid;(b) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid ethyl ester;(c) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester;(d) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 2-morpholin-4-yl-ethyl ester;(e) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 2-methoxy-ethyl ester;(f) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 2-(2-methoxy-ethoxy)-ethyl ester;(g) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 2-methanesulfonyl-ethyl ester;(h) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid isopropyl ester;(i) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 2-dimethylamino-ethyl ester;(j) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid butyl ester;(k) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid propyl ester;(l) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 2-piperidin-1-yl-ethyl ester;(m) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 3-methyl-butyl ester;(n) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid pentyl ester;(o) (2S,4R)-5-biphenyl-4-yl-2-hydroxymethyl ...

RESOLUTION METHOD FOR AXIS CHIRAL ENANTIOMERS OF LESINURAD

A resolution method of axial chiral enantiomers of lesinurad (2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid) adopts inexpensive and readily available quinoline natural products and derivatives thereof, such as quinine, cinchonine, quinidine or cinconidine as resolving agents to react with lesinurad racemate in an organic solvent to form a salt, and the salt is dissociated by acidification so as to obtain optically pure (R)- or (S)-2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid. The method can give axial chiral enantiomer of lesinurad in R configuration with a chiral purity ee of up to 100% and a total yield of 90% or more. The obtained axial chiral enantiomer of lesinurad in S configuration can reach a chiral purity ee of up to 99.9% and a total yield of 80% or more. 1. A resolution method of axial chiral enantiomers of lesinurad , comprising:(1) reacting axial chiral lesinurad racemate with resolving agent 1 in a solvent, and after filtration, subjecting the obtained solid to acid hydrolysis to give compound 1 after concentration;(2) concentrating the mother liquor obtained by the filtration in step (1), and subjecting the obtained solid to acid hydrolysis to give compound 2 after concentration;wherein, the resolving agent 1 is quinine (CAS:130-95-0), quinidine (CAS:56-54-2), cinchonidine (CAS:485-71-2) or cinchonine (CAS:118-10-5).2. The method according to claim 1 , wherein the solvent used in the reaction or acid hydrolysis in step (1) and that used in the acid hydrolysis in step (2) are the same or different claim 1 , and are independently one claim 1 , two or more selected from the group consisting of ester solvents claim 1 , alcohol solvents claim 1 , ketone solvents claim 1 , ether solvents claim 1 , and aromatic hydrocarbon solvents.3. The method according to claim 1 , wherein the pH values of the acid hydrolysis in step (1) and step (2) are the same or different claim 1 , and are ...

COMPOUNDS, COMPOSITIONS AND METHODS OF USING SAME FOR MODULATING URIC ACID LEVELS

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid. 137.-. (canceled)39. The compound of claim 38 , wherein W is S.40. The compound of claim 38 , wherein Ris Br.41. The compound of claim 38 , whereinW is S; and{'sup': '1', 'Ris Br.'}42. The compound of claim 38 , whereina is 1;{'sup': 'a', 'Ris H; and'}{'sup': 'a′', 'Ris H.'}43. The compound of claim 38 , wherein A is C(O)O—B.44. The compound of claim 38 , wherein{'sup': '1', 'A is C(O)O—B;'}x is 1; and{'sup': x', 'x′, 'Rand Rare not H.'}45. The compound of claim 38 , wherein Rand Rtogether with the carbon atoms to which they are attached claim 38 , form an optionally substituted claim 38 , non-aromatic 3 membered ring.46. The compound of claim 38 , wherein R claim 38 , R claim 38 , Rand Rare all H.47. The compound of claim 38 , wherein Rand Rtogether with the two carbon atoms to which they are attached claim 38 , form an aromatic claim 38 , 6-membered ring.48. A method of treating gout in an individual claim 38 , the method comprising administering to the individual a therapeutically effective amount of a compound of .49. A method of treating hyperuricemia in an individual or reducing serum uric acid in an individual in need thereof claim 38 , the method comprising administering to the individual a therapeutically effective amount of a compound of .50. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 38 , and a pharmaceutically acceptable excipient. This application claims the benefit of U.S. Provisional Application No. 61/094,388, filed Sep. 4, 2008, U.S. Provisional Application No. 61/180,110, filed May 20, 2009, and U.S. application Ser. No. 12/324,764, filed Nov. 26, 2008; each of which are incorporated herein by reference ...

METHOD FOR TREATING INFLAMMATORY DISORDERS

The present invention relates to a method for suppressing the immune system in a subject in need thereof, and a method for treating an inflammatory or immune disorder in a subject in need thereof. 362-. (canceled) This application claims the benefit of U.S. Provisional Application No. 60/854,675, filed Oct. 26, 2006, the entire teachings of which are incorporated herein by reference.The invention relates to a method of modulating glucocorticoid receptors in a subject and methods for immunosuppression and for treating inflammatory and autoimmune disorders. In addition, the invention relates to a method for a method for monitoring the treatment of a patient with an Hsp90 inhibitor, and a method for optimizing dosing for a subject undergoing cancer therapy with an Hsp90 inhibitor.Heat shock proteins (HSPs) are a class of chaperone proteins that are up-regulated in response to elevated temperature and other environmental stresses, such as ultraviolet light, nutrient deprivation, and oxygen deprivation. HSPs act as chaperones to other cellular proteins (called client proteins) and facilitate their proper folding and repair, and aid in the refolding of misfolded client proteins. There are several known families of HSPs, each having its own set of client proteins. The Hsp90 family is one of the most abundant HSP families, accounting for about 1-2% of proteins in a cell that is not under stress and increasing to about 4-6% in a cell under stress. Inhibition of Hsp90 results in degradation of its client proteins via the ubiquitin proteasome pathway.Steroidal glucocorticoids are commonly used to treat a variety of inflammatory disorders due to their powerful anti-inflammatory effects. Glucocorticoid receptors (GR) assemble into a multiprotein complex in the cytoplasm in which Hsp90 is required to maintain the receptor in a conformation capable of binding glucocorticoid with high affinity. In humans, the main glucocorticoid is cortisol which binds to the GR complex in the ...

METHOD OF TREATING CANCER WITH MODULATORS OF SCFSkp2

The present invention relates to pharmaceutical compositions comprising a compound and a pharmaceutically acceptable carrier. The present invention is also directed to a method of treating cancer in a subject. Also disclosed are methods of inhibiting SCF-Skp2 activity and a method of identifying inhibitors of SCF-Skp2 activity. 2. The pharmaceutical composition of claim 1 , wherein R is selected from the group consisting of CHR claim 1 , CHC(O)R claim 1 , or CHC(O)NHR.3. The pharmaceutical composition of claim 2 , wherein Ris unsubstituted or substituted with a halogen.4. The pharmaceutical composition of claim 1 , wherein Y is S.8. The pharmaceutical composition of claim 7 , wherein L claim 7 , L claim 7 , and Lare absent.10. The pharmaceutical composition of claim 7 , wherein A claim 7 , B claim 7 , G claim 7 , and W are C.11. The pharmaceutical composition of claim 7 , wherein Land Lare absent.18. The method according to claim 17 , wherein the cancer is selected from the group consisting of multiple myeloma claim 17 , lymphoma claim 17 , melanoma claim 17 , leukemia claim 17 , sarcoma claim 17 , glioblastoma claim 17 , nasopharyngeal carcinoma claim 17 , stomach (gastric) cancer claim 17 , renal cancer claim 17 , ovarian cancer claim 17 , oral cancer claim 17 , cancers of the pancreas claim 17 , prostate claim 17 , colon claim 17 , lung claim 17 , liver claim 17 , thyroid claim 17 , and biliary tract claim 17 , and endometrial cancers.19. The method of claim 17 , wherein the compound of formula I is administered and wherein R is selected from the group consisting of CHR claim 17 , CHC(O)R claim 17 , or CHC(O)NHR.20. The method of claim 19 , wherein the compound of formula I is administered and wherein Ris unsubstituted or substituted with a halogen.21. The method of claim 17 , wherein the compound of formula I is administered and wherein Y is S.24. The method of claim 17 , wherein the compound of formula II is administered and wherein L claim 17 , L claim 17 , ...

NOVEL TRIAZOLONE DERIVATIVES OR SALTS THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

Provided is a triazolone derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The triazolone derivative or its pharmaceutically acceptable salt can effectively activate GPR119; and therefore be usefully applied for preventing or treating diabetes mellitus. 3. The compound or its pharmaceutically acceptable salt of claim 2 , wherein{'sub': 6', '7', '1', '6', '1', '6', '1', '6', '1', '6, 'Rand Ris, independently each other, hydrogen; a C˜Calkyl group; a C˜Calkylcarbonyl group; a C˜Calkoxycarbonyl group; or a C˜Calkylsulfonyl group, and'}{'sub': 8', '1', '6, 'Ris be a C˜Calkoxy group, an amino group, or a 3- to 12-membered heterocyclic group.'}5. The compound or its pharmaceutically acceptable salt of claim 4 , wherein Rand Ris cyclized each other to form a piperazinyl group or a piperidinyl group.7. The compound or its pharmaceutically acceptable salt of claim 6 , wherein{'sub': 9', '1', '6, 'Ris a C˜Calkyl group,'}{'sub': 10', '1', '6', '2', '6, 'Ris a C˜Calkyl group or a C˜Calkenyl group,'}{'sub': 11', '1', '6, 'Ris a C˜Calkyl group,'}{'sub': 12', '1', '6', '1', '6, 'Ris a C˜Calkylsulfonyl group or a 5- to 12-membered heteroaryl group optionally substituted with C˜Calkyl, and'}{'sub': 13', '1', '6, 'Ris a C˜Calkyl group.'}8. The compound or its pharmaceutically acceptable salt of claim 1 , wherein Rand Ris claim 1 , independently each other claim 1 , hydrogen; a halogen group; a cyano group; or a C˜Calkyl group optionally substituted with one or more halogens.9. The compound or its pharmaceutically acceptable salt of claim 1 , wherein X and P is claim 1 , independently each other claim 1 , N or CR; and Ris hydrogen or a halogen group.10. The compound or its pharmaceutically acceptable salt of claim 1 , wherein Y is CR; and Ris hydrogen or a halogen group.11. The compound or its pharmaceutically acceptable salt of claim 1 , which is selected from the group consisting of:(S)- ...

NOVEL PREPARATION METHOD FOR ANTI-GOUT DRUG LESINURAD, AND KEY INTERMEDIATE THEREOF

A novel preparation method for the anti-gout drug Lesinurad, and a key intermediate thereof. The method comprises the following reaction steps: 1) the compound of formula II undergoing a substitution reaction with R—SH in the presence of a first solvent and a first alkali to generate a mixture containing the compound of formula III and the compound of formula IV; 2) adding a second alkali and RX to the resulting mixture for a reaction to obtain the compound of formula III, wherein: R represents a cyclopropane group, a halogen, a triflate group, a mesylate group or a tosylate group, preferably a cyclopropane group; Rrepresents —COCH, a benzyl group or —CHR, wherein Rrepresents a methyl acetate group, an ethyl acetate group, —C(O)OCH, —C(O)OCH, —CN, —CHOH or a phenyl group substituted with one or more of a C1-C6 alkyl group and a halogen; X represents a halogen. The process of the present invention directly converts the compound of formula IV into the product compound of formula III without separation, significantly increasing the reaction yield and simplifying the operation steps. In addition, the synthesis of the new intermediate of the present invention does not require the use of highly toxic thiophosgene and carbon disulphide, significantly improving the safety and environmental friendliness of the process. 2. The preparation method according to claim 1 , wherein the first solvent is selected from the group consisting of N claim 1 ,N-dimethylformamide claim 1 , N-methylpyrrolidone and acetonitrile claim 1 , or any combination thereof; the first base in the step 1) and the second base in the step 2) are independently selected from the group consisting of 1 claim 1 ,8-diazabicycloundec-7-ene claim 1 , diisopropylethylamine claim 1 , triethylamine claim 1 , potassium carbonate and sodium carbonate claim 1 , or any combination thereof.3. The preparation method according to claim 1 , wherein the mixture obtained in the step 1) is subjected to a next reaction directly ...

1, 2, 4-TRIAZOLE DERIVATIVES AND THEIR ANTI-MICROBIAL ACTIVITY

Triazole derivatives useful as anti-tubercular compounds; process for preparation of the triazoles and a method for inhibiting growth of BCG and H37Ra using the triazoles. 2. A compound of selected from the group consisting of:3-(allylthio)-5-(4-methoxyphenyl)-1H-1,2,4-triazole,3-(allylthio)-5-(4-chlorophenyl)-1H-1,2,4-triazole,1-allyl-3-(allylthio)-1H-1,2,4-triazole,1-allyl-3-(allylthio)-5-(4-methoxyphenyl)-1H-1,2,4-triazole,1-allyl-3-(allylthio)-5-(4-chlorophenyl)-1H-1,2,4-triazole, and1-allyl-5-(allylthio)-3-(4-methoxyphenyl)-1H-1,2,4-triazole.3. A compound of selected from the group consisting of:5-(prop-2-ynylsulfonyl)-1H-1,2,4-triazole,3-tert-butyl-5-(prop-2-ynylsulfonyl)-1H-1,2,4-triazole,3-(4-nitrophenyl)-5-(prop-2-ynylsulfonyl)-1H-1,2,4-triazole,3-(4-methoxyphenyl)-5-(prop-2-ynylsulfonyl)-1H-1,2,4-triazole and3-(4-chlorophenyl)-5-(prop-2-ynylsulfonyl)-1H-1,2,4-triazole.4. A compound of selected from the group consisting of:1-allyl-3-tert-butyl-5-(prop-2-ynylthio)-1H-1,2,4-triazole and1-allyl-5-tert-butyl-3-(prop-2-ynylthio)-1H-1,2,4-triazole.5. A compound of selected from the group consisting of:5-(allylthio)-3-tert-butyl-1-(prop-2-ynyl)-1H-1,2,4-triazole,3-(allylthio)-5-tert-butyl-1-(prop-2-ynyl)-1H-1,2,4-triazole,1-allyl-5-(prop-2-ynylthio)-1H-1,2,4-triazole,1-allyl-3-(prop-2-ynylthio)-1H-1,2,4-triazole, and1-allyl-5-methyl-3-(prop-2-ynylthio)-1H-1,2,4-triazole.6. A compound of selected from the group consisting of: 1-Benzyl-4-((1-((1-benzyl)-1H-1 claim 1 ,2 claim 1 ,3-triazol-4-yl)methyl)-5-tert-butyl-1H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)methyl)-1H-1 claim 1 ,2 claim 1 ,3-triazole and 1-benzyl-4-((1-((1-benzyl-1H-1 claim 1 ,2 claim 1 ,3-triazol-4-yl)methyl)-3-tert-butyl-1H-1 claim 1 ,2 claim 1 ,4-triazol-5-ylthio)methyl)-1H-1 claim 1 ,2 claim 1 ,3-triazole.7. A compound of selected from the group consisting of: 4-benzyl-1-[(1H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)methyl]-1H-1 claim 1 ,2 claim 1 ,3-triazole claim 1 , 4-benzyl-1-{[(5-methyl-1H-1 ...

Reagents and Methods for Analysis of Proteins and Metabolites Targeted by Covalent Probes

The present application relates to mass spectrometry methods for use in identifying proteins or other biomolecules which are bound irreversibly by test compounds. 1. An analytical method , comprising:i) contacting a broad thiol reactive compound with a polypeptide to form a broad thiol reactive compound-polypeptide conjugate;ii) analyzing the broad thiol reactive compound-polypeptide conjugate using a mass spectrometry assay;iii) detecting one or more thiolated ions of the broad thiol reactive compound, or derivative ions thereof, produced in the mass spectrometry assay; andiv) identifying that the broad thiol reactive compound forms an irreversible bond with the polypeptide based on the detection of the one or more thiolated ions, or derivative ions thereof, in the mass spectrometry assay;wherein the thiolated ions or derivatives thereof are fragment ions.2. The method of claim 1 , wherein the compound-polypeptide conjugate comprises one or more thioether bonds between the compound and the polypeptide.3. The method of claim 1 , wherein the irreversible bond is an irreversible covalent bond.4. The method of claim 1 , wherein step i) comprises contacting the compound and the polypeptide in the presence of a first solvent component.5. The method of claim 1 , wherein step i) further comprises contacting the compound and the polypeptide in the presence of a buffer agent.6. The method of claim 1 , wherein step i) is performed using a molar excess of the compound compared to the polypeptide.7. The method of claim 1 , further comprising contacting the broad thiol reactive compound-polypeptide conjugate with an acid in the presence of a second solvent component prior to performing the mass spectrometry assay of step ii).8. The method of claim 1 , wherein the method further comprises digesting the broad thiol reactive compound-polypeptide conjugate prior to the performing the mass spectrometry assay of step ii).9. The method of claim 8 , wherein the digesting comprises ...

PROCESS FOR PREPARATION OF FUNGICIDALLY ACTIVE TRIAZOLE COMPOUNDS

The present invention relates to a process for the preparation of fungicidally active triazole compounds wherein said process uses homologous cage amines as the catalyst. 2. The process of claim 1 , wherein said 1 claim 1 ,2 claim 1 ,4-triazole fungicide is prothioconazole claim 1 , azaconazole claim 1 , bromuconazole claim 1 , cyproconazole claim 1 , difenoconazole claim 1 , hexaconazole claim 1 , fenbuconazole claim 1 , ipconazole claim 1 , metconazole claim 1 , epoxiconazole claim 1 , etaconazole claim 1 , penconazole claim 1 , propiconazole claim 1 , tebuconazole claim 1 , simeconazole claim 1 , tetraconazole claim 1 , myclobutanil claim 1 , ipfentrifluconazole claim 1 , mefentrifluconazole claim 1 , diclobutrazol claim 1 , triadimefon am triadimenol.3. A process of claim 1 , wherein said 1 claim 1 ,2 claim 1 ,4-triazole fungicide is prothioconazole.4. The process of claim 1 , wherein said homologous cage amine catalyst is selected from 1 claim 1 ,4-diazabicyclo[2.2.2]octane claim 1 , 1-azabicyclo[2.2.2]octane claim 1 , azabicyclo(5.2.2)undecanes claim 1 , azabicyclo(3.3.1)nonanes claim 1 , azabicyclo(4.3.0)nonanes claim 1 , azabicyclo(1.1.0)butanes claim 1 , azabicyclo(2.2.2)octanes and N-methyl-8-azabicyclo[3.2.1]octane claim 1 , 1 claim 1 ,5-diazabicyclo[4.3.0]non-5-ene claim 1 , 1 claim 1 ,8-diazabicyclo[5.4.0]undec-7-ene claim 1 , and 1 claim 1 ,3 claim 1 ,6 claim 1 ,8-tetraazatricyclo[4.3.1.13 claim 1 ,8] undecane.5. The process of claim 1 , wherein said process is carried out in the presence of between 0.01 mol % and 20 mol % of said homologous cage amine catalyst.6. The process of claim 1 , wherein said process is carried out in the presence of between 0.05 mol % and 10 mol % of said homologous cage amine catalyst.7. The process of claim 1 , whereinsaid homologous cage amine catalyst is selected from 1-azabicyclo[2.2.2]octane and 1,4-diazabicyclo[2.2.2]octane.8. A process for the preparation of 2-(1-chloro-cyclopropyl)-1-(2-chlorophenyl)-3-(5-mercapto-1 ...

Triazoles as kv3 inhibitors

Compounds of formula (I) are of use in the modulation of Kv3.1, Kv.3.2 and Kv3.3 channels and have utility in the treatment or prevention of related disorders.

TRIAZOLONE COMPOUNDS AND USES THEREOF

The invention disclosed herein is directed to compounds of Formula (I) and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention also comprises pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula (I), or a pharmaceutically acceptable salt thereof. The invention disclosed herein is also directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention disclosed herein is further directed to methods of treating prostate, breast, colon, pancreatic, chronic lymphocytic leukemia, melanoma and other cancers comprising administration of a of a therapeutically effective amount of a selective PPARα antagonist. The compounds and pharmaceutical compositions of the invention are also useful in the treatment of viral infections, such as HCV infections and HIV infections. The invention disclosed herein is also directed to a methods of preventing the onset of and/or recurrence of acute and chronic myeloid leukemia, as well as other cancers, comprising administration of a of a therapeutically effective amount of a selective PPARα antagonist. 23-. (canceled)4. The compound according claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sub': 2', '2', '2, 'X is —CHCHCH—.'}5. The compound according claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:A1 is a substituted phenyl or substituted pyridine.6. The compound according claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:A2 is A2a.7. The compound according claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein:A2a is a substituted phenyl or substituted pyridine.8. The compound according claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:Y ...

CRYSTAL AND SALT OF 4-(NAPHTHALEN-1-YL)-4H-1,2,4-TRIAZOLE COMPOUND AND PREPARATION METHOD THEREFOR

Disclosed are a crystal of a 4-(naphthalene-1-yl)-4H-1,2,4-triazole compound (1) and a preparation method therefor, also comprised are applications of the crystal in preparing a medicament for treating an abnormal uric acid level-related disease. 2. The crystal form A claim 1 , crystal form D or amorphous form I of compound 1 as defined in claim 1 , wherein the crystal form A of compound 1 has an X-ray powder diffraction pattern comprising characteristic diffraction peaks at angle 2θ of 7.16±0.2° claim 1 , 12.50±0.2° claim 1 , 14.61±0.2° claim 1 , 17.98±0.2° claim 1 , 19.62±0.2° claim 1 , 22.30±0.2° claim 1 , 24.63±0.2° claim 1 , and 26.37±0.2°;and/or, the crystal form D of compound 1 has an X-ray powder diffraction pattern thereof comprising characteristic diffraction peaks at angle 2θ of 9.19±0.2°, 10.87±0.2°, 11.63±0.2°, 13.72±0.2°, 14.41±0.2°, 16.90±0.2°, 19.95±0.2°, and 22.22±0.2°.3. The crystal form A claim 2 , crystal form D or amorphous form I of compound 1 as defined in claim 2 , wherein the crystal form A of compound 1 has an X-ray powder diffraction pattern comprising characteristic diffraction peaks at angle 2θ of 7.16±0.2° claim 2 , 9.56±0.2° claim 2 , 11.30±0.2° claim 2 , 12.50±0.2° claim 2 , 14.61±0.2° claim 2 , 17.98±0.2° claim 2 , 18.72±0.2° claim 2 , 19.62±0.2° claim 2 , 22.30±0.2° claim 2 , 24.63±0.2° claim 2 , and 26.37±0.2°;and/or, the crystal form D of compound 1 has an X-ray powder diffraction pattern comprising characteristic diffraction peaks at angle 2θ of 9.19±0.2°, 10.87±0.2°, 11.63±0.2°, 13.72±0.2°, 14.41±0.2°, 16.90±0.2°, 19.95±0.2°, 22.22±0.2°, and 26.11±0.2°.4. The crystal form A claim 3 , crystal form D or amorphous form I of compound 1 as defined in claim 3 , wherein the crystal form A of compound 1 has an X-ray powder diffraction pattern as shown in ;{'figref': {'@idref': 'DRAWINGS', 'FIG. 19'}, 'and/or, the crystal form D of compound 1 has an X-ray powder diffraction pattern as shown in .'}5. The crystal form A claim 1 , crystal ...

Nrf2 Activating Compounds and Uses Thereof

Aspects of the present disclosure include compounds that activate Nrf2. Such compounds find use in the treatment of autoimmune and inflammatory diseases and disorders, such as for example psoriasis and multiple sclerosis. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes. 120.-. (canceled)22. The method of claim 21 , wherein the disease or disorder is cardiac insufficiency.23. The method of claim 22 , wherein the cardiac insufficiency is selected from the group consisting of left ventricular insufficiency claim 22 , myocardial infarction claim 22 , and angina pectoris.24. The method of claim 21 , wherein the disease or disorder is asthma.25. The method of claim 21 , wherein the disease or disorder is arthritis.26. The method of claim 25 , wherein the arthritis is selected from the group consisting of inflammatory arthritis claim 25 , rheumatoid arthritis claim 25 , juvenile rheumatoid arthritis (juvenile idiopathic arthritis) claim 25 , psoriatic arthritis claim 25 , and ankylosing spondylitis.27. The method of claim 21 , wherein the disease or disorder is an inflammatory bowel disease.28. The method of claim 27 , wherein the inflammatory bowel disease is selected from the group consisting of Crohn's disease and ulcerative colitis.29. The method of claim 27 , wherein the inflammatory bowel disease is Crohn's disease.30. The method of claim 21 , wherein the disease or disorder is a chronic obstructive pulmonary disease.31. The method of claim 30 , wherein the chronic obstructive pulmonary disease is selected from the group consisting of bronchitis and emphysema.33. The method of claim 21 , wherein the sulfonyl is selected from alkyl-SO— claim 21 , substituted alkyl-SO— claim 21 , alkenyl-SO— claim 21 , substituted alkenyl-SO— claim 21 , ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 128-. (canceled)30. The method of claim 29 , wherein the disease is selected from hypertension claim 29 , heart failure claim 29 , and renal disease.31. The method of claim 29 , further comprising administering a therapeutic agent selected from an ATreceptor antagonist claim 29 , an angiotensin-converting enzyme inhibitor claim 29 , a phosphodiesterase inhibitor claim 29 , a renin inhibitor claim 29 , and a diuretic claim 29 , or a combination thereof.32. The method of claim 29 , further comprising administering an ATreceptor antagonist claim 29 , wherein the ATreceptor antagonist is selected from abitesartan claim 29 , azilsartan claim 29 , azilsartan medoxomil claim 29 , benzyllosartan claim 29 , candesartan claim 29 , candesartan cilexetil claim 29 , elisartan claim 29 , embusartan claim 29 , enoltasosartan claim 29 , eprosartan claim 29 , EXP3174 claim 29 , fonsartan claim 29 , forasartan claim 29 , glycyllosartan claim 29 , irbesartan claim 29 , isoteoline claim 29 , losartan claim 29 , milfasartan claim 29 , olmesartan claim 29 , olmesartan medoxomil claim 29 , opomisartan claim 29 , pratosartan claim 29 , ripisartan claim 29 , saprisartan claim 29 , saralasin claim 29 , sarmesin claim 29 , TAK-591 claim 29 , tasosartan claim 29 , telmisartan claim 29 , valsartan claim 29 , and zolasartan.33. The method of claim 29 , wherein Ris —OR; and Ris selected from H and —Calkyl.34. The method of claim 29 , wherein Ris H.35. The method of claim 29 , wherein X is selected from oxazole and isoxazole.36. The method of claim 29 , wherein Ris selected from H claim 29 , —Calkylene-OH claim 29 , —Calkyl claim 29 , and —Calkylene-O—Calkyl; and Ris H.37. The method of claim 29 , wherein a is 0; b is 0 claim 29 , 1 or 2; and each Ris independently selected from halo.38. The method of claim 29 , wherein Ris —OR; Ris selected from H and —Calkyl; Ris H; X is selected from oxazole and isoxazole; Ris selected from H ...

Compositions for Inhibition of Insect Sensing

In one aspect, the invention relates to chemical modulators of insect olfactory receptors. In particular, compounds and compositions are provided that can inhibit sensory (e.g., host targeting) functions in airborne insects such as mosquitoes. Methods of employing such agents, and articles incorporating the same, are also provided. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 4. The formulation of claim 3 , wherein Ris hydrogen claim 3 , or Ris taken together with Rto be optionally substituted (C1-C4) alkanediyl or optionally substituted (C1-C4) alkenediyl; wherein Ris optionally substituted (C1-C5) alkyl or optionally substituted (C1-C5) alkenyl; and wherein Ris optionally substituted and selected from (C1-C5) alkyl and (C1-C5) alkenyl.5. The formulation of claim 3 , wherein R′ claim 3 , R claim 3 , and Rare hydrogen; wherein Ris (C1-C5) alkyl; and wherein Ris optionally substituted (≤C6) heteroaryl.7. The formulation of claim 6 , wherein Ris hydrogen; wherein Ris hydrogen; wherein Ris methyl claim 6 , ethyl claim 6 , n-propyl claim 6 , or isopropyl; wherein Ris ethyl claim 6 , propyl claim 6 , or cyclopropyl; and wherein Ris hydrogen claim 6 , hydroxy claim 6 , —F claim 6 , —CI claim 6 , —Br claim 6 , —I claim 6 , —NH claim 6 , or —NO.9. The formulation of claim 8 , wherein Ris hydrogen; wherein Ris hydrogen; wherein Ris methyl claim 8 , ethyl claim 8 , n-propyl claim 8 , or isopropyl; and wherein Ris hydrogen claim 8 , hydroxy claim 8 , —F claim 8 , —CI claim 8 , —Br claim 8 , —I claim 8 , —NH claim 8 , or —NO.12. The formulation of claim 11 , wherein Ris hydrogen; wherein Ris hydrogen; and{'sup': '3', 'wherein Ris methyl, n-propyl, or isopropyl.'} This application is a continuation of U.S. application Ser. No. 15/443,340, filed on Feb. 27, 2017, which is a continuation of U.S. application Ser. No. 14/115,553, filed on May 2, 2014 (now U.S. Pat. No. 9,578, ...

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR AGONISTS

Disclosed herein, inter alia, are compositions and methods useful for treating liver diseases and metabolic diseases. 3. The compound of one of to , wherein Lis substituted or unsubstituted C-Calkylene.4. The compound of one of to , wherein Lis substituted or unsubstituted C-Calkylene.5. The compound of one of to , wherein Lis —C(CH)—.6. The compound of one of to , wherein Lis unsubstituted C-Calkylene.7. The compound of one of to , wherein Lis unsubstituted n-propylene.8. The compound of one of to , wherein Lis a bond or substituted or unsubstituted alkylene.9. The compound of one of to , wherein Lis a bond or unsubstituted C-Calkylene.10. The compound of one of to , wherein Lis an unsubstituted C-Calkylene.11. The compound of one of to , wherein Lis an unsubstituted methylene.12. The compound of one of to , wherein Ris substituted or unsubstituted C-Ccycloalkyl , substituted or unsubstituted 4 to 6 membered heterocycloalkyl , substituted or unsubstituted phenyl , or substituted or unsubstituted 5 to 6 membered heteroaryl.13. The compound of one of to , wherein Ris substituted or unsubstituted phenyl or substituted or unsubstituted 5 to 6 membered heteroaryl.14. The compound of one of to , wherein Ris substituted or unsubstituted phenyl.15. The compound of one of to , wherein Ris R-substituted or unsubstituted phenyl or R-substituted or unsubstituted 5 to 6 membered heteroaryl;{'sup': 2', '2', '2', '2', '2', '2', '2', '2A', '2A', '2B', '2C', '2A', '2B', '2A', '2B', '2C', '2A', '2B', '2A', '2A', '2A', '2B', '2C', '2A', '2B', '2A', '2A', '2B', '2A', '2B', '2A', '2B', '2A', '2B, 'sub': 3', '2', '2', '3', '2', '2', 'n2', 'v2', 'm2', '2', '3, 'Ris independently halogen, —CX, —CHX, —CHX, —OCX, —OCHX, —OCHX, —CN, —SOR, —SONRR, —NRC(O)NRR, —N(O), —NRR, NRNRR, —C(O)R, —C(O)OR, —C(O)NRR, —C(O)NRNRR, —OR, —NRSOR, —NRC(O)R, —NRC(O)OR, —NROR, —N, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or ...

AXIALLY CHIRAL ISOMERS, AND PREPARATION METHODS THEREFOR AND PHARMACEUTICAL USES THEREOF

Disclosed are two axially chiral isomers and pharmaceutically available salts thereof, preparation method therefor, and pharmaceutical use of the two axially chiral isomers or pharmaceutical compositions thereof. 6. The process according to claim 3 , whereinthe hydrolysis is carried out under strong base conditions; wherein the strong base is LiOH, NaOH, or KOH.8. The process according to claim 5 , wherein claim 5 , the brominating reagent is Br/base; wherein the base is selected from pyridine claim 5 , triethylamine claim 5 , or DIPEA.9. The process according to claim 5 , wherein claim 5 , the sulfonate is selected from the group consisting of mesylate claim 5 , p-toluenesulfonate claim 5 , p-nitrobenzenesulfonate and trifluoromethanesulfonate.10. A pharmaceutical composition comprising a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to claim 1 , as an active ingredient and a pharmaceutically acceptable carrier.11. A process for treating a patient in need of a medicament for a condition associated with abnormal serum uric acid level claim 1 , comprising administering to the patient an effective amount of a compound or a pharmaceutically acceptable salt thereof according to .12. The process according to claim 3 , wherein W is Calkyl or said Calkyl substituted by 1 or 2 or 3 of halogen claim 3 , OH claim 3 , CN and NH.14. The process according to claim 4 , wherein the hydrolysis is carried out under strong base conditions wherein the strong base is selected from the group consisting of LiOH claim 4 , NaOH claim 4 , and KOH.15. The process according to claim 5 , wherein the hydrolysis is carried out under strong base conditions wherein the strong base is selected from the group consisting of LiOH claim 5 , NaOH claim 5 , and KOH.18. A pharmaceutical composition comprising a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to claim 2 , as an active ingredient ...

TRIAZOLONE COMPOUNDS AS mPGES-1 INHIBITORS

The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases. 147-. (canceled)49. The compound according to claim 48 , wherein X claim 48 , X claim 48 , Xand Xare CH.50. The compound according to claim 48 , wherein each occurrence of Ris independently cyano claim 48 , Cl claim 48 , F claim 48 , CHF claim 48 , CF claim 48 , OCH claim 48 , CH claim 48 , (2 claim 48 ,2 claim 48 ,2-trifluoroethoxy)methyl claim 48 , cyclopropyl claim 48 , (pyrrolidin-1-yl)methyl claim 48 , 4-methylthiophenyl claim 48 , 5-isopropyl-1 claim 48 ,3 claim 48 ,4-oxadiazol-2-yl claim 48 , (3 claim 48 ,5-dimethyl-1H-pyrazol-1-yl)methyl claim 48 , 3 claim 48 ,3-dimethylbut-1-ynyl claim 48 , 2-cyclopropylethynyl claim 48 , (2 claim 48 ,5-dichlorophenyl)ethynyl claim 48 , (4-chloro-2-fluorophenyl)ethynyl claim 48 , (3-chloro-2-fluorophenyl)ethynyl claim 48 , (3-(trifluoromethyl)phenyl)ethynyl or (2-chloro-4-(trifluoromethyl)phenyl)ethynyl; and ‘n’ is 1 or 2.51. The compound according to claim 48 , wherein each occurrence of Ris independently cyano claim 48 , Cl claim 48 , F claim 48 , CH claim 48 , CF claim 48 , OCH claim 48 , 3-(4-chlorophenyl)-1 claim 48 ,2 claim 48 ,4-oxadiazol-5-yl claim 48 , cyclopropanecarboxamido claim 48 , 3 claim 48 ,3-dimethylbut-1-ynyl claim 48 , 2-cyclopropylethynyl claim 48 , —CONH-[3-(trifluoromethyl)phenyl] claim 48 , —CONH-[3-(difluoromethyl)-4-fluorophenyl] or —CONH-[3-(difluoromethyl)phenyl]; and ‘m’ is 1 or 2.52. The compound according to claim 48 , wherein Q is isopropyl claim 48 , tert-butyl claim 48 , trifluoromethyl claim 48 , 1-fluoro-2-methylpropan-2-yl claim 48 , 1-methoxy-2- ...

METHOD FOR PREPARING AMINO-TRIAZOLINONE

The present invention relates to a method for preparing an amino-triazolinone which can be used as a raw material for amicarbazone and has chemical formula (I). The method for preparing the amino-triazolinone includes the steps of: reacting an acyl hydrazide of chemical formula (II) with a carbamating agent of chemical formula (III) or (IV) so as to obtain a hydrazine carboxylic acid of chemical formula (V); and reacting the thus-obtained hydrazine carboxylic acid of chemical formula (V) with a hydrazine hydrate under the presence of a base catalyst. According to the present invention, the amino-triazolinone may be stably prepared without using safety equipment or safety facilities for a possible leakage of phosgene, which has been used as a conventional reactant. Thus, manufacturing costs for amicarbazone, which is used as a herbicide for farm products such as sugar cane, corn, or the like, can be reduced so as to achieve improved price competitiveness, and further to achieve improved cost competitiveness compared to other herbicides. 2. The method of claim 1 , wherein the carbamating agent of Chemical Formula III or IV is any one selected from a group consisting of methyl chloroformate claim 1 , ethyl chloroformate claim 1 , isopropyl chloroformate claim 1 , dimethyl carbonate claim 1 , diethyl carbonate.3. The method of claim 1 , wherein the base catalyst is any one selected form a group consisting of NaOH claim 1 , KOH claim 1 , NaHCO claim 1 , NaCO claim 1 , KHCO claim 1 , KCO claim 1 , CaCO.4. The method of claim 1 , wherein the carbamating agent of Chemical Formula III used in step (1) above is methyl chloroformate (MCF) claim 1 , and a solvent used in step (1) above is selected from methylene chloride (MC) claim 1 , methanol and toluene and a reaction temperature used in step (1) above is 10 to 25° C.5. The method of claim 4 , wherein the base catalyst used in step (2) above is NaOH or KOH.6. The method of claim 4 , wherein a solvent used in step (2) above ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula X: 124-. (canceled)25. A compound of:(a) (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[1-(3-chlorophenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl]hydrazino}-2-hydroxypropionic acid;(b) (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[1-(3-chlorophenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl]hydrazino}-2-hydroxypropionic acid ethyl ester;(c) (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[1-(3-chlorophenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl]hydrazino}-2-hydroxypropionic acid isobutyl ester;(d) (S)-2-amino-3-methylbutyric Acid (R)-3-{N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[1-(3-chlorophenyl)-5-hydroxy-1H-[1,2,4]triazole-3-carbonyl]hydrazino}-2-hydroxypropionyloxymethyl ester;(e) (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[1-(3-chlorophenyl)-5-hydroxy-1H-[1,2,4]triazole-3-carbonyl]hydrazino}-2-hydroxypropionic acid acetoxymethyl ester;(f) (S)-2-amino-3-methylbutyric Acid 5-[N′4(R)-2-Carboxy-2-hydroxyethyl)-N′-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazinocarbonyl]-2-(3-chlorophenyl)-2H-[1,2,4]triazol-3-yloxymethyl ester; or(g) (R)-3-[N′-[5-acetoxymethoxy-1-(3-chlorophenyl)-1H-[1,2,4]triazole-3-carbonyl]-N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid.26. A compound of:(a) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(2-hydroxythiazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid; or(b) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(2-hydroxythiazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid ethyl ester.27. A compound of:(a) (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid;(b) (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid isobutyl ester;(c) (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[3-(2-fluorophenyl)isoxazole-5- ...

S-TRIAZOLYL ALPHA-MERCAPTO ACETANILIDES AS INHIBITORS OF HIV REVERSE TRANSCRIPTASE

A series of S-triazolyl α-mercaptoacetanilides having general structure (1) are provided, where Q is COH, CONR, SOH, or SONR. The compounds inhibit several variants of the reverse transcriptase of HIV, and are useful in the treatment of HIV infections. 2. The compound of claim 1 , wherein none of R claim 1 , R claim 1 , and Rare OH claim 1 , NHor NHCH.3. The compound of claim 1 , wherein P is not substituted phenyl and at least one of R claim 1 , R claim 1 , and Ris other than H or CH.4. The compound of claim 1 , wherein P is a substituted phenyl and Ris not methyl.5. The compound of claim 2 , wherein P is not substituted phenyl and at least one of R claim 2 , R claim 2 , and Ris other than H or CH.6. The compound of claim 3 , wherein P is not substituted phenyl and at least one of R claim 3 , R claim 3 , and Ris other than H or CH.7. The compound of claim 2 , wherein P is a substituted naphthyl and Ris selected from the group consisting of Br claim 2 , CF claim 2 , CFH claim 2 , and CFH.8. The compound of claim 7 , wherein each of R claim 7 , R claim 7 , and Ris H.9. The compound of claim 7 , wherein Ris cyclopropyl.10. The compound of claim 7 , wherein Ris Br and Ris Cl.11. The compound of claim 2 , wherein P is a substituted quinoline or isoquinoline and Ris selected from the group consisting of Br claim 2 , CF claim 2 , CFH claim 2 , and CFH.12. The compound of claim 11 , wherein each of R claim 11 , R claim 11 , and Ris H.13. The compound of claim 11 , wherein Ris cyclopropyl.14. The compound of claim 11 , wherein Ris Br and Ris Cl.1511. The compound of any one of claim 11 , claim 11 , and claim 11 , wherein Q is SONH.16. The compound of any of claim 11 , claim 11 , or wherein Q is COH.17. The compound of claim 16 , wherein the salt is Na claim 16 , K claim 16 , Ca claim 16 , Mg claim 16 , or DABCO salt.1817. A pharmaceutical composition comprising a compound of any of - in combination with one or more pharmaceutically acceptable carriers.20. The compound of ...

Herbicidal Phenyltriazolinones

The present invention relates to phenyltriazolinones of formula (I) 114-. (canceled)16. The compound of claim 15 , wherein Ris C-C-alkyl or C-C-haloalkyl claim 15 , Ris C-C-alkyl or C-C-haloalkyl claim 15 , and Y is O.17. The compound of claim 15 , wherein Ris H claim 15 , F or Cl claim 15 , and Ris F claim 15 , Cl or CN.18. The compound of claim 15 , wherein Ris H claim 15 , C-C-alkyl or C-C-alkoxy claim 15 , and Ris H.19. The compound of claim 15 , wherein Ris OR claim 15 , NRS(O)Ror NRS(O)NRR claim 15 , wherein{'sup': '8', 'sub': 1', '6', '3', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '6', '1', '6, 'Ris hydrogen, C-C-alkyl, C-C-alkenyl, C-C-alkynyl, C-C-haloalkyl, C-C-alkoxy-C-C-alkyl, di(C-C-alkoxy)C-C-alkyl, C-C-alkylcarbonyl-C-C-alkyl, C-C-alkoxycarbonyl-C-C-alkyl or C-C-cycloalkyl-C-C-alkyl; and'}{'sup': 9', '10, 'sub': 1', '6, 'R, Rare C-C-alkyl.'}20. The compound of claim 15 , wherein n is 1.21. The compound of claim 15 , wherein Q claim 15 , W and X and Y are O.22. The compound of claim 15 , wherein Z is phenyl or pyridyl claim 15 , each of which is attached to X and Q via vicinal carbon atoms claim 15 , and each of which is optionally substituted by 1 to 4 substituents selected from the group consisting of halogen claim 15 , CN claim 15 , C-C-alkyl claim 15 , C-C-haloalkyl claim 15 , C-C-alkoxy and C-C-haloalkoxy.24. A herbicidal composition comprising an herbicidally active amount of at least one compound of and at least one inert liquid and/or solid carrier and claim 15 , if appropriate claim 15 , at least one surface-active substance.25. A process for the preparation of herbicidal active compositions claim 15 , which comprises mixing an herbicidally active amount of at least one compound of and at least one inert liquid and/or solid carrier and claim 15 , if desired claim 15 , at least one surface-active substance.26. A method of controlling undesired vegetation claim 15 , which ...

2,4,5-TRISUBSTITUTED 1,2,4-TRIAZOLONES USEFUL AS INHIBITORS OF DHODH

The present invention provides triazolone compounds of general formula (I):

Macrolide compounds and their use in liver stage malaria and related disease

A novel quantum-based computational process for drug discovery and design was used to identify potential novel liver-stage anti-malarial therapeutic molecules. The approach combined the latest big-data advances in high-throughput bioassay development with fundamental scientific knowledge to generate new pharmaceutical leads. Several molecules with no previous association with anti-parasitical activity were identified. These molecules and there use in prevention and/or treatment of Plasmodium infections are provided.

NOVEL AZOLE DERIVATIVES AS APELIN RECEPTOR AGONIST

The present invention relates to a novel azole derivative as an apelin receptor agonist and a method for treating cardiovascular disease, diabetic disease, renal disease, hypertension, and arteriosclerosis, etc., using the same. The present invention provides a compound represented by formula (I) or a pharmacologically acceptable salt thereof wherein Xrepresents —N═ or —CH═, Xrepresents —CH═ or —N═, Rand Reach represent a Cto Calkoxy group or the like, Rrepresents a heteroaryl group (the heteroaryl group is optionally substituted by a methyl group or the like) or the like, and Rrepresents a Cto Calkylthio group or a Cto Calkenyl group (the Cto Calkylthio group and the Cto Calkenyl group are each optionally substituted by one carboxy group or the like) or the like. 139-. (canceled)41. The pharmaceutical composition according to claim 40 , wherein Xis —N═; and Xis —CH═.42. The pharmaceutical composition according to claim 40 , wherein Rand Rare each independently a Cto Calkoxy group or a Cto Calkyl group.43. The pharmaceutical composition according to claim 40 , wherein Ris a furyl group claim 40 , a thienyl group claim 40 , a pyridyl group claim 40 , a phenyl group claim 40 , a n-butyl group claim 40 , or a cyclopentyl group claim 40 , wherein the furyl group claim 40 , the thienyl group claim 40 , the pyridyl group claim 40 , and the phenyl group are each optionally substituted by 1 or 2 groups each independently selected from a methyl group and a halogeno group.44. The pharmaceutical composition according to claim 40 , wherein Ris a 5-methylfuran-2-yl group.46. The pharmaceutical composition according to claim 40 , wherein Ris a Cto Calkylthio group claim 40 , an aryl-Cto Calkylthio group claim 40 , a heteroaryl-Cto Calkylthio group claim 40 , a Cto Ccycloalkyl-Cto Calkylthio group claim 40 , a heterocycloalkyl-Cto Calkylthio group claim 40 , a Cto Calkenyl group claim 40 , an aryl-Cto Calkenyl group claim 40 , a heteroaryl-Cto Calkenyl group claim 40 , a Cto ...

LEAD, WIRING MEMBER, PACKAGE PART, METAL PART PROVIDED WITH RESIN AND RESIN-SEALED SEMICONDUCTOR DEVICE, AND METHODS FOR PRODUCING SAME

A semiconductor device and manufacturing method therefor, provided with the aims of constraining resin burr formation while having good electric connectivity and joining strength, and LED device, provided with the aim of improving adhesion between silicon resin and leads while having good luminescent characteristics. For these purposes, an organic film is formed through self-assembly by functional organic molecules at surface border regions of outer leads of a QFP. The functional organic molecules consist of a first functional group bonding with metals, a principal chain, and a second functional group inducing hardening in thermosetting resins. The principal chain consists of a glycol chain, or else of a glycol chain and one or more among methylene, fluoromethylene, or siloxane chains. The principal chain also preferably includes one or more among a hydroxyl radical, ketone, thioketone, primary amine, secondary amine, and aromatic compounds. 138-. (canceled)39. An organic compound forming a self-assembling film by aligning an extremity of a principal chain on a metal surface , whereinthe principal chain comprises:a N-containing heterocycle containing two or more N atoms.40. The organic compound of claim 39 , whereinthe N-containing heterocycle comprises one or more compounds selected from the group consisting of imidazole, triazole, tetrazole, oxydiazole, thiadiazole, pyrimidine, pyridazine, pyridine, and triazine.41. The organic compound of claim 40 , whereinthe principal chain further comprises, farther from the extremity thereof than the N-containing heterocycle, one or more skeletons selected from the group consisting of an aryl skeleton, an acene skeleton, a pyrene skeleton, a phenanthrene skeleton, and a fluorene skeleton.42. An organic compound forming a self-assembling film by aligning an extremity of a principal chain on a metal surface claim 40 , whereinthe principal chain comprises one or more skeletons selected from the group consisting of an aryl ...

TRIAZOLES AS KV3 INHIBITORS

Compounds of formula (I) are of use in the modulation of Kv3.1, Kv.3.2 and Kv3.3 channels and have utility in the treatment or prevention of related disorders. 147.-. (canceled)50. The compound according to claim 48 , wherein ring A has one heteroatom.53. The compound according to claim 48 , wherein Ris H or methyl.54. The compound according to claim 48 , wherein Ris H claim 48 , methyl claim 48 , ethyl claim 48 , isopropyl claim 48 , tert-butyl claim 48 , cyclopropyl claim 48 , Cspiro carbocyclyl claim 48 , trifluoromethyl or 2 claim 48 ,2 claim 48 ,2-trifluorethyl.55. The compound according to claim 48 , wherein Ris H claim 48 , methyl claim 48 , ethyl claim 48 , tert-butyl claim 48 , cyclopropyl claim 48 , trifluoromethyl or 2 claim 48 ,2 claim 48 ,2-trifluorethyl.56. The compound according to claim 48 , wherein Ris absent.57. The compound according to claim 48 , wherein Ris H or absent.58. The compound according to claim 48 , wherein Ris H or is absent.60. The compound according to claim 48 , wherein X is CH.61. The compound according to claim 48 , wherein X is N.62. The compound according to claim 48 , wherein Y is N.63. The compound according to claim 48 , wherein Y is CRand Ris H.64. The compound according to claim 48 , wherein Ris H claim 48 , methyl or ethyl.65. A compound according to which is a compound of any one of Examples 1 to 54.66. A method for the prophylaxis or treatment of hearing disorders claim 48 , schizophrenia claim 48 , bipolar disorder claim 48 , sleep disorders or spinocerebellar ataxia by administering to a subject a compound according to .68. A derivative of a compound of formula (I) according to functionalised via the secondary nitrogen of the triazolone with a group L claim 48 , wherein L is selected from:{'sup': −', '+', '+, 'a) —PO(OH)O.M, wherein M is a pharmaceutically acceptable monovalent counterion,'}{'sup': −', '+, 'sub': '2', 'b) —PO(O).2M,'}{'sup': −', '2+', '2+, 'sub': '2', 'c) —PO(O).D, wherein D is a pharmaceutically ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula X: 29-. (canceled)1215-. (canceled)1824-. (canceled) This application claims the benefit of U.S. Provisional Application No. 61/657,220, filed on Jun. 8, 2012 and U.S. Provisional Application No. 61/774,148, filed on Mar. 7, 2013; the entire disclosures of which are incorporated herein by reference.1. Field of the InventionThe present invention relates to novel compounds which are metabolized in vivo to compounds having activity as neprilysin inhibitors. The invention also relates to pharmaceutical compositions comprising these compounds, processes and intermediates for preparing these compounds and methods of using these compounds to treat diseases such as hypertension, heart failure, pulmonary hypertension, and renal disease.2. State of the ArtCommonly-assigned U.S. Patent Publication No. 2012/0157386, filed on Dec. 14, 2011 to Smith et al., describes novel compounds that have activity as neprilysin inhibitors, the disclosure of which is incorporated herein by reference. In particular, compounds of the genus:are described. Depending upon the variables, compounds within this genus can be referred to as being in the active form or as being a prodrug, which is metabolized in vivo to generate the active form of the compound.In spite of these compounds however, there remains a need for compounds and prodrugs within this genus that have different metabolic and cleavage properties. For example, there remains a need for active compounds and/or prodrug compounds having improved oral absorption and for prodrug compounds that undergo rapid cleavage to form the active compound. This invention is directed to that need.One aspect of the invention relates to a compound of the formula X:where:(i) Ris F; Ris Cl; X isandwhen X is:Ris H and Ris selected from —CHCH, —CHCH(CH), —CHCF, —(CH)CF, —CHCFCH, —CHCFCF, —C(CH)(CF), —CH(CHCH)CF, —CH(CH)CFCF, —(CH)OH, —CHCH(NH)COOCH, —(CH)OCH, —CHROC(O)—Calkyl, —CHROC(O)O— ...

Process for the Preparation of 4-amino-N-tert-butyl-4,5-dihydro-3-isopropyl-5-oxo-1H-1,2,4-triazole-1-carboxamide (Amicarbazone)

The present invention relates to an improved process for the preparation of 4-amino-N-tert-butyl-4,5-dihydro-3-isopropyl-5-oxo-1H-1,2,4-triazole-1-carboxamide (Amicarbazone). The present invention more particularly relates to an improved process for the preparation of 4-amino-N-tert-butyl-4,5-dihydro-3-isopropyl-5-oxo-1H-1,2,4-triazole-1-carboxamide (Amicarbazone) by coupling of 4-Amino-2,4-dihydro-5-(1-methylethyl)-3H-1,2,4-triazol-3-one (TAZ) and poor quality tert-Butyl isocyanate (TBIC) with purity less than or equal to 98%, preferably less than or equal to 85%. 1. A process for the preparation of Amicarbazone comprising reacting 4-Amino-2 ,4-dihydro-5-(1-methylethyl)-3H-1 ,2 ,4-triazol-3-one with tert-Butyl isocyanate having low purity.2. The process as claimed in wherein said tert-Butyl isocyanate is having purity less than or equal to 80% and at least 18% molar excess of TBIC with respect to TAZ is used.3. A process for the preparation of Amicarbazone comprising the step of:i. Preparing a solution of 4-Amino-2,4-dihydro-5-(1-methylethyl)-3H-1,2,4-triazol-3-one (TAZ), Potassium hydroxide and toluene;ii. Raising the temperature of the solution obtained in step (i) to the range of 50° C. to 70° C.;iii. Adding tert-Butyl isocyanate (TBIC) without distillation to the solution of step (ii)iv. Heating the solution obtained at temperature in the range of 60° C. to 75° C.;v. Cooling the solution obtained in step (iv) to form Amicarbazone.4. The process as claimed in claim 1 , wherein the said step iii) comprises at least 18% molar excess of TBIC with respect to TAZ.5. The process as claimed in claim 1 , wherein the solution is cooled to the temperature in the range of 40° C. to 50° C.6. The process as claimed in claim 1 , wherein the cooled solution is optionally seeded with Amicarbazone.7. The process as claimed in claim 1 , wherein tert-Butyl isocyanate (TBIC) have purity equal to or less than 98%.8. The process as claimed in or claim 1 , wherein tert-Butyl ...

HCK INHIBITORS FOR THE TREATMENT OF FIBROSIS AND CANCER

Compounds which are thiazole and triazole derivatives are disclosed, including compounds of the following genus: 2. A compound according to claim 1 , wherein X is O.3. A compound according to claim 1 , wherein X is NR.413-. (canceled)14. A compound according to claim 1 , wherein Ris —C(═O)OR.1516-. (canceled)17. A compound according to claim 1 , wherein:X is O or NH;{'sup': '1', 'Ris selected from optionally substituted phenyl or O;'}{'sup': '2', 'Ris selected from halogen or chloro;'}{'sup': '3', 'Ris selected from O or CN;'}{'sup': 4', '5, 'Ris —C(═O)OR;'}{'sup': '5', 'Ris ethyl; and'}{'img': {'@id': 'CUSTOM-CHARACTER-00042', '@he': '2.79mm', '@wi': '12.36mm', '@file': 'US20220177464A1-20220609-P00001.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, 'independently in each instance indicates a single bond or a double bond.'}20. The compound according to claim 19 , wherein Rand Rform a 5- to 7-membered heterocyclic or heteroaryl ring claim 19 , substituted with R.22. (canceled)24. (canceled)2631-. (canceled)3435-. (canceled)36. The compound according to claim 33 , wherein Ris a 5- or 6-membered heteroaryl.3745-. (canceled)47. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable carrier claim 1 , adjuvant claim 1 , or vehicle.48. A method for treating a disease or disorder in a patient claim 1 , comprising administering to said patient an effective amount of a compound according to claim 1 , wherein said disease or disorder is selected from fibrosis or a fibrotic disease; a chronic kidney disease claim 1 , renal fibrosis claim 1 , or chronic renal allograft injury; solid malignancy or hematological malignancy; an autoimmune or inflammatory disease; or wherein the disease or disorder involves the dysregulation of hematopoietic cell kinase (HCK) signaling.4955-. (canceled)56. A method for inhibiting hematopoietic cell kinase (HCK) activation claim 1 , said method comprising bringing ...

Polymorphic Forms of 2-(5-Bromo-4-(4-Cyclopropylnaphthalen-1-yl)-4H-1,2,4-Triazol-3-ylthio)Acetic Acid and Uses Thereof

Crystalline polymorph forms of 2-(5-bromo-4-(4-cyclopropyl naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid are described. Pharmaceutical compositions and the uses of such compounds, compound forms, and compositions for the treatment of a variety of diseases and conditions are also presented. 2. The method of claim 1 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08 °2θ±0.1 °2θ.3. The method of claim 1 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in .4. The method of claim 1 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate.5. The method of claim 1 , further comprising administering allopurinol.6. The method of claim 1 , further comprising administering febuxostat.8. The method of claim 7 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08 °2θ±0.1 °2θ.9. The method of claim 7 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in .10. The method of claim 7 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 7 ,2 claim 7 ,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate.11. The method of claim 7 , further comprising administering allopurinol.12. The method of claim 7 , further comprising administering febuxostat.14. The method of claim 13 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08 °2θ±0.1 °2θ.15. The method of claim 13 , wherein the crystalline polymorph exhibits an x-ray powder ...

Neprilysin inhibitors

In one aspect, the invention relates to compounds having the formula I: where R 1 -R 6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.

UNSATURATED HETEROCYCLOALKYL AND HETEROAROMATIC ACYL HYDRAZONE LINKERS, METHODS AND USES THEREOF

The present application is directed to compounds of Formula (I), (II), (III) or (IV) compositions comprising these compounds, methods for their preparation and their uses, for example, as acyl hydrazone linkers, which can link two chemical entities together for further use as medicaments and/or diagnostics. 2. The compound of claim 1 , wherein Land Lindependently comprise at least one ester claim 1 , carbonate claim 1 , carbamate or amide linkage and optionally one or more ether claim 1 , sulfone claim 1 , sulfoxide claim 1 , thioether claim 1 , thioamide claim 1 , thioester and amine claim 1 , and optionally one or more C-Calkylene groups claim 1 , C-Calkenylene groups and C-Calkynylene groups.3. The compound of claim 1 , wherein Land Lare independently selected from a direct bond claim 1 , Z claim 1 , R claim 1 , Z—R claim 1 , R—Z claim 1 , R—Z—Rand Z—R—Z claim 1 , wherein Z and Zare independently selected from O claim 1 , S claim 1 , S(O) claim 1 , SO claim 1 , NH claim 1 , N(Calkyl) claim 1 , C(Q) claim 1 , C(Q)Y claim 1 , YC(Q) claim 1 , YC(Q)Y claim 1 , (CalkyleneY)and Y—(CalkyleneY) claim 1 , wherein Rand Rare independently selected from Calkylene claim 1 , Calkenylene and Calkynylene; Q claim 1 , Y and Yare independently selected from O claim 1 , S claim 1 , NH and N(Calkyl); and p is selected from 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 and 6.4. The compound of claim 3 , wherein Rand Rare independently selected from Calkylene claim 3 , Calkenylene and Calkynylene.5. The compound of or claim 3 , wherein Q claim 3 , Y and Yare independently selected from O claim 3 , S claim 3 , NH and N(CH).6. The compound of any one of to claim 3 , wherein Z and Zare independently selected from O claim 3 , S claim 3 , S(O) claim 3 , SO claim 3 , NH claim 3 , N(CH) claim 3 , C(O) claim 3 , C(O)NH claim 3 , NHC(O) claim 3 , NHC(O)O claim 3 , OC(O)O claim 3 , NHC(O)NH claim 3 , OC(O)NH claim 3 , NHC(NH)NH claim 3 , (CalkyleneO)and O—(CalkyleneO).7. The compound of ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula XII: 128-. (canceled)30. The compound or salt of claim 29 , wherein the compound is a compound of Formula (1).31. The compound or salt of claim 29 , wherein the compound is a compound of Formula (2).32. The compound or salt of claim 29 , wherein the compound is a compound of Formula (3).33. The compound or salt of claim 29 , wherein the compound is a compound of Formula (4).36. The method of claim 35 , further comprising contacting the compound of Formula (2) with sodium hydride prior to the contacting of (ii).37. The method of claim 35 , further comprising purifying the compound of Formula (3).39. The method of claim 38 , further comprising contacting the compound of Formula (3) with sodium hexamethyldisilazide prior to the contacting of (iii).40. The method of claim 38 , further comprising purifying the compound of Formula (4).43. The method of claim 42 , further comprising contacting the compound of Formula (3) with sodium hexamethyldisilazide prior to the contacting of (iii).44. The method of claim 42 , further comprising purifying the compound of Formula (4).47. The method of claim 46 , further comprising contacting the compound of Formula (2) with sodium hydride prior to the contacting of (ii).48. The method of claim 46 , further comprising purifying the compound of Formula (3). This application claims the benefit of U.S. Provisional Application No. 61/657,229, filed on Jun. 8, 2012 and U.S. Provisional Application No. 61/773,969, filed on Mar. 7, 2013; the entire disclosures of which are incorporated herein by reference.The present invention relates to novel compounds which are metabolized in vivo to compounds having activity as neprilysin inhibitors. The invention also relates to pharmaceutical compositions comprising these compounds, processes and intermediates for preparing these compounds and methods of using these compounds to treat diseases such as hypertension, heart failure, ...

ARYL SULFIDE DERIVATIVES AND ARYL SULFOXIDE DERIVATIVES AS ACARICIDES AND INSECTICIDES

The present invention relates to aryl sulfoxide derivatives, to the use thereof as acaricides and insecticides for controlling animal pests and to processes and intermediates for preparation thereof. The aryl sulfide and aryl sulfoxide derivatives have the general structure (I) 3. The compound as claimed in in whichA and B together with the atoms to which they are attached represent a substructure selected from the group consisting of (I-A) to (I-D),where{'sup': 1', '2', '3, 'claim-text': {'sup': 11', '11, 'represent oxygen; sulfur, NRor a salt of NR;'}, 'V, Vand Veach independently of one another'}{'sup': 1', '1', '2, 'Qrepresents oxygen, sulfur, NRor CRR;'}{'sup': 2', '10', '8', '9, 'Qrepresents NRor CRR;'}{'sup': '1', 'claim-text': represents alkyl, cycloalkylalkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkoxycarbonylalkyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkylsulfanylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkoxyalkylsulfanylalkyl, alkoxyalkylsulfinylalkyl, alkoxyalkylsulfonylalkyl, phenylalkyl, phenoxyalkyl, phenylsulfanylalkyl, phenylsulfinylalkyl, phenylsulfonylalkyl, hetarylalkyl, hetaryloxyalkyl, hetarylthioalkyl, alkoxycarbonyl, aryloxycarbonyl, arylcarbamoyl, where the aforementioned radicals may each be saturated or unsaturated and/or optionally substituted; or', 'represents optionally substituted saturated or unsaturated cycloalkyl which may optionally be interrupted by one or more heteroatoms; or', 'represents haloalkylcarbonyl, hydroxyalkylcarbonyl, alkoxyalkylcarbonyl, phenylcarbonyl, hetarylcarbonyl, haloalkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkylaminocarbonyl, dicycloalkylaminocarbonyl, cycloalkyl(alkyl)aminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, alkyl(aryl)aminocarbonyl, cycloalkyl(aryl)aminocarbonyl, alkylaminothiocarbonyl, dialkylaminothiocarbonyl or aminothiocarbonyl, where the aforementioned radicals may each be saturated ...

Fungal control of white mold

A fungicidal composition containing a fungicidally effective amount of a compound of Formula I, (3S,6S,7R,8R)-8-benzyl-3-(3-((isobutyryloxy)nethoxy)-4-methoxy-picolinamido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate for use on white mold. Additionally, this disclosure concerns a fungicidal composition containing (a) a compound of Formula I, (3S,6S,7R,8R)-8-benzyl-3-(3-((isobutyryloxy)methoxy)-4-methoxypicolinamido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate and (b) at least one fungicide selected from the group consisting of azoxystrobin, prothioconazole and tebuconazole for control of white mold.

PROCESS FOR PREPARATION OF SULFENTRAZONE WITH TANK-MIX COMPATIBILITY

Described herein is an environmentally friendly process for preparing pure sulfentrazone having tank-mix compatibility which includes treating sulfentrazone with a base and isolating the pure sulfentrazone with an acid. Compositions containing the pure sulfentrazone are also included. 1. A process for preparing sulfentrazone comprises treating a solid form of sulfentrazone with an aqueous base and isolating pure sulfentrazone with an acid , wherein said process is carried out without using an organic solvent.2. The process as claimed in claim 1 , wherein said process is carried out in an aqueous medium.3. The process as claimed in claim 1 , wherein said base is selected from organic or inorganic base.4. The process as claimed in claim 1 , wherein said base is selected from the group of alkali or alkaline earth metal hydroxides claim 1 , alkali metal or alkaline earth metal carbonates claim 1 , alkaline earth metal oxides claim 1 , p-block element carbonates claim 1 , transition metal carbonates claim 1 , ammonia or amines.5. The process as claimed in claim 1 , wherein said base is selected from the group comprising of lithium carbonate claim 1 , lithium bicarbonate claim 1 , sodium carbonate claim 1 , sodium bicarbonate claim 1 , potassium carbonate claim 1 , potassium bicarbonate or ammonia.6. The process as claimed in claim 1 , wherein said acid is selected from organic or inorganic acid.7. The process as claimed in claim 1 , wherein said acid is selected from the group comprising of hydrochloric acid claim 1 , sulfuric acid claim 1 , nitric acid claim 1 , phosphoric acid claim 1 , boric acid claim 1 , hydrofluoric acid claim 1 , hydrobromic acid claim 1 , perchloric acid claim 1 , hydroiodic acid claim 1 , acetic acid claim 1 , formic acid or oxalic acid.8. A process for preparing sulfentrazone comprisinga) treating a solid form of sulfentrazone with an aqueous base to obtain a medium comprising sulfentrazone salt;b) isolating pure sulfentrazone by adjusting pH ...

METHOD OF SYNTHESIZING 1,2,4-TRIAZOLE-3-THIONE COMPOUNDS AND INTERMEDIATES THEREOF

Disclosed is a method of synthesizing 1,2,4-triazole-3-thione compounds and intermediates thereof. The method includes reacting a hydrazine with glyoxylic acid to form a hydrazono acetic acid intermediate followed by reacting the latter with thiocyanate to obtain the 1,2,4-triazole-3-thione compound. The raw materials involved in the present method are readily available, and the reaction is very specific in terms of regioselectivity, resulting in minimum by-product and high product yield. There are neither specific requirements for special equipment nor special operations such as high vacuum, high temperature, anhydrous and oxygen-free manipulations. The process is simple and generates minimum wastes, suitable for industrial production. 2. The method of claim 1 , wherein step 1 is carried out in the presence or absence of a solvent; a molar ratio of compound 6 or 6′ to compound 7 or 7′ is 1:1-10;and a reaction temperature in step 1 is 0-40° C.3. The method of claim 2 , wherein the solvent is selected from water claim 2 , acetonitrile claim 2 , tert-butanol claim 2 , dichloromethane claim 2 , DMF claim 2 , DMSO and toluene or mixture thereof.4. The method of claim 1 , wherein steps 1 and 2 are carried out in a stepwise or a one-pot manner.6. The method of claim 1 , wherein in step2 claim 1 , compound 8 or 8′ is reacted with M′SCN in the presence of an acid; a molar ratio of compound 8 or 8′ to M′SCN is 1:1-5; and a reaction temperature is 50-80° C.7. The method of claim 5 , wherein compound 8 or 8′ is reacted with M′SCN in the presence of an acid; a molar ratio of compound 8 or 8′ to M′SCN is 1:1-5; and a reaction temperature is 50-80° C.8. The method of claim 6 , wherein the acid is an organic acid; and a molar ratio of the acid to compound 8 or 8′ is 0.01-100:1.9. The method of claim 7 , wherein the acid is an organic acid; and a molar ratio of the acid to compound 8 or 8′ is 0.01-100:1.10. The method of claim 8 , wherein the organic acid is selected from formic ...

SUBSTITUTED PHENYL SULFONYL PHENYL TRIAZOLE THIONES AND USES THEREOF

The present disclosure relates to substituted phenyl sulfonyl phenyl triazole thiones, pharmaceutical compositions containing them, and methods of using them. 123-. (canceled)25. The pharmaceutical composition of claim 24 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of hydroxypropylmethyl cellulose (HPMC) claim 24 , polyvinylpyrrolidone (PVP) claim 24 , and Kollidon.26. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition is in the form of a spray dry dispersion (SDD).28. The method of claim 27 , wherein the condition associated with neurodegeneration or accumulation of proteins is Alzheimer's Disease claim 27 , Parkinson's Disease claim 27 , fronto-temporal dementia claim 27 , dementia with Lewy Bodies claim 27 , PD dementia claim 27 , multiple system atrophy claim 27 , Huntington's disease claim 27 , Amyotrophic lateral sclerosis claim 27 , progressive supranuclear palsy claim 27 , cancer claim 27 , infection claim 27 , Crohn's disease claim 27 , heart disease claim 27 , aging claim 27 , or traumatic brain injury (TBI).30. The method of claim 29 , wherein the protease-resistant protein is selected from alpha synuclein claim 29 , a-beta claim 29 , tau claim 29 , Huntingtin claim 29 , and TAR DNA binding protein 43 (TDP43) proteins.31. The method of claim 27 , wherein Ris hydrogen.32. The method of claim 27 , wherein Ris —OCHCH—O—CHCHor —OCHCHOCH.33. The method of claim 27 , wherein Ris —NHCHCHOH or —N(CHCH).34. The method of claim 27 , wherein Ris morpholinyl claim 27 , 4-methyl-piperazin-1-yl claim 27 , piperidinyl claim 27 , or pyrrolidinyl.35. The method of claim 27 , wherein Ris hydrogen claim 27 , Calkyl claim 27 , or substituted Calkyl.36. The method of claim 27 , wherein Ris CF.37. The method of claim 27 , wherein Ris methyl.38. The method of claim 27 , wherein Ris optionally substituted Calkoxy claim 27 , —CN claim 27 , or —NRR.39. The method of claim 27 , wherein Ris —N(CH).40. The ...

2,4,5-TRISUBSTITUTED 1,2,4-TRIAZOLONES USEFUL AS INHIBITORS OF DHODH

The present invention provides triazolone compounds of general formula (I): in which R, R, R, Rand Rare as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients. 2. The compound of formula (I)in which{'sup': '1', 'claim-text': [{'sub': 5', '8, 'a C-C-alkyl group,'}, {'sub': 2', '8, 'a C-C-haloalkyl group,'}, {'sub': 4', '8, 'claim-text': {'sup': 7', '8, 'claim-text': wherein said phenyl substituent is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from', {'sub': 1', '3', '1', '4', '1', '3, 'C-C-alkyl, C-C-haloalkyl, C-C-alkoxy and hydroxy,'}], 'wherein said cycloalkyl groups are optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from hydroxy, phenyl and —N(R)(R),'}, 'a C-C-cycloalkyl group,'}, {'sub': 1', '6', '3', '8, 'a C-C-alkyl group which is substituted with a C-C-cycloalkyl group,'}, {'sub': 2', '6, 'a C-C-alkyl group which is substituted with a cyano group, a hydroxy group or a phenyl group,'}, {'sub': 3', '6, 'a C-C-alkyl group which is substituted with a monocyclic- or bicyclic heteroaryl group,'}, {'sub': 2', '6', '2', '6, 'a (C-C-hydroxyalkyl)-O—(C-C-alky)- group,'}, {'sub': 3', '6, 'sup': 7', '8, 'a —(C-C-alkyl)-N(R)(R) group,'}, {'sub': 3', '8, 'sup': 7', '8, 'a —(C-C-cycloalkyl)-N(R)(R) group,'}, {'sub': 3', '6, 'sup': 7', '8, 'a —(C-C-alkyl)-C(═O)N(R)(R) group,'}, which is optionally substituted one or two times, each substituent independently selected from a group selected from', {'sub': 1', '3', '1', '4', '1', '6', '3', '6', '2', '1', '6, ' ...

Manufacturing process and intermediates for a pyrrolo[2,3-d]pyrimidine compound and use thereof

The present invention relates to a manufacturing process and intermediates for preparing a crystalline or non-crystalline form of N-((1S,3S)-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclobutyl)propane-1-sulfonamide. The present invention also relates to salt forms and pharmaceutical compositions comprising the crystalline form, and to methods for use of the compound prepared from a crystalline form in the treatment of various diseases.

GPR17 Receptor Modulators

Chemical compounds are provided which act on GPR17 receptors and are useful in the treatment or amelioration of chronic and/or acute neurodegenerative diseases, such as multiple sclerosis, inflammatory diseases, pathologies involving the immune system, cardiovascular diseases, and renal diseases. 117-. (canceled)19. The compound of claim 18 , wherein Rand Rare independently H or an optionally substituted phenyl claim 18 , or Rand Rare closed to form with the N to which are linked a 1 claim 18 ,2 claim 18 ,3 claim 18 ,4-tetrahydroquinoline claim 18 , a 1 claim 18 ,2 claim 18 ,3 claim 18 ,4-tetrahydroisoquinoline claim 18 , a pirrolidine claim 18 , a piperidine claim 18 , a piperazine optionally substituted;A is C and the formed 6 membered ring is preferably an aromatic ring;Z forms a bicycle with said 6 membered ring by closing on A, wherein said second ring formed by Z is a 5 membered ring open to fusion, preferably said 5 membered ring is fused with an optionally substituted phenyl forming a tricycle, preferably said tricycle is a 5H-[1,2,4]triazino[5,6-b]indole optionally substituted; andR is H or C1-C4 aryl.21. The compound of wherein Formula (III) is selected from the group consisting of: 3-[[2-(2 claim 18 ,3-dihydro-1H-indol-1-yl)-2-oxoethyl]thio]-N-(2-methylphenyl)-9H-1 claim 18 ,2 claim 18 ,4-Triazolo[4 claim 18 ,3-a]benzimidazole-9-acetamide claim 18 , 2-[9-(4-Chloro-benzyl)-9H-benzo[4 claim 18 ,5]imidazo[2 claim 18 ,1-c][1 claim 18 ,2 claim 18 ,4]triazol-3-ylsulfanyl]-1-(3 claim 18 ,4-dihydro-1H-isoquinolin-2-ethanone claim 18 , 2-(9-Benzyl-9H-benzo[4 claim 18 ,5]imidazo[2 claim 18 ,1-c][1 claim 18 ,2 claim 18 ,4]triazol-3-ylsulfanyl)-1-pyrrolidin-1-yl-ethanone claim 18 , 2-[9-(4-Chloro-benzyl)-9H-benzo[4 claim 18 ,5]imidazo[2 claim 18 ,1-c][1 claim 18 ,2 claim 18 ,4]triazol-3-ylsulfanyl]-1-pyrrolidin-1-yl-ethanone claim 18 , 2-[3-(2-Oxo-2-piperidin-1-yl-ethylsulfanyl)-benzo[4 claim 18 ,5]imidazo[2 claim 18 ,1-c][1 claim 18 ,2 claim 18 ,4]triazol-9-yl]-1- ...

THIOETHER COMPOUNDS AS NITRIFICATION INHIBITORS

Provided herein are a use of thioether compounds of formula I as nitrification inhibitors, and agricultural mixtures and compositions including the thioether compounds. 2. The thioether compound of claim 1 , wherein in the compound of formula I{'sup': 1', '2, 'Rand Rare H; and'}p is 1 or 2.6. A composition for use in reducing nitrification comprising at least one compound of formula I as defined in and at least one carrier.7. An agrochemical mixture comprising (i) at least one fertilizer; and (ii) at least one compound of formula I as defined in .8. (canceled)9. (canceled)10. A method for reducing nitrification claim 1 , the method comprising treating a plant growing on at least one of soil claim 1 , soil substituents claim 1 , and a locus claim 1 , soil claim 1 , and soil substituents where the plant is growing or is intended to grow with at least one compound of formula I as defined in .11. The method of claim 10 , further comprising providing the at least one of the plant and the locus claim 10 , soil claim 10 , and soil substituents where the plant is growing or is intended to grow with a fertilizer.12. The method of claim 11 , wherein the treating with the compound of formula I and the providing of the fertilizer are carried out simultaneously.13. A method for treating at least one of a fertilizer and a fertilizer composition claim 1 , comprising applying a nitrification inhibitor as defined in to the at least one of the fertilizer and the fertilizer composition.14. The agrochemical mixture of claim 7 , wherein the fertilizer is selected from the group consisting of a solid ammonium-containing inorganic fertilizer claim 7 , a liquid ammonium-containing inorganic fertilizer claim 7 , a solid organic fertilizer claim 7 , a liquid organic fertilizer claim 7 , and a urea-containing fertilizer.15. The method of claim 10 , wherein the plant is an agricultural plant claim 10 , a vegetable claim 10 , sorghum; a silvicultural plant; an ornamental plant; and a ...