ПИРАЗОЛЬНЫЕ СОЕДИНЕНИЯ, ОБЛАДАЮЩИЕ ТЕРАПЕВТИЧЕСКИМ ЭФФЕКТОМ НА МНОЖЕСТВЕННУЮ МИЕЛОМУ

Изобретение относится к пиразольному соединению, имеющему приведенную ниже формулу (1), где Rпредставляет собой C-Cалкил, C-Cалкил, замещенный группой R, C-Cгалогеналкил, фенил, фенил, замещенный a количеством заместителей R, или т.п., Rпредставляет собой атом водорода, C-Cалкил, фенил или фенил, необязательно замещенный e количеством заместителей R, или т.п., Rпредставляет собой атом водорода или т.п., X представляет собой простую связь или -(CRR)-, каждый из Rи Rнезависимо представляет собой C-Cалкил или т.п., Rи Rпредставляют собой атомы водорода или C-Cалкил, Rпредставляет собой фенил, фенил, необязательно замещенный k количеством заместителей R, или т.п., таутомеру такого соединения или его фармацевтически приемлемой соли. Данное соединение ингибирует рост клеток множественной миеломы. Изобретение также относится к терапевтическому средству для лечения множественной миеломы, содержащей пиразольное соединение, представленное формулой (1), в качестве активного ингредиента.2 н. и 7 з.п ...

ПРИМЕНЕНИЕ N-ФУНКЦИОНАЛИЗИРОВАННЫХ АЛКОКСИПИРАЗОЛЬНЫХ СОЕДИНЕНИЙ В КАЧЕСТВЕ ИНГИБИТОРОВ НИТРИФИКАЦИИ

Изобретение относится к новым ингибиторам нитрификации. Предложено применение N-функционализированного алкоксипиразольного соединения формулы I, или его соли, в качестве ингибитора нитрификации, где R1 означает C1-C2-алкил, или бензил; R2 означает C1-C2-алкил; RN означает CH(C(=O)ORb)CH2(C(=O)ORb); C(=O)Rd или C(=O)NRbRc, где Rb означает Н; Rc означает Н; Rd означает С1-С3-алкил; n означает 0 или 1. Также предложены применение композиции, содержащей соединение формулы I, агрохимическая смесь, способ снижения нитрификации и способ обработки удобрения. Технический результат – получение ингибитора нитрификации, который имеет высокую активность в качестве ингибиторов нитрификации, обладает пониженной летучестью и токсичностью, а также является экологически безопасным. 5 н. и 8 з.п. ф-лы, 1 пр., 11 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.

ПРОИЗВОДНЫЕ ПИРАЗОЛА ДЛЯ ЛЕЧЕНИЯ ВИРУСНЫХ ЗАБОЛЕВАНИЙ

Изобретение относится к производным пиразола формулы I-A где R1 означает (С1-С12)алкил, который необязательно может быть замещен 1-3 заместителями, выбранными из фтора, хлора и брома, (С3-С8)циклоалкил, фенил, пиридил или (С1-С4)алкил, замещенный фенилом; R2' означает необязательно замещенный фенил, где фенил может быть замещен 1-2 заместителями, выбранными из (С1-С4)алкила, (С1-С4)алкоксила, гидроксила, фтора, хлора, брома, циангруппы и нитрогруппы; R3 означает (С1-С12)алкил или (С1-С4)алкокси-(С1-С4)алкил; А' означает (С1-С4)алкил, замещенный необязательно замещенным фенилом или необязательно замещенным 4-пиридилом, где фенил или 4-пиридил могут быть замещены 1-2 заместителями, выбранными из (С1-С4)алкила, (С1-С4)алкоксила, гидроксила, фтора, хлора, брома, циангруппы и NRR', где R и R' независимо друг от друга означают водород или (С1-С4)алкил, или А' означает группу формулы СН2-U-гетероциклил, где U представляет O, S или NR'', где R'' означает водород или (С1 -С4)алкил и где гетероциклил ...

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 ...

ЗАМЕЩЕННЫЕ АРИЛКЕТОНЫ И ГЕРБИЦИДНОЕ СРЕДСТВО НА ИХ ОСНОВЕ

Изобретение относится к новым замещенным арилкетонам формулы (I) в которой A1, A2, Q, R1, R2, X, Y и Z имеют значения, указанные в описании. Соединения, указанные в настоящей заявке, являются биологически активными и могут быть использованы в качестве дефолиантов, десикантов, средств для предуборочного уничтожения ботвы или в качестве средства для уничтожения сорняков. В настоящем изобретении также представлены промежуточные соединения для получения соединения общей формулы (I) такие как или Цель данного изобретения - получение гербицидного средства на основе соединения общей формулы (I) и обычных наполнителей, проявляющего высокую активность против сорняков. 4 н. и 8 з.п. ф-лы, 4 табл.

КИСЛОРОДЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ 3-ГЕТЕРОАРОИЛАМИНОПРОПИОНОВЫХ КИСЛОТ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ФАРМАЦЕВТИЧЕСКИХ СРЕДСТВ

Изобретение относится к соединениям формулы I и их фармацевтически приемлемым солям, где А представляет собой C(R); D представляет собой N(R); Е представляет собой N; G выбирают из группы, состоящей из R-O-C(O)- и R-N(R)-С(O)-; Rвыбирают из водорода, галогена и (С-С)-алкила; Rвыбирают из (C-C)-алкила, (С-С)-циклоалкил-CH- и Ar-CH-, где s равен 0, 1, 2 и 3; Rвыбирают из R-O-, R-N(R)-С(О)-О- и Het-C(O)-О-; Rвыбирают из водорода, R, (С-С)-циклоалкила и Ar; Rи Rнезависимо друг от друга выбирают из водорода, Rи Ar; Rпредставляет собой (C-С)-алкил, который необязательно замещен 1-3 одинаковыми или различными заместителями, выбранными из галогена, НО-, R-O-, оксо, (С-С)-циклоалкила, необязательно замещенного 1-3 атомами фтора, Ar, Het, Het, ди((C-C)-алкил)N-С(О)- и Het-C(O)-; Rпредставляет собой (С-С)-алкил; Rпредставляет собой (C-C)-алкил, который необязательно замещен (С-С)-алкил-О-; Rвыбирают из группы, состоящей из R, R-CH- и Het-CH-, где u равен 0; R, Rи Rявляются такими, как указано в формуле ...

ИНГИБИТОРЫ ФЕРМЕНТА ДИАЦИЛГЛИЦЕРИН О-АЦИЛТРАНСФЕРАЗА ТИПА 1

Изобретение относится к соединениям формулы (I) или их фармацевтически приемлемым солям, где Q является фенилом или пиридинилом; А является пиразолилом или триазолилом, где каждый А является независимо дополнительно незамещенным или замещенным 1 или 2 заместителями, представленными R, или А является формулой (a); Vявляется C(R), Vявляется N или C(R) и Vявляется N; иди Vявляется N, Vявляется C(R) и Vявляется N или C(R); Rявляется водородом, Rявляется водородом, Салкилом, -OR, -SR, арилом, выбранным из фенила, гетероарилом, выбранным из тиенила, или циклоалкилом, выбранным из циклопропила; Rявляется водородом или арилом, выбранным из фенила; Rявляется водородом или Салкилом; Rявляется водородом, Салкилом, -OH, -S(O)R, или гетероарилом, выбранным из тетразолила, где гетероарил соединен с атомом азота через углеродный атом кольца; R, R, R, R, R, R, R, R, R, R, Rи R, в каждом случае, являются независимо водородом, Салкилом или Сгалогеналкилом; и Rв каждом случае, является независимо водородом ...

4-(АРИЛАМИНОМЕТИЛЕН)-2,4-ДИГИДРОПИРАЗОЛ-3-ОНЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Изобретение относится к 4-(ариламинометилен)-2,4-дигидропиразол-3-онам общей формулы I, где R1 обозначает бензил, алкоксибензил с 1-3 С-атомами в алкильной части, незамещенный или замещенный однократно - трехкратно амино, ацилом, галогеном, нитро, CN, АО-, карбоксилом, карбамоилом, N-алкилкарбамоилом, N, N-диалкилкарбамоилом (с 1-6 С-атомами в алкильной части), A-CO-NH-, А-О-СО-NH-, А-О-СО-NA-, SO2NR4R5 (R4 и R5 могут обозначать Н или алкил с 1-6 С-атомами или NR4R5 представляет 5- или 6-членное кольцо, на выбор с другими гетероатомами, как N, или О, которое может быть замещено А), А-СО-NH-SO2-, A-CO-NA-SO2-, (А-SO2-)2N-, тетразолилом фенил; или пиридил; R2 обозначает алкил с 1-5 С-атомами, этоксикарбонилметил, гидроксикарбонилметил; R3 обозначает неразветвленный или разветвленный алкил с 1-5 С-атомами, неразветвленный или разветвленный алкокси с 1-5 С-атомами или СF3 А обозначает неразветвленный или разветвленный алкил с 1-6 С-атомами или СF3, а также к их солям. Соединения являются избирательными ...

СПОСОБ ПОЛУЧЕНИЯ СОЕДИНЕНИЯ 5-АЛКОКСИ-4-ГИДРОКСИМЕТИЛПИРАЗОЛА

Настоящее изобретение относится к способу получения соединения 5-алкокси-4-гидроксиметилпиразола, представленного общей формулой (3), где R1 представляет собой С1-С6 алкильную группу или фенильную группу, R2 представляет собой С1-С6 галогеналкильную группу, цианогруппу или (С1-С6 алкокси)карбонильную группу и R3 представляет собой С1-С6 алкильную группу, которая может быть незамещенной или замещенной галогеном, фенильной группой или (С1-С6 алкокси)карбонильной группой, С3-С8 циклоалкилалкильную группу, С2-С6 алкенильную группу или С2-С6 алкинильную группу. Предложенный способ включает реакцию соединения пиразола, представленного общей формулой (1), с соединением, представленным общей формулой (2), где L представляет собой уходящую группу, и формальдегидом в присутствии основания, где R1, R2 и R3 имеют значения, указанные выше. Изобретение также относится к новым соединениям 5-алкокси-4-гидроксиметилпиразола. Технический результат - предложенный способ позволяет простым образом и с высокой ...

2-[(ДИГИДРО)ПИРАЗОЛИЛ-3'-ОКСИМЕТИЛЕН]АНИЛИДЫ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ, ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ, СРЕДСТВО БОРЬБЫ С СЕЛЬСКОХОЗЯЙСТВЕННЫМИ ВРЕДИТЕЛЯМИ И ВРЕДОНОСНЫМИ ГРИБАМИ И СПОСОБЫ БОРЬБЫ

Описываются новые соединения - 2-[(дигидро)пиразолил-3'-оксиметилен] анилиды формулы I, в которой означает простую, либо двойную связь, а индексы и заместители имеют следующее значение: n означает 0, 1 или 2; m означает 0, 1 или 2, причем заместители R2 могут быть различными, если m больше 1; Х означает прямую связь, О или NRa; Ra означает водород; R1 означает С1-С4алкил, галоген или в случае, когда n обозначает 2, представляет собой дополнительно связанный с двумя смежными атомами кольца углеводородный мостик, включающий 3 или 4 атома углерода; R2 означает нитро, галоген, С1-С4алкил, С1 -С4галогеналкил или С1-С4алкоксикарбонил; R3 означает необязательно замещенный алкил, необязательно замещенный насыщенный цикл, или необязательно замещенный одно-, либо двухъядерный ароматический радикал, который наряду с атомами углерода может содержать в качестве членов цикла от одного до четырех атомов азота; R4 означает водород, необязательно замещенный алкил; R5 означает алкил, или в случае, если Х ...

ПИРАЗОЛОНОВЫЕ СОЕДИНЕНИЯ ИЛИ ИХ СОЛИ, СПОСОБ ИХ ПОЛУЧЕНИЯ, ГЕРБИЦИДНАЯ КОМПОЗИЦИЯ И ЕЕ ПРИМЕНЕНИЕ

Настоящее изобретение относится к пиразолоновому соединению формулы I или его соли, способу его получения, гербицидной композиции и ее применению. В формуле I RRN представляет собой незамещенный пиразолил или имидазолил; пиразолил, замещенный одной или двумя группами, выбранными из фтора, хлора, Cалкила и Cалкокси; или метокси- или этоксизамещенную или незамещенную 5-8-членную лактамовую группу, содержащую 0-2 гетероатома, выбранных из O, S и N; или Rи Rкаждый представляет собой водород, незамещенный Cалкил или Cалкил, замещенный атомами галогена, Cалкокси или метоксиэтокси; или Cацил, незамещенный или замещенный галогеном или Cалкокси; Rпредставляет собой водород, Cалкил, незамещенный Cциклоалкил или Cциклоалкил, замещенный Cалкилом; Rпредставляет собой метил, этил, н-пропил, изопропил или циклопропил; X представляет собой водород, -S(O)R, -(C=O)R, где Rпредставляет собой этил и n означает 2, Rпредставляет собой Cалкокси, метил, незамещенный N-метилпиразолил или N-метилпиразолил, замещенный ...

ПИРАЗОЛЬНЫЕ СОЕДИНЕНИЯ ИЛИ ИХ СОЛИ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ, ГЕРБЕЦИДНЫЕ КОМПОЗИЦИИ И ИХ ПРИМЕНЕНИЕ

Настоящее изобретение относится к области пестицидов, в частности относится к пиразольному соединению формулы (I) или к его соли, а также к вариантам соединения формулы (I), способу их получения, гербицидной композиции и ее применению. В формуле (I) Rпредставляет собой водород или C1-C4 алкил; Rпредставляет собой C1-C3 алкил; Rпредставляет собой -XR’, где X представляет собой O, S или N, X и R’ может образовывать кольцо или линейную цепь, когда X представляет собой O или S, R’ представляет собой C1-C6 алкил, C3-C6 алкоксиалкил, C2-C6 галогенированный алкил, C3-C6 алкенил, C3-C6 алкинил или тетрагидрофурфурил; когда X представляет собой N, X и R’ образует пиразольное кольцо, 3-метилпиразольное кольцо, 4-метилпиразольное кольцо, 3,5-диметилпиразольное кольцо или 4-хлорпиразольное кольцо; Rпредставляет собой C1-C3 алкил или галоген; Rпредставляет собой пиразольное кольцо или пиразольное кольцо, замещенное одной или несколькими группами, выбранными из C1-C3 алкила, C1-C3 алкоксила, галогена ...

5-ЧЛЕННОЕ ГЕТЕРОЦИКЛИЧЕСКОЕ СОЕДИНЕНИЕ И ЕГО ПРИМЕНЕНИЕ ДЛЯ ЛЕКАРСТВЕННЫХ ЦЕЛЕЙ

... 1. 5-членное гетероциклическое соединение, представленное общей формулой (I) ! ! где Т представляет собой нитро, циано, трифторметил или атом галогена; ! кольцо J представляет собой кольцо арила или кольцо гетероарила; ! Q представляет собой карбокси, низший алкоксикарбонил, карбамоил, моно(ди)(низший алкил)карбамоил, сульфо, сульфамоил или 5-тетразолил; ! Х1 и Х2 независимо представляют собой CR2 или N, при условии, что оба из Х1 и Х2 одновременно не представляют собой N и, когда присутствуют два или более R2, эти R2 необязательно являются одинаковыми или отличными друг от друга; ! R2 представляет собой атом водорода или необязательно замещенный низший алкил; ! Y представляет собой атом водорода, гидрокси, амино, атом галогена, перфтор(низший алкил), необязательно замещенный низший алкил, необязательно замещенный низший алкокси, нитро, (низший алкил)карбониламино или (низший алкил)сульфониламино, при условии, что два или более Y необязательно присутствуют на кольце J, и эти Y необязательно ...

ПРОИЗВОДНЫЕ 6-АМИНО-5,6,7,8-ТЕТРАГИДРОНАФТАЛЕН-2-ИЛА ИЛИ 3-АМИНОХРОМАН-7-ИЛА В КАЧЕСТВЕ МОДУЛЯТОРОВ TAAR

ФУНГИЦИДНЫЕ ПИРАЗОЛЫ

СПОСОБЫ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ ПИРАЗОЛ-О-ГЛИКОЗИДА И НОВЫХ ПРОМЕЖУТОЧНЫХ СОЕДИНЕНИЙ ДЛЯ ПРИМЕНЕНИЯ В УКАЗАННЫХ СПОСОБАХ

... 1. Способ получения соединений общей формулы(I) ! ! где R1 означает C1-C4алкил, C1-C4алкил, замещенный одним или более атомами фтора, или C3-C6циклоалкил; ! R2 означает C1-C4алкил, C1-C4алкил, замещенный одним или более атомами фтора, или C3-C6циклоалкил; ! R3 означает фтор, хлор, бром, C1-C4алкил, C3-C6циклоалкил, C1-C4алкокси или C3-C6циклоалкилокси; ! R4, R5 независимо друг от друга означают водород, фтор, хлор, бром, С1-C4алкил или C1-C4алкокси; ! R6, R7a, R7b, R7c независимо друг от друга выбирают из группы, включающей водород, C1-С6алкилкарбонил, фенилкарбонил и фенил(C1-C3)алкилкарбонил, включая их таутомеры, стереоизомеры, и их смеси и их соли, ! заключающийся в том, что агликон формулы (III) ! ! где R1-R5 имеют значения, указанные выше, ! получают каталитическим гидрированием соединения формулы (IV) ! ! где R1-R5 имеют значения, указанные выше, а ! Q означает Cl, Br, I, C1-C4алкокси, C1-C4алкилтио, фенилтио, С3-C6циклоалкилокси, C1-C4алкилкарбонилокси, -NRaRb, где Ra, Rb независимо ...

ФУНГИЦИДНЫЕ ПИРАЗОЛЫ

... 1. Соединение, выбранное из формулы 1, его N-оксидов и солей,гдеQпредставляет собой фенильное кольцо или нафталинильную кольцевую систему, причем каждое кольцо или кольцевая система необязательно замещены до 5 заместителями, независимо выбранными из R; или 5-6-членное полностью ненасыщенное гетероциклическое кольцо или 8-10-членную гетероароматическую бициклическую кольцевую систему, причем каждое кольцо или кольцевая система, содержащая кольцевые члены, выбранные из атомов углерода, и до 4 гетероатомов, независимо выбранных из до 2 атомов O, до 2 атомов S и до 4 атомов N, где до 3 углеродных кольцевых членов независимо выбрано из C(=O) и C(=S), а кольцевые члены с атомами серы независимо выбраны из S(=O)(=NR), причем каждое кольцо или кольцевая система необязательно замещены до 5 заместителями, независимо выбранными из Rна кольцевых членах с атомами углерода, и выбранных из циано, C-Cалкила, C-Cалкенила, C-Cалкинила, C-Cциклоалкила, C-Cалкокси, C-Cалкоксиалкила, C-Cалкилкарбонила, C-Cалкоксикарбонила ...

АЗОТОСОДЕРЖАЩЕЕ ГЕТЕРОЦИКЛИЧЕСКОЕ ПРОИЗВОДНОЕ, ОБЛАДАЮЩЕЕ ИНГИБИРУЮЩЕЙ АКТИВНОСТЬЮ В ОТНОШЕНИИ 11 БЕТА-ГИДРОКСИСТЕРОИДДЕГИДРОГЕНАЗЫ ТИПА 1

... 1. Соединение, представленное Формулой (I): ! Формула 1 ! , ! его фармацевтически приемлемая соль или их сольват, где кольцо А представляет собой группу, представленную формулой: ! Формула 2 ! или , ! кольцо В представляет собой необязательно замещенный гетероарил, при условии, что исключен необязательно замещенный изоксазолил, или необязательно замещенный гетероцикл, ! R1 представляет собой водород или необязательно замещенный алкил, ! R2 представляет собой -OR5, -SR5, галоген, галогенированный алкил, галогенированную алкоксигруппу, гидроксигруппу, цианогруппу, нитрогруппу, карбоксигруппу, необязательно замещенный алкил, необязательно замещенный алкенил, необязательно замещенный алкинил, необязательно замещенный арил, необязательно замещенный циклоалкил, необязательно замещенный циклоалкенил, необязательно замещенный гетероарил, необязательно замещенный гетероцикл, ! группу, представленную формулой: -NR5A R6A, где R5A и R6A, каждый независимо, представляет собой водород, гидроксигруппу ...

Способ получения 1-замещенных пиразолонов5 или их солей

Способ получени з-аминопиразолонов-5 или их солей

Гербицидное средство (его варианты)

... 1. Гербицидное средство в форме раствора, содержащее активное вещество-производное пиразола, растворитель и поверхностно-активное ващество , отличающееся тем, что, с целью повышения гербицидной активности, оно содержит активное вещество - производное пиразола общей формулы О а .2 W v тг 1 н где R - водород, ацетил, феноксикарбонил или 3,4-дихлорфеноксикарбонил , R - Cj-С -алкш10кси, С -алкилтио , фенокси, 2-метилфенокси, 3-метоксифенокси, 2-фенилизопропилокси , циклопентилметилокси, циклопен-, тг;лт - О5 циклогексилокси, 2-метт1циклогексилокси , 2-метоксициклогексилокси , R- - метил игги эт.ил, растворитель, выбранньп из группы ксилол, ц- клогексанон, изобутанол, циклогексанол, фракция минерального масла с температурой кипения 210-280 С поверхностно-активное вещество, выбранное из группы продукт присоединения 8-10 моль окиси этилена к 1 моль N-мсноэтаноламида олеиновой кислоты, продукт присоединения 40 моль окКси этилена к 1 моль касторового масла, продукт присоединения о 7 моль окиси этилена ...

Способ получения арилоксипропаноламинов или их фармакологически приемлемых солей (его варианты)

... 1. Способ получения арилокси- пропаноламинов общей формулы I OCH CHCH NHXTSIHA in где R и Rj- одинаковые или различные и являются водородом низшей- алкокси-, циано-, окси- или бен- зилокси- группой; X - разветвленный или неразветвленный алкилен с 2-6 атомами углерода; А - тиофен, пиразолон, хи- ноксалин, хинолин, пиримидин , пурин, пирида- зин, пиримидин-2,4-ди- он, пиримидин-2-тион- 4-он, индазол, хиназолин , тетрагидроакридин, пиразол, пиридин, изо- хинолин, пиразоло ...

Способ получения 1-/2-( -нафтилекси) -этил/-3-метилпиразолена-5

Novel herbicides.

Cyclopropaneamine compound

1-heterocycle substituted diarylamines.

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

Pyrazole derivatives.

This invention relates to the use of pyrazole derivatives of the formula and pharmaceutically acceptable salts and solvates thereof, in the manufacture of a reverse transcriptase inhibitor or modulator, to certain novel such pyrazole derivatives and to processes for the preparation of and compositions containing such novel derivatives.

Family of aryl, heteroaryl, O-aryl and O-heteroaryl carbasugars

Family of aryl, heteroaryl, O-aryl and O-heteroaryl carbasugars

Method of preparation of new penicillins.

1-Heterocycle substituted diarylamines.

Pyrazole derivatives for treating HIV.

Phosphoric esters of 5 (3) - hydroxypyrazoles.

Cyclopropaneamine compound

Family of aryl, heteroaryl, O-aryl and O-heteroaryl carbasugars

Family of aryl, heteroaryl, O-aryl and O-heteroaryl carbasugars

Cyclopropaneamine compound

Pyrazole derivatives

Pyrazole derivatives

Novel herbicides.

INSECTICIDE MEANS

INSECTICIDE MEANS

DIHALOGENPROPEN CONNECTIONS, PROCEDURES FOR THEIR PRODUCTION, IT CONTAINING MEANS AND YOUR USE AS PESTICIDES

INHIBITORS THE NON--NUCLEOSIDE INHIBITORS THAT REVERSEN TRANSKRIPTASE

SUBSTITUTED 2,5-DIHYDRO-3H-PYRAZOL-Ä4,3-CÜPYRIDAZIN-3-ON-DERIVATE, YOUR PRODUCTION AND YOUR USE AS CANNIBINOID-CB1REZEPTORLIGANDEN

SUBSTITUTED PHENYL SULFAMOYL CARBOXAMIDE ONE

VERFAHREN ZUR HERSTELLUNG VON NEUEN PYRAZOLDERIVATEN

VERFAHREN ZUR HERSTELLUNG VON NEUEN PYRAZOL- DERIVATEN

SUBSTITUTED ANILIDDERIVATE, THEIR INTERMEDIATE PRODUCTS, CHEMICALS FOR THE AGRICULTURE AND THE HORTICULTURE AND THEIR USE

N ((3-BENZYL) - 2,2 (UNTIL PHENYL) - PROPAN-1AMINDERIVATE AS CETP HEMMER FOR the TREATMENT OF ATHEROSKLEROSE AND HEART CYCLE ILLNESSES

PROCEDURE FOR the PRODUCTION of a 5-ALKOXY-4HYDROXYMETHYLPYRAZOLVERBINDUNG

INSECTICIDE MEANS

PROCEDURE FOR THE PRODUCTION OF NEW PYRAZOLDERIVATEN

PROCEDURE FOR the PRODUCTION OF NEW ONE 1-ACYL-2 - CYANAZIRIDINEN AND THEIR SALTS AND OPTICAL ISOMERS

PROCEDURE FOR the PRODUCTION of the NEW ONE 1 (4 ' - HYDROXY-6' METHYL-PYRIMIDIN-2' YL) - 3-METHYL-PYRAZOLIN-5-ONS

PROCEDURE FOR THE PRODUCTION OF NEW PYRAZOL DERIVATIVES

PROCEDURE FOR THE PRODUCTION OF N-PHENYLPYRAZOL-1 CARBOXAMIDEN

INSECTICIDE MEANS

N (1,2-AZOLYL) ALKYL CHLORACETANILIDE ONES, PROCEDURE FOR YOUR PRODUCTION AS WELL AS YOUR USE AS HERBICIDES.

PYRAZOLAETHERDERIVATE, PROCEDURE FOR YOUR PRODUCTION AND HERBICIDES, THESE CONNECTIONS CONTAINING

AMINO ALKOXY PYRAZOLE ONE, PROCEDURE FOR YOUR PRODUCTION AND THESE CONTAINING DRUGS.

PROCEDURE FOR THE PRODUCTION OF NEW PENICILLINEN

TRISUBSTITUTED PHENYLDERIVATE AS PHOSPHODIESTERASEINHIBITOREN

TRIAZOLYLOXYBENZYL MORE ALKOXYACRYLSÄUREESTER, PROCEDURES FOR YOUR PRODUCTION AND YOUR USE

Insecticide means

SUBSTITUTED BENZOYLCYCLOHEXANDIONE

SUBSTITUTED BENZOYLKETONE, PROCEDURES FOR YOUR PRODUCTION AND YOUR USE AS HERBICIDES

4 (ARYLAMINOMETHYLEN) - 2,4-DIHYDRO-PYRAZOL-3-ONE

SUBSTITUTED 4-BENZOYL-PYRAZOLE

PROCEDURE FOR the PRODUCTION OF 1-SUBSTITUIERTEN 5 - OR 3-HYDROXY-PYRAZOLEN

Phenyl acetic acid derivatives, process and intermediate products for their production and their use as parasiticides and fungicides

Compounded herbicidal composition containing Shuangzuocaotong and method of using the same

Provided are a compounded weeding composition containing dicarfentrazone-ethyl, and a using method therefor. The compounded weeding composition comprises an active component A and an active component B, the active component A is dicarfentrazone-ethyl and the active component B is glyphosate or glufosinate, the weight proportion between the active component A and the active component B is 1:100-1 and preferentially 1:60-1. The compounded weeding composition has synergistic effects, and has very good activity on preventing resistance weeds.

Inhibitors of cGAS activity as therapeutic agents

This disclosure relates to compounds, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating or preventing inappropriate activation of a type I interferon (IFN) response in a subject in need thereof.

Novel fungicidal heterocyclic compounds

The present invention relates to a compound selected from Formula I and a process for preparing same, wherein R ...

Substituted 3-aryl-pyrazoles

HERBICIDAL 4-BENZOYL-1-ALKYL ALKENYL -PYRAZOLES

3-heterocyclyl-substituted benzoyl derivatives

PREVENTIVE AND/OR THERAPEUTIC DRUGS FOR INFLAMMATORY INTESTINAL DISEASES

4-(4-trifluoromethyl-3-thiobenzoyl)pyrazoles, and use thereof as herbicides

Disclosed are 4-(4-trifluoromethyl-3-thiobenzoyl)pyrazoles of general formula (I) as well as the use thereof as herbicides. In said formula (I), R, R, R, and R represent radicals such as hydrogen and organic radicals such as alkyl, and Y represents hydrogen or a protective group such as tosyl.

Process for production of 5-alkoxy-4-hydroxymethylpyrazole compound

Disclosed is a process for production of a 5-alkoxy-4-hydroxymethylpyrazole compound with good efficiency in a simple manner. A process for production of a 5-alkoxy-4-hydroxymethylpyrazole compound represented by the general formula (3): (3) [wherein R represents a substituent such as an alkyl group and an aryl group which may have a substituent; R represents an electron-withdrawing group; and R represents a substituent such as an alkyl group which may have a substituent] comprises the step of reacting a pyrazole compound represented by the general formula (1): (1) [wherein R and R are as defined above] with a compound represented by the general formula (2): L-R (2) [wherein L represents a leaving group; and R is as defined above] in the presence of a base and formaldehyde.

Process for the preparation of 1-aryl-pyrazol-3-one intermediates useful in the synthesis of sigma receptors inhibitors

The invention relates to a process for preparing 1-aryl-pyrazol-3-one intermediates, tautomers, and salts thereof, to novel intermediates, and to the use of the intermediates in the preparation of sigma receptor inhibitors.

Substituted aminobutyric derivatives as neprilysin inhibitors

In one aspect, the invention relates to compounds having the formula: (I) where R ...

4-thiocarbamoyl-1-(3-pyrazolyl)-pyrazoles and their use as herbicides

MEDICAMENTS

PREVENTIVE AND/OR THERAPEUTIC AGENT FOR CARDIAC DISORDER

Pyrazolone derivatives

SUBSTITUTED ANILIDE DERIVATIVES, INTERMEDIATES THEREOF, AGRICULTURAL AND HORTICULTURAL CHEMICALS, AND THEIR USAGE

Herbicidal substituted benzoylpyrazoles

BENZOYL COMPOUNDS HAVING IMINO GROUP AND HERBICIDES

Neprilysin inhibitors

In one aspect, the invention relates to compounds having the formula XII: where R ...

Small molecule inhibitors of the pleckstrin homology domain and methods for using same

Small molecule inhibitors of the pleckstrin homology domain and methods for using same

Pleckstrin homology domain binding compounds, pharmaceutical compositions including such compounds, and methods for their use are described herein.

Method of treating contrast-induced nephropathy

The present invention provides the use of a neutral endopeptidase inhibitor, in the manufacture of a medicament for the treatment, amelioration and/or prevention of contrast-induced nephropathy. The invention also relates to the use of a compound of Formula (I) wherein R ...

Plant disease-controlling agent

Hyperlipemia remedy

N,N-DIMETHYL-CARBAMIC ACID O-PYRAZOLYL ESTERS

Pyrazole compound or salt thereof, and preparation method, herbicide composition and use thereof

The invention belongs to the technical field of pesticides, and in particular relates to a pyrazole compound or a salt thereof, and a preparation method, a herbicide composition and a use thereof. Disclosed is a pyrazole compound of formula (I) or a salt thereof. In the formula (I), R ...

Substituted 3-aryl-pyrazoles

Synthesis of enone intermediate

The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The recent development of a modular synthesis of tetracycline analogs through a chiral enone intermediate has allowed for the efficient synthesis of novel tetracycline analogs never prepared before. The present invention provides a more efficient route for preparing the enone intermediate.

Compounds, Compositions and Methods for Modulating Uric Acid Levels

Described herein are compounds useful in the reduction 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.

PYRAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY

Compounds of formula (I), pharmaceutical compositions comprising compounds of formula (I) and methods of inhibiting Hsp90 in a cell, treating or preventing a proliferation disorder in a mammal and treating cancer in a mammal comprising administering a compound of formula (I) to a patient or a cell. 179-. (canceled)81. The compound of claim 80 , wherein Ris an optionally substituted phenyl group.82. The compound of claim 81 , wherein Ris substituted with one or more group represented by R claim 81 , wherein R claim 81 , for each occurrence claim 81 , are independently an optionally substituted alkyl claim 81 , an optionally substituted alkenyl claim 81 , an optionally substituted alkynyl claim 81 , an optionally substituted cycloalkyl claim 81 , an optionally substituted cycloalkenyl claim 81 , an optionally substituted heterocyclyl claim 81 , an optionally substituted aryl claim 81 , an optionally substituted heteroaryl claim 81 , an optionally substituted aralkyl claim 81 , an optionally substituted heteraralkyl claim 81 , halo claim 81 , cyano claim 81 , nitro claim 81 , guanadino claim 81 , a haloalkyl claim 81 , a heteroalkyl claim 81 , alkoxy claim 81 , haloalkoxy claim 81 , —NRR claim 81 , —OR claim 81 , —C(O)R claim 81 , —C(O)OR claim 81 , —C(S)R claim 81 , —C(O)SR claim 81 , —C(S)SR claim 81 , —C(S)OR claim 81 , —C(S)NRR claim 81 , —C(NR)OR claim 81 , —C(NR)R claim 81 , —C(NR)NRR claim 81 , —C(NR)SR claim 81 , —OC(O)R claim 81 , —OC(O)OR claim 81 , —OC(S)OR claim 81 , —OC(NR)OR claim 81 , —SC(O)R claim 81 , —SC(O)OR claim 81 , —SC(NR)OR claim 81 , —OC(S)R claim 81 , —SC(S)R claim 81 , —SC(S)OR claim 81 , —OC(O)NRR claim 81 , —OC(S)NRR claim 81 , —OC(NR)NRR claim 81 , —SC(O)NRR claim 81 , —SC(NR)NRR claim 81 , —SC(S)NRR claim 81 , —OC(NR)R claim 81 , —SC(NR)R claim 81 , —C(O)NRR claim 81 , —NRC(O)R claim 81 , —NRC(S)R claim 81 , —NRC(S)OR claim 81 , —NRC(NR)R claim 81 , —NRC(O)OR claim 81 , —NRC(NR)OR claim 81 , —NRC(O)NRR claim 81 , —NRC(S)NRR claim 81 , — ...

PYRAZOLE COMPOUND

The present invention relates to a novel serotonin reuptake inhibitor which also exhibits 5-HTantagonistic action (antidepressive and anxiolytic effects), in particular, 5-HTinverse agonistic action comprising Compound (1): 2. The compound of or a pharmaceutically acceptable salt thereof wherein{'sup': 1', '2', '3, 'R, Rand Rare independently selected from the group consisting of hydrogen atom and methyl group, and'}{'sup': '4', 'Ris hydrogen atom.'}3. The compound of or a pharmaceutically acceptable salt thereof wherein A is an optionally-substituted Caryl group.4. The compound of or a pharmaceutically acceptable salt thereof wherein X is hydrogen atom.5. The compound of or a pharmaceutically acceptable salt thereof wherein L is oxygen atom.6. The compound of or a pharmaceutically acceptable salt thereof wherein n is 1.7. The compound of or a pharmaceutically acceptable salt thereof wherein{'sup': 1', '3', '4, 'R, Rand Rare hydrogen atom, and'}{'sup': '2', 'Ris methyl group.'}8. The compound of or a pharmaceutically acceptable salt thereof wherein R claim 1 , R claim 1 , Rand Rare hydrogen atom.9. The compound of or a pharmaceutically acceptable salt thereof wherein E is an optionally-substituted Ccycloalkyl group claim 1 , an optionally-substituted 5- to 10-membered saturated heterocyclic group which comprises 1 to 3 oxygen atoms as a constituent atom of the ring claim 1 , or an optionally-substituted phenyl group.10. The compound of or a pharmaceutically acceptable salt thereof wherein E is an optionally-substituted Ccycloalkyl group.11. The compound of or a pharmaceutically acceptable salt thereof wherein r is 1 or 2.12. The compound of or a pharmaceutically acceptable salt thereof wherein Ris an optionally-substituted Calkyl group.13. The compound of wherein the compound of Formula (1) is any one of the following compounds claim 1 , or a pharmaceutically acceptable salt thereof:1-[5-(benzyloxy)-1-(cyclohexylmethyl)-1H-pyrazol-3-yl]-N-methylmethanamine;1-{1-( ...

Ethinyl-pyrazole derivative

Provided is a novel compound represented by formula [I] or a pharmaceutically acceptable salt thereof having antagonistic activity against group II metabolism-type glutamic acid (m-Glu) receptors. The compound or pharmaceutically acceptable salt thereof is useful as a prophylactic or therapeutic agent for diseases such as new mood disorders (depressive and bipolar disorders), anxiety disorders (generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, post-traumatic stress disorder, specific phobias, and acute stress disorder), schizophrenia, Alzheimer's disease, cognitive dysfunction, dementia, drug dependence, convulsions, tremors, pain, sleep disorders, and the like.

Process for Preparing 1-phenylpyrazoles

The present invention to a process for preparing 1-phenylpyrazoles of the formula I 2. The compound of claim 1 , wherein m is 0.3. The compound of claim 1 , wherein p is 0 or 1.4. The compound of claim 1 , wherein p is 1 and Ris located meta or para to the attachment point of the methylene bridge.5. The compound of claim 1 , wherein Ris chlorine claim 1 , fluorine claim 1 , C-C-alkyl or C-C-haloalkyl.6. The compound of claim 1 , wherein Ris methoxy claim 1 , halomethoxy or benzyloxy.7. The compound of claim 1 , wherein Ris methyl or halomethyl.8. The compound of claim 1 , wherein Y is nitro or a group R.9. The compound of claim 1 , wherein Y is nitro or a group Rand wherein m is 0 and p is 0. This application is a continuation of U.S. application Ser. No. 13/393,624, filed Mar. 1, 2012, which application is a national stage application of International Application No. PCT/EP2010/062950, filed Sep. 3, 2010, the entire contents of which is hereby incorporated herein by reference. This application also claims priority under 35 U.S.C. §119 to European Patent Application No. 09169528.8 filed Sep. 4, 2009, the entire contents of which is hereby incorporated herein by reference.The present invention relates to a process for preparing 1-phenylpyrazoles. In particular, the invention relates to a process for preparing 1-phenylpyrazoles by C—N coupling of a phenyl halide and a pyrazole compound.1-Phenylpyrazols are of great interest especially as pharmaceutical and pesticide pharmacophors, and as precursors of such active ingredients. Pyraclostrobine is a prominent representative of a pesticidal N-phenylpyrazole derivative.The most important method for preparing this class of heterocycles involves the double condensation of 1,3-diketones with phenyl hydrazine or its derivatives. This method has a wide scope not only because of the readily availability of 1,3-diketones but also because one carbonyl of the diketone starting material can be replaced by an acetal, a hemiacetal, a ...

COMPOUNDS ACTING AT MULTIPLE PROSTAGLANDIN RECEPTORS GIVING A GENERAL ANTI-INFLAMMATORY RESPONSE

The present invention provides a compound that is represented by the following general formula 1. A compound , that is a -[(2-{(hydrocarbyl or substituted hydrocarbyl)oxa , thia , sulfinyl , sulfonyl or alkylenyl}phenyl)methyl]-(5-hydro or alkyl or fluoroalkyl)-1H-pyrazole-3-(oxaacetic acid or azaacetic acid or thiaacetic acid) or an alkyl or aryl ester or sulfonamide thereof2. The compound of claim 1 , that is a 1-[(2-{(hydrocarbyl)oxa}phenyl)methyl]-(5-alkyl)-1H-pyrazole-3-(oxaacetic acid) or an alkyl or aryl ester or sulfonamide thereof3. The compound of claim 1 , wherein said hydrocarbyl is selected from the group consisting of alkyl and carbocyclic aryl.4. The compound of claim 3 , wherein said hydrocarbyl is selected from the group consisting of branched chain alkyl and phenyl.5. The compound of claim 4 , wherein said hydrocarbyl is selected from the group consisting of branched chain alkyl having from 4 to 7 carbons.6. The compound of claim 1 , wherein said compound is a 1H-pyrazole-3-oxaacetic acid compound or lower alkyl ester thereof.7. The compound of claim 6 , wherein said compound is a 5-alkyl-1H-pyrazole.8. The compound of claim 6 , wherein said phenyl is a bromophenyl.9. The compound of claim 1 , wherein said compound is a 5-alkyl-1H-pyrazole-3-oxaacetic acid compound or lower alkyl ester thereof claim 1 , said hydrocarbyl is selected from the group consisting of branched chain alkyls having from 4 to 7 carbons and said phenyl is a bromophenyl.10. The compound of claim 1 , that is selected from the group consisting of:{1-[5-Chloro-2-(2-ethyl-butoxy)-benzyl]-5-methyl-1H-pyrazol-3-yloxy}-acetic acid;{1-[5-Chloro-2-(4-chloro-benzyloxy)-benzyl]-5-methyl-1H-pyrazol-3-yloxy}-acetic acid;{1-[5-Bromo-2-(2-ethyl-butoxy)-benzyl]-5-methyl-1H-pyrazol-3-yloxy}-acetic acid; and,{1-(5-Chloro-2-isobutoxy-benzyl)-5 -methyl-1H-pyrazol-3-yloxy}-acetic acid.12. The compound of claim 11 , wherein Ris selected from the group consisting of carbocyclic aryl and alkyl.13. The ...

PHARMACEUTICAL COMPOSITION

The present invention provides compounds of Formula I: 3. The compound of claim 2 , wherein Ris hydrogen; or a pharmaceutically acceptable salt thereof.4. The compound of claim 3 , wherein Ris selected from chloro claim 3 , trifluoromethyl claim 3 , difluoromethyl claim 3 , difluoromethoxy claim 3 , and trifluoromethoxy; or a pharmaceutically acceptable salt thereof.18. A method of treating multiple sclerosis in a mammal claim 10 , comprising the step of administering to the mammal a pharmaceutical composition comprising a compound of claim 10 , or a pharmaceutically acceptable salt thereof.22. A method of treating rheumatoid arthritis in a mammal claim 10 , comprising the step of administering to the mammal a pharmaceutical composition comprising a compound of claim 10 , or a pharmaceutically acceptable salt thereof. This application is a continuation of PCT/US11/51163, filed Sep. 12, 2011, which application claims the benefit of U.S. Provisional Patent Application No. 61/384,781, filed Sep. 21, 2010, the disclosures of each of which are incorporated by reference herein in their entireties.Upon encountering antigen, naive CD4+ T helper precursor (Thp) cells are differentiated into two distinct subsets, Type 1 T helper (Th1) and Type 2 T helper (Th2). Recently, a novel T cell subset, the Th17 cells, has also been identified and characterized. These differentiated Th cells are defined both by their distinct functional abilities and by unique cytokine profiles. Specifically, Th1 cells produce interferon-gamma, interleukin (IL)-2, and tumor necrosis factor (TNF)-beta, which activate macrophages and are responsible for cell-mediated immunity and phagocyte-dependent protective responses. In contrast, Th2 cells are known to produce IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13, which are responsible for strong antibody production, eosinophil activation, and inhibition of several macrophage functions, thus providing phagocyte-independent protective responses. Th17 cells mainly ...

PYRAZOLE COMPOUNDS HAVING THERAPEUTIC EFFECT ON MULTIPLE MYELOMA

Novel therapeutic agents for myeloma are provided. 2. The pyrazole compound according to claim 1 , a tautomer of the compound claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein X is —(CR claim 1 , R).3. The pyrazole compound according to claim 2 , a tautomer of the compound claim 2 , or a pharmaceutically acceptable salt or solvate thereof claim 2 , wherein Ris C-Calkyl claim 2 , C-Calkyl substituted with R claim 2 , C-Chaloalkyl claim 2 , C-Ccycloalkyl claim 2 , —C(O)R claim 2 , —C(O)OR claim 2 , —C(O)N(R)R claim 2 , —C(R)═NR claim 2 , —C(R)═NOR claim 2 , D1 to D12 claim 2 , D18 claim 2 , D19 claim 2 , D21 to D23 claim 2 , phenyl or phenyl substituted with (R)a claim 2 ,{'sup': 11', '11', '11, 'sub': 2', '2', '2, "in which when there are two neighboring R, the two neighboring Rmay form —OCHO—, —OCHCHO—, —OCH═CH—, —CH═CHCH═CH— or —N═CHCH═CH— to form, together with the carbon atoms attached to the two R, a 5-membered or 6-membered ring which may have a hydrogen atom on the ring-constituting carbon atoms optionally replaced by a Z which may be identical with or different from one another, if two or more Z's are present,"}{'sup': 2', '12', '12', '21', '21, 'sub': 1', '6', '3', '6', 'e', 'e, 'Ris a hydrogen atom, a halogen atom, C-Calkyl, C-Ccycloalkyl, D1, D2, D4 to D12, D18, D19, D21 to D23, —C(O)R, —C(O)OR, benzyl, benzyl having a benzene ring optionally substituted with (R), phenyl or phenyl optionally substituted with (R),'}{'sup': 21', '21', '21, 'sub': 2', '2', '2, "in which when there are two neighboring R, the two neighboring Rmay form —OCHO—, —OCHCHO—, —OCH═CH— or —CH═CHCH═CH— to form, together with the carbon atoms attached to the two R, a 5-membered or 6-membered ring which may have a hydrogen atom on the ring-constituting carbon atoms replaced by one or more Z's which may be identical with or different from one another, if two or more Z's are present,"}{'sup': 3', '12', '12', '12', '13', '32', '33', '34', '15, 'sub': 1', '4 ...

FUNGICIDAL N-(2-PHENOXYETHYL)CARBOXAMIDE DERIVATIVES AND THEIR AZA, THIA AND SILA ANALOGUES

The present invention relates to fungicide N-(2-phenoxyethyl)carboxamide derivatives of formula (I), their aza, thia and sila analogues, their process of preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions. Formula (1) wherein A, T, W, X, n and Zto Zrepresent various substituents. 3. A compound according to wherein A is selected in the list consisting of A; A; Aand A.4. A compound according to wherein A represents Aand wherein Rrepresents a C-C-alkyl claim 3 , C-C-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; or C-C-alkoxy; Rrepresents a hydrogen atom or a halogen atom; Rrepresents a C-C-alkyl.5. A compound according to wherein W represents O or S.6. A compound according to wherein n represents 0 claim 1 , 1 or 2.7. A compound according to wherein X independently represents a halogen atom; C-C-alkyl; C-C-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; tri(C-C-alkyl)silyl; C-Calkoxy or C-C-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different or wherein two consecutive substituents X together with the phenyl ring form a substituted or non substituted 1 claim 1 ,3-benzodioxolyl; 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-quinoxalinyl; 3 claim 1 ,4-dihydro-2H-1 claim 1 ,4-benzoxazinyl; 1 claim 1 ,4-benzodioxanyl; indanyl; 2 claim 1 ,3-dihydrobenzofuranyl; or indolinyl.8. A compound according to wherein Zand Zindependently represent a C-C-alkyl.9. A compound according to wherein Zand Zindependently represent a hydrogen atom or a C-C-alkyl.10. A compound according to wherein Zand Zindependently represent a hydrogen atom or a C-C-alkyl.11. A compound according to wherein Zrepresents a C-Ccycloalkyl substituted by up to 10 groups or atoms that can be the same or different and that can be selected in the list consisting of halogen ...

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- ...

METHOD FOR PRODUCING PYRAZOLE CARBOXYLIC ACID DERIVATIVE

Disclosed is a process for producing a pyrazole carboxylic acid derivative which is useful as a significant intermediate of an 11βHSD-1 inhibitor. 2. The process according to claim 1 , wherein the halogenating agent is N-halogenosuccinimide claim 1 , N-halogenoacetamide or halogen.3. The process according to claim 2 , wherein the halogenating agent is N-bromosuccinimide claim 2 , N-bromoacetamide claim 2 , N-chlorosuccinimide or I.4. The process according to claim 1 , wherein the reaction is performed in the presence of a Lewis acid.5. The process according to claim 4 , wherein the Lewis acid is boron trifluoride ether complex or metal halide.6. The process according to claim 5 , wherein the Lewis acid is boron trifluoride n-butyl ether complex claim 5 , boron trifluoride diethyl ether complex or SnCl4.8. The process according to claim 7 , wherein the base is an organic base.11. The process according to claim 10 , wherein the base is a metal alkoxide.17. The process according to claim 16 , wherein the halogenating agent is selected from phosphorus oxyhalide claim 16 , phosphorus pentahalide claim 16 , oxalyl halide and thionyl halide.26. The process according to claim 1 , wherein Rand Rare substituted or unsubstituted alkyl.27. The process according to claim 1 , wherein Ris substituted or unsubstituted alkyl.28. The process according to claim 1 , wherein Rand Rare the same substituted or unsubstituted alkyl.31. The process according to claim 30 , wherein the reaction is performed in the presence of a condensing agent.32. The process according to claim 31 , wherein the condensing agent is one or more condensing agent(s) selected from N claim 31 ,N′-dicyclohexylcarbodiimide claim 31 , N claim 31 ,N′-diisopropylcarbodiimide and 1-ethyl-3-(3-dimethylamino propyl)carbodiimide hydrochloride.33. The process according to claim 31 , wherein the reaction is performed in the presence of one or more additive agent(s) selected from 1-hydroxybenzotriazole and N-hydroxy ...

PYRAZOLE COMPOUND

The present invention relates to a novel serotonin reuptake inhibitor which also exhibits 5-HTantagonistic action (antidepressive and anxiolytic effects), in particular, 5-HTinverse agonistic action comprising Compound (1): 117-. (canceled)19. The method of wherein the disease is (i) depression or (ii) anxiety.20. The method of wherein the disease is (i) depressive disorders such as major depressive disorder claim 18 , dysthymic disorder claim 18 , and depressive disorders not otherwise specified claim 18 , (ii) depression claim 18 , (iii) seasonal affective disorder claim 18 , or (iv) major depressive episode in bipolar disorder.21. The method of wherein the disease is (i) panic disorder claim 18 , (ii) obsessive-compulsive disorder claim 18 , (iii) posttraumatic stress disorder claim 18 , (iv) acute stress disorder claim 18 , (v) generalized anxiety disorder claim 18 , (vi) anxiety disorder due to a general medical condition claim 18 , (vii) anxiety disorder comprising substance-induced anxiety disorder claim 18 , (viii) agoraphobia claim 18 , (ix) social phobia claim 18 , (x) avoidant personality disorder claim 18 , or (xi) psychophysiological disorder.22. The method of wherein the disease is a symptom of depression or anxiety associated with schizophrenia or dementia.23. The method of wherein the disease is (i) memory impairment claim 18 , (ii) eating behavior disorder claim 18 , (iii) obesity claim 18 , (iv) sleep disorder claim 18 , (v) schizophrenia claim 18 , (vi) addiction to drugs claim 18 , (vii) cluster headache claim 18 , (viii) migraine claim 18 , (ix) pain claim 18 , (x) Alzheimer's disease claim 18 , (xi) chronic paroxysmal hemicrania claim 18 , (xii) headache associated with vascular disorder claim 18 , (xiii) Parkinson's disease claim 18 , (xiv) endocrine abnormality claim 18 , (xv) vasospasm claim 18 , (xvi) hypertension claim 18 , (xvii) gastrointestinal disorder associated with motility and secretory change claim 18 , or (xviii) sexual ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 6. The compound of claim 5 , where Ris selected from —CH claim 5 , —OCH claim 5 , and Cand Ris H; or Ris selected from H claim 5 , —CH claim 5 , Cl claim 5 , and F claim 5 , and Ris Cl; or Ris H and Ris selected from —CHand —CN; Ris selected from H claim 5 , —Calkyl claim 5 , and —(CH)ORwhere Ris H or —CH; and Ris H.10. The compound of claim 9 , where Ris F claim 9 , Ris Cl claim 9 , Ris H claim 9 , Ris —OCHor —OCHCH claim 9 , and Ris H.14. The compound of claim 13 , where Ris F claim 13 , Ris Cl claim 13 , Ris H claim 13 , and Ris H.17. The compound of claim 16 , where Rand Rare H; Ris selected from —Calkyl claim 16 , —(CH)OR claim 16 , and —(CH)NRR; Ris selected from —OH claim 16 , —OCH claim 16 , —OCHCH claim 16 , and —Calkyl; and Ris H.18. The compound of claim 17 , where Rand Rare H claim 17 , Ris —CH claim 17 , Ris —OH or —OCH claim 17 , and Ris H.20. The compound of claim 19 , where Ris H claim 19 , Ris Cl claim 19 , Ris H claim 19 , —CH claim 19 , —CHCHor —(CH)OH claim 19 , Ris —OH or —OCH claim 19 , and Ris H; or Ris F claim 19 , Ris Cl claim 19 , Ris H or —Calkyl claim 19 , Ris —OH claim 19 , —OCHor —Calkyl claim 19 , and Ris H.22. The compound of claim 21 , where Ris H or F; Ris Cl; Ris H or —Callyl; Ris —OCH claim 21 , —OCHCH claim 21 , or —Calkyl; R claim 21 , if present claim 21 , is H; and Ris H.24. The compound of claim 23 , where Ris F claim 23 , Ris Cl claim 23 , Ris H or —Calkyl claim 23 , R claim 23 , if present claim 23 , is H claim 23 , and Ris H.27. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .28. The pharmaceutical composition of claim 27 , further comprising a therapeutic agent selected from adenosine receptor antagonists claim 27 , α-adrenergic receptor antagonists claim 27 , β-adrenergic receptor antagonists claim 27 , β-adrenergic receptor agonists claim 27 , dual-acting β-adrenergic receptor antagonist/α-receptor ...

Use of alkoxypyrazoles as nitrification inhibitors

The present invention relates to nitrification inhibitors of formula (I), which are alkoxypyrazole compounds. Moreover, the invention relates to the use of compounds of formula (I) as nitrification inhibitors, i.e. for reducing nitrification, as well as agro-chemical mixtures and compositions comprising the nitrification inhibitors of formula (I).

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula XII: 128-. (canceled)29: A compound of:(a) (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester;(b) (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid 2,2,3,3,3-pentafluoropropyl ester;(c) (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo[1,3]dioxol-4-ylmethyl ester; or(d) (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid butyryloxymethyl ester.30: A compound of:(a) (2R,4R)-4-amino-5-(5′-chloro-2′-fluoro-biphenyl-4-yl)-2-hydroxypentanoic acid;(b) (2R,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester;(c) (2R,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester;(d) (2R,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 2,2,3,3,3-pentafluoropropyl ester; or(e) (2R,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid butyryloxymethyl ester.31: A compound of:(a) (3R,5R)-5-(3′-Chlorobiphenyl-4-ylmethyl)-1-(2,2-dimethylpropionyl)-3-hydroxypyrrolidin-2-one; or(b) (2R,4R)-4-t-butoxycarbonylamino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid.32: A compound of:(a) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic acid ethyl ester;(b) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-{[5-(4-methoxybenzyloxy)-1-methyl-1H-pyrazole-3-carbonyl]amino}pentanoic acid; or(c) (2R,4R)-4-amino-5-biphenyl-4-yl-2-hydroxypentanoic acid ethyl ester. 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.1. Field of the InventionThe present invention relates to novel compounds which are metabolized in vivo to compounds having activity as neprilysin ...

SMALL MOLECULE INHIBITORS OF LACTATE DEHYDROGENASE AND METHODS OF USE THEREOF

Provided is a compound of formula (I) 2. The compound or salt of claim 1 , wherein Ris hydrogen claim 1 , substituted or unsubstituted C-Calkyl claim 1 , substituted or unsubstituted C-Calkenyl claim 1 , substituted or unsubstituted C-Calkynyl claim 1 , substituted or unsubstituted C-Ccycloalkyl claim 1 , substituted or unsubstituted C-Ccycloalkylalkyl claim 1 , substituted or unsubstituted aryl claim 1 , substituted or unsubstituted arylalkyl claim 1 , hydroxyl claim 1 , hydroxyalkyl claim 1 , halo claim 1 , C-Chaloalkyl claim 1 , —CN claim 1 , cyanoalkyl claim 1 , —NRR claim 1 , or substituted or unsubstituted heteroarylalkyl.3. The compound or salt of claim 2 , wherein Ris substituted or unsubstituted C-Calkyl claim 2 , substituted or unsubstituted cyclopropyl claim 2 , substituted or unsubstituted —(C-Calkyl)-cyclopropyl claim 2 , substituted or unsubstituted —CH═CH claim 2 , substituted or unsubstituted —C≡C-cyclopropyl claim 2 , substituted or unsubstituted phenyl claim 2 , substituted or unsubstituted benzyl claim 2 , —OH claim 2 , —CHOH claim 2 , —CF claim 2 , —CFCF claim 2 , —Cl claim 2 , —F claim 2 , —I claim 2 , —CN claim 2 , —CHCN claim 2 , —NH claim 2 , or —CH-tetrazolyl.4. The compound or salt of claim 1 , wherein Ris —COH or —CO(C-Calkyl) claim 1 , wherein the C-Calkyl is substituted or unsubstituted.5. The compound or salt of claim 1 , wherein Rand Rare the same or different and each is H or C-Calkyl.6. The compound or salt of claim 1 , wherein each Ris independently halo claim 1 , C-Chaloalkyl claim 1 , C-Chaloalkoxy claim 1 , substituted or unsubstituted C-Calkyl claim 1 , substituted or unsubstituted C-Calkenyl claim 1 , substituted or unsubstituted C-Calkynyl claim 1 , substituted or unsubstituted —(CH)aryl claim 1 , substituted or unsubstituted —(CH)heteroaryl claim 1 , or substituted or unsubstituted —(CH)heterocycloalkyl.7. The compound or salt of claim 1 , wherein m is 0 claim 1 , 1 claim 1 , or 2.8. The compound or salt of claim 1 , wherein ...

FUNGICIDAL PYRAZOLES

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, 2. A compound of wherein:{'sup': 1', '3', '3', '3, 'Qis phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R; provided that when an Rsubstituent is located at a meta position, then said Rsubstituent is selected from F, Cl, Br and cyano;'}{'sup': 2', '3', '3', '3, 'Qis phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1, 2 or 3 substituents independently selected from R, provided that when an Rsubstituent is located at a meta position, then said Rsubstituent is selected from F, Cl, Br and cyano;'}{'sup': 4', '15', '16, 'X is O, NR, C(═O) or CRR;'}{'sup': 1', '5', '6', '7, 'sub': 1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '5, 'Ris H, halogen, C-Calkyl, C-Chaloalkyl, COR, C(O)NRR, cyano, C-Calkoxy, C-Chaloalkoxy or C-Calkoxyalkyl;'}{'sup': '1a', 'Ris H;'}{'sup': '2', 'sub': 3', '2', '3, 'Ris CH, CHCH, Cl or Br;'}{'sup': '3', 'sub': 1', '4', '1', '4', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '3', '4', '2, 'each Ris independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C-Calkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy C-Calkylthio, C-Chaloalkylthio, C-Calkylsulfinyl, C-Chaloalkylsulfinyl, C-Calkylsulfonyl, C-Chaloalkylsulfonyl, C-Ccycloalkyl, C(═S))NHand —U—V-T;'}{'sup': 4', '10', '12, 'sub': 3', '7', '1', '6', '1', '6, 'Ris H, formyl, C-Ccycloalkyl or —SR; or C-Calkyl or C-Chaloalkyl, each optionally substituted with up to 2 R;'}{'sup': '5', 'sub': 1', '6, 'Ris C-Calkyl;'}{'sup': '6', 'sub': 1', '6, 'Ris H or C-Calkyl;'}{'sup': '7', 'sub': 1', '6', '1', '6', '4', '8, 'Ris H, C-Calkyl, C-Chaloalkyl or C-Calkylcycloalkyl; or'}{'sup': 6', '7', '13, 'Rand Rare taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic ...

COMPOUNDS USEFUL AS MODULATORS OF TRPM8

The present invention includes compounds useful as modulators of TRPM8, such as compounds of Formulae (Ia), (Ib) and (Ic), and the subgenus and species thereof; personal products containing those compounds; and the use of those compounds and the personal products, particularly the use of increasing or inducing chemesthetic sensations, such as cooling or cold sensations. 2. The compound of claim 1 , wherein either Ror Ris C-Calkyl claim 1 , and the remaining Ror Ris selected from the group consisting of optionally substituted alkyl claim 1 , optionally substituted alkenyl claim 1 , optionally substituted alkynyl claim 1 , optionally substituted alkylaryl claim 1 , optionally substituted heteroalkyl claim 1 , optionally substituted carbocyclyl claim 1 , and optionally substituted heterocyclyl; or alternatively claim 1 , Rand R claim 1 , taken together with the atoms to which they are attached claim 1 , form an optionally substituted carbocyclic ring;{'sup': '1', 'X and Xare N;'}{'sup': 8', '9', '9', '9', '9, 'Ris selected from the group consisting of -alkylene-carbonyl-aryl, -alkylene-carbonyl-heteroaryl, -alkylene-carbonyl-(substituted aryl), -alkylene-carbonyl-(substituted heteroaryl), -alkylene-carbonyl-O-aryl, -alkylene-carbonyl-O-(substituted aryl), -alkylene-carbonyl-NR-aryl, -alkylene-carbonyl-NR-(substituted aryl), -alkylene-carbonyl-O-heteroaryl, -alkylene-carbonyl-O-(substituted heteroaryl), -alkylene-carbonyl-NR-heteroaryl, and -alkylene-carbonyl-NR-(substituted heteroaryl);'}{'sup': '9', 'Ris selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted acylamido, and optionally substituted diacylamido;'}A is O;{'sub': '2', 'B is CH, or C═O; and'}C is a covalent bond.4. The compound of claim 3 , wherein{'sup': 5', '6', '5', '6', '5', '6, 'sub': 1 ...

Treatment of Amyotrophic Lateral Sclerosis

The present invention relates to the identification of compounds and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided 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 ...

PYRAZOLE DERIVATIVES AND THEIR USES THEREOF

The present disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof; wherein U, R1, R2, R3 and Q are as defined herein. The disclosure also provides a method for treating or preventing a method for the prevention, treatment and/or alleviation of one or more autoimmune or alloimmune disease, pharmaceutical compositions and combination comprising a therapeutically effective amount of a compound, as defined herein. 2. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R2 is H.3. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R1 is H or alkyl.4. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R1 is C1-3 alkyl.5. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R3 is C6-10-aryl claim 1 , —C1-2alkyl-C6-10aryl claim 1 , 5-6 membered heterocycle claim 1 , —C1-2alkyl-5-6 membered heterocycle claim 1 , C5-6-cycloalkyl claim 1 , —C1-2alkyl-C5-6cycloalkyl or C1-6 substituted alkyl.6. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R3 is phenyl claim 1 , CH-phenyl; cyclopentyl; cyclohexyl claim 1 , CH-cyclopentyl; CH-cyclohexyl; CH—COOH or CHCHNH.7. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein U is an alkylene residue of 1-5 members.8. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein U is an alkylene residue of 2-5 members claim 1 , wherein one carbon atom is replaced by O or NR10.9. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein U is CH—CH claim 1 , CH; CH—O claim 1 , O—CH; or CH—NH—CH.10. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein when Q is comprising R4 claim 1 , said R4 is hydroxyl.11. A compound according to having the formula of compound #14 claim 1 , 15 claim 1 , 18 claim 1 , 20 claim 1 , 24 claim 1 , 28 claim 1 , 32 claim 1 , 37 claim 1 , 41 ...

MULTI-TIERED, HIGH THROUGH-PUT SCREEN FOR COMPOUNDS EFFECTIVE AGAINST BACTERIAL BIOFILM COMPOUNDS EFFECTIVE FOR INHIBITING AND ERADICATING BACTERIAL BIOFILM

A high through-put screening method for identifying agents effective for inhibiting biofilm formation and/or killing established biofilm are disclosed. The method includes three tiers, and each tier includes three specific biological process assays. The tier levels are a primary screen, a confirmation screen, and a dose-response screen, and the biological process assays include as says for total bacterial growth, bacterial metabolic activity, and biofilm formation. 1. A high through-put screening method for identifying agents from a library of compounds , said agents effective for inhibiting biofilm formation and/or killing established biofilm , the method comprising: (A) primary screen,', '(B) confirmation screen,', '(C) dose-response screen;, 'conducting three tiers of three assays; the tiers comprising'} (a) total bacterial growth assay', '(b) bacterial metabolic activity assay', '(c) biofilm formation assay,, 'the assays comprising'}wherein the library of compounds is subject to tier A and only compounds meeting a primary parameter advance to tier B, and only tier B compounds meeting a confirmation parameter advance to tier C, and only tier C compounds meeting a dose-response parameter are identified as putative agents effective for inhibiting and/or eradicating a biofilm, further wherein the assays are conducted for each compound subject to the respective tier.2. The high through-put screening method according to claim 1 , wherein the total bacterial growth assay according to (a) comprises optical density measurement claim 1 , the bacterial metabolic activity assay according to (b) comprises resazurin indicator claim 1 , and the biofilm formation assay according to (c) comprises crystal violet staining claim 1 , each assay being conducted in the presence of a concentration of a compound subject to a tier.3. The high through-put screening method according to claim 2 , wherein the primary parameter is one of ≧80% inhibition in (a) claim 2 , ≧80% inhibition in (b) ...

PYRAZOLE DERIVATIVES AND THEIR USES THEREOF

The present disclosure relates to a compound of formula 116-. (canceled)18. The method of claim 17 , wherein the autoimmune disease is at least one of immune thrombocytopenia claim 17 , refractory immune thrombocytopenia claim 17 , autoimmune haemolytic anemia claim 17 , Graves' disease claim 17 , myasthenia gravis claim 17 , bullous pemphigoid claim 17 , pemphigus vulgaris claim 17 , rheumatic fever or Goodpasture's syndrome; and the alloimmune disease is alloantibody-mediated haemolytic transfusion reaction claim 17 , disease of the fetus and newborn or pernicious anemia.19. The method of claim 18 , wherein R2 is H.20. The method of claim 18 , wherein R1 is H or alkyl.21. The method of claim 18 , wherein R3 is C6-10-aryl claim 18 , —C1-2alkyl-C6-10aryl claim 18 , 5-6 membered heterocycle claim 18 , —C1-2alkyl-5-6 membered heterocycle claim 18 , C5-6-cycloalkyl claim 18 , —C1-2alkyl-C5-6cycloalkyl or C1-6 substituted alkyl.22. The method of claim 18 , wherein U is an alkylene residue of 1-5 members or U is an alkylene residue of 2-5 members claim 18 , wherein one carbon atom is replaced by O or NR10.24. The method of claim 23 , wherein R2 is H.25. The method of claim 23 , wherein R1 is H or alkyl.26. The method of claim 23 , wherein R3 is C6-10-aryl claim 23 , —C1-2alkyl-C6-10aryl claim 23 , 5-6 membered heterocycle claim 23 , —C1-2alkyl-5-6 membered heterocycle claim 23 , C5-6-cycloalkyl claim 23 , —C1-2alkyl-C5-6cycloalkyl or C1-6 substituted alkyl.27. The method of claim 23 , wherein U is an alkylene residue of 1-5 members or U is an alkylene residue of 2-5 members claim 23 , wherein one carbon atom is replaced by O or NR10.29. The method of claim 28 , wherein the blood fragment is a platelet.30. The method of claim 28 , wherein the autoantibodies or alloantibodies are IgG antibodies.31. The method of claim 28 , wherein R2 is H.32. The method of claim 28 , wherein R1 is H or alkyl.33. The method of claim 28 , wherein R3 is C6-10-aryl claim 28 , —C1-2alkyl-C6- ...

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

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

USE OF N-FUNCTIONALIZED ALKOXY PYRAZOLE COMPOUNDS AS NITRIFICATION INHIBITORS

The present invention relates to the use of novel nitrification inhibitors of formula (I), which are N-functionalized alkoxy pyrazole compounds. Moreover, the invention relates to the use of compounds of formula (I) as nitrification inhibitors, i.e. for reducing nitrification, as well as agrochemical mixtures and compositions comprising the nitrification inhibitors of formula (I). 2. The compound of claim 1 , wherein Ris C-C-alkyl claim 1 , benzyl claim 1 , allyl.3. The compound of claim 1 , whereinn is 0; or{'sup': '2', 'sub': 1', '3, 'n is 1, and Ris C-C-alkyl or phenyl.'}4. The compound of claim 1 , wherein{'sup': N', 'd', 'a', 'b', 'a', 'b', 'c', 'b', 'b', 'a', 'e', 'f, 'sub': '2', 'Ris (═O)R, CHRC(═O)OR, CHRC(═O)NRR, CH(C(═O)OR)CH(C(═O)OR), or CHRNR(C═O)R.'}5. The compound of claim 1 , wherein{'sup': 'a', 'Ris H;'}{'sup': 'b', 'sub': 1', '4, 'Ris H or C-C-alkyl;'}{'sup': 'c', 'sub': 1', '4, 'Ris H or C-C-alkyl;'}{'sup': 'd', 'sub': 1', '3, 'Ris C-C-alkyl;'}{'sup': 'e', 'Ris H;'}{'sup': 'f', 'sub': '3', 'Ris H or CH.'}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 , comprising treating a plant growing on soil or soil substituents and/or the locus or soil or 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 , wherein the plant and/or the locus or soil or soil substituents where the plant is growing or is intended to grow is additionally provided with a fertilizer.12. The method of claim 11 , wherein the application of said compound of formula I and of said fertilizer is carried out simultaneously or with a time lag.13. A method for treating a fertilizer or a composition claim 1 , ...

Compounds and Methods for Producing a Conjugate

The present disclosure provides conjugate structures and compound structures used to produce these conjugates. The disclosure also encompasses methods of production of such conjugates, as well as methods of using the same. 2. The conjugate of claim 1 , wherein Yis N.3. The conjugate of claim 1 , wherein Yis O.4. The conjugate of claim 1 , wherein Ris alkyl claim 1 , substituted alkyl claim 1 , aryl or substituted aryl.5. The conjugate of claim 1 , wherein Ris methyl claim 1 , t-butyl or aryl.6. The conjugate of claim 1 , wherein the dotted line between the R-carbon and the R-carbon is a double bond claim 1 , n is 1 claim 1 , and Rand Rare not present.7. The conjugate of claim 1 , wherein the dotted line between the R-carbon and the R-carbon is not a double bond claim 1 , n is 1 claim 1 , and Ris hydroxyl.8. The conjugate of claim 1 , wherein n is 2 claim 1 , the dotted line between the R-carbon and the R-carbon is not a double bond and Ris not present.11. The conjugate of claim 1 , wherein the detectable label comprises a fluorophore.12. The conjugate of claim 1 , wherein Wis the drug or the detectable label claim 1 , and Wis the polypeptide.13. The conjugate of claim 1 , wherein Wis the polypeptide claim 1 , and Wis the drug or the detectable label.15. The compound of claim 14 , wherein Ris alkyl claim 14 , substituted alkyl claim 14 , aryl or substituted aryl.16. The compound of claim 14 , wherein Ris methyl claim 14 , t-butyl or aryl.17. The compound of claim 14 , wherein Ris substituted aryl.18. The compound of claim 17 , wherein Ris substituted with one or more groups each independently selected from alkyl claim 17 , substituted alkyl claim 17 , alkoxy claim 17 , substituted alkoxy claim 17 , amino claim 17 , substituted amino claim 17 , carboxyl claim 17 , carboxyl ester claim 17 , amide claim 17 , substituted amide claim 17 , alkylamide claim 17 , substituted alkylamide claim 17 , aryl claim 17 , substituted aryl claim 17 , heteroaryl claim 17 , substituted ...

MODULATOR OF THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR, PHARMACEUTICAL COMPOSITIONS, METHODS OF TREATMENT, AND PROCESS FOR MAKING THE MODULATOR

Compounds of Formula (I): 171.-. (canceled)73. Crystalline Form A according to in substantially pure form.74. Crystalline Form A according to claim 72 , characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 6.6±0.2 claim 72 , 7.6±0.2 claim 72 , 9.6±0.2 claim 72 , 12.4±0.2 claim 72 , 13.1±0.2 claim 72 , 15.2±0.2 claim 72 , 16.4±0.2 claim 72 , 18.2±0.2 claim 72 , and 18.6±0.2.75. Crystalline Form A according to claim 72 , characterized by an X-ray powder diffractograph having a signal at at least three two-theta values chosen from 6.6±0.2 claim 72 , 9.6±0.2 claim 72 , 13.1±0.2 claim 72 , 15.2±0.2 claim 72 , 18.2±0.2 claim 72 , and 18.6±0.2.76. Crystalline Form A according to claim 72 , characterized by an X-ray powder diffractograph having a signal at three two-theta values of 6.6±0.2 claim 72 , 13.1±0.2 claim 72 , 18.2±0.2.77. Crystalline Form A according to claim 72 , characterized by an X-ray powder diffractograph having a signal at six two-theta values of 6.6±0.2 claim 72 , 9.6±0.2 claim 72 , 13.1±0.2 claim 72 , 15.2±0.2 claim 72 , 18.2±0.2 claim 72 , and 18.6±0.2.78. Crystalline Form A according to claim 72 , characterized by an X-ray powder diffractogram substantially similar to that in .79115.-. (canceled)116. A pharmaceutical formulation comprising at least one crystalline form according to and a pharmaceutically acceptable carrier.117125.-. (canceled) Disclosed herein is a modulator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing the modulator, methods of treatment of cystic fibrosis, and a process for making the modulator.Cystic fibrosis (CF) is a recessive genetic disease that affects approximately 70,000 children and adults worldwide. Despite progress in the treatment of CF, there is no cure.In patients with CF, mutations in CFTR endogenously expressed in respiratory epithelia lead to reduced apical anion secretion causing an imbalance in ion and ...

Novel compounds

The present invention relates to compounds of formula (I), wherein Q is selected from O or S; R 1 is a 5- or 6-membered heteroaryl group consisting of one or more carbon atoms, and one or more nitrogen and/or oxygen atoms, and substituted with a monovalent, optionally substituted cycloalkyl, cycloalkenyl or heterocyclic group, wherein the 5- or 6-membered heteroaryl group of R 1 may optionally be further substituted; R 2 is an α,α′-substituted cyclic group which may optionally be further substituted; R 3 and R 4 are each independently hydrogen, halogen, —OH, —NH 2 , —CN, —R 5 , —OR 5 , —NHR 5 or —N(R 5 ) 2 ; or R 3 and R 4 together with the carbon atom to which they are attached may form a 3- to 7-membered saturated or unsaturated, optionally substituted cyclic group; and R 5 is independently an optionally substituted C 1 -C 4 alkyl group. The present invention further relates to salts, solvates and prodrugs of such compounds, to pharmaceutical compositions comprising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by the inhibition of NLRP3.

PROCESS OF MAKING CFTR MODULATORS

The disclosure provides processes for synthesizing Compound I, and pharmaceutically acceptable salts thereof. This application claims priority from U.S. Provisional Application No. 62/886,660, filed Aug. 14, 2019, which is hereby incorporated by reference in its entirety.Disclosed herein are processes for making a modulator of cystic fibrosis transmembrane conductance regulator (“CFTR”).Cystic fibrosis (CF) is a recessive genetic disease that affects approximately 70,000 children and adults worldwide. Despite progress in the treatment of CF, there is no cure.In patients with CF, mutations in CFTR endogenously expressed in respiratory epithelia lead to reduced apical anion secretion, causing an imbalance in ion and fluid transport. The resulting decrease in anion transport contributes to enhanced mucus accumulation in the lung and accompanying microbial infections that ultimately cause death in CF patients. In addition to respiratory disease, CF patients typically suffer from gastrointestinal problems and pancreatic insufficiency that, if left untreated, result in death. In addition, the majority of males with CF are infertile, and fertility is reduced among females with CF.Sequence analysis of the CFTR gene has revealed a variety of disease-causing mutations (Cutting, G. R. et al. (1990) Nature 346:366-369; Dean, M. et al. (1990) Cell 61:863:870; and Kerem, B-S. et al. (1989) Science 245:1073-1080; Kerem, B-S et al. (1990) Proc. Natl. Acad. Sci. USA 87:8447-8451). To date, greater than 2000 mutations in the CF gene have been identified; currently, the CFTR2 database contains information on 412 of these identified mutations, with sufficient evidence to define 346 mutations as disease-causing. The most prevalent disease-causing mutation is a deletion of phenylalanine at position 508 of the CFTR amino acid sequence and is commonly referred to as the ΔF508 mutation. This mutation occurs in most of the cases of cystic fibrosis and is associated with severe disease.The ...

ENDOPARASITE CONTROL AGENT

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

MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

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

SUBSTITUTED BICYCLIC COMPOUNDS

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): 3. The compound according to claim 2 , having the structure of Formula (I) or a salt thereof claim 2 , wherein:{'sub': 1', '2, 'Ris —OH or —OP(O)(OH);'}{'sub': 2', '2a', '2b, 'Ris Ror R;'}{'sub': '2a', 'claim-text': [{'sub': 2', '3', '3', '2', '5', '3', '2', '2', '3', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '2', '2', '4', '2', '2', '4', '3', '2', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '2', '2', '3, 'is —(CH)CH, —(CH)CH, —CHCH═CHCHCH, —CHCHCH═CHCHCH, —(CH)CH═CHCH, —(CH)CH═C(CH), —(CH)CH═CH, —(CH)CH═CHCH, —CH═C H(CH)CH, —CH═CH(CH)OCH, —CH═CHCHCHCH(CH), —CH═CHCHCHCHOCH, —CHCH═CHCH═CHCH, —CH═CHCHCHCH═CH, —CH═CH(phenyl) wherein said phenyl is substituted with —CH'}, {'sub': 3', '2', '1-3', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '2', '2', '1-2, 'or —OCH; —CH═CH(tetrahydropyranyl), —(CH)(phenyl) wherein said phenyl is substituted with zero to 2 substituents independently selected from F, I, —CH, —OCH, —OCHCH, —OCH(CH), and —CHC(O)N(CH); —(CH)(methyl imidazolyl), —(CH)(methyl pyrazolyl), —(CH)(pyridinyl) wherein said pyridinyl is substituted with zero to 1 substituent selected'}, {'sub': 3', '2', '2', '2', '2', '2', '2-3', '2', '2', '3-4', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '3', '2', '2', '9', '3', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '3', '3', '2', '1-6', '3', '3', '2', '2', '3', '2', '2', '3', '3', '3', '2', '2', '2', '3, 'from —OCH; —(CH)(pyrimidinyl), —(CH)(quinolinyl), —(CH)(tetrahydropyranyl), —CHO(CH)CH, —CHOCHCHCH(CH), —CHOCHCHC(CH), —CHO(CH)CH, —CHOCHCHCHCF, —CHOCHCH═CHCHCH, —CHOCHCH═C(CH), —CHOCHCH═CHCHCHCH, — ...

USE OF PYRAZOLE PROPARGYL ETHERS AS NITRIFICATION INHIBITORS

The present invention relates to novel nitrification inhibitors of formula (I), which are pyrazole propargyl ether compounds. Moreover, the invention relates to the use of compounds of formula (I) as nitrification inhibitors, i.e. for reducing nitrification, as well as agrochemical mixtures and compositions comprising the nitrification inhibitors of formula (I). 2. The compound of claim 1 , whereinn is 0; or{'sup': '2', 'sub': 1', '3, 'n is 1, and Ris C-C-alkyl or phenyl.'}3. The compound of claim 1 , wherein{'sup': 'N', 'Ris H.'}4. The compound of claim 1 , wherein the compound of formula I is present in the form of a pyrazolium salt.5. The compound claim 1 , wherein{'sup': N', 'd', 'a', 'b', 'a', 'b', 'c', 'b', 'b', 'a', 'e', 'f, 'sub': '2', 'Ris C(═O)R, CHRC(═O)OR, CHRC(═O)NRR, CH(C(═O)OR)CH(C(═O)OR) or CHRNR(C═O)R.'}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 , comprising treating a plant growing on soil or soil substituents and/or the locus or soil or 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 , wherein the plant and/or the locus or soil or soil substituents where the plant is growing or is intended to grow is additionally provided with a fertilizer.12. The method of claim 11 , wherein the application of said compound of formula I and of said fertilizer is carried out simultaneously or with a time lag.13. A method for treating a fertilizer or a composition claim 1 , comprising an application of a nitrification inhibitor as defined in .14. The agrochemical mixture of claim 7 , wherein said fertilizer is an solid or liquid ammonium-containing inorganic fertilizer claim 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 ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 129-. (canceled)31: A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.32: The pharmaceutical composition of claim 31 , further comprising an ATreceptor antagonist.33: A method for therapeutically treating hypertension claim 30 , heart failure claim 30 , or renal disease claim 30 , comprising administering to a patient a therapeutically effective amount of the compound of . This application claims the benefit of U.S. Provisional Application No. 61/443,828, filed on Feb. 17, 2011; the entire disclosure of which is incorporated herein by reference.The present invention relates to novel compounds having neprilysin-inhibition activity. The invention also relates to pharmaceutical compositions comprising such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat diseases such as hypertension, heart failure, pulmonary hypertension, and renal disease.Neprilysin (neutral endopeptidase, EC 3.4.24.11) (NEP), is an endothelial membrane bound Zn metallopeptidase found in many organs and tissues, including the brain, kidneys, lungs, gastrointestinal tract, heart, and the peripheral vasculature. NEP degrades and inactivates a number of endogenous peptides, such as enkephalins, circulating bradykinin, angiotensin peptides, and natriuretic peptides, the latter of which have several effects including, for example, vasodilation and natriuresis/diuresis, as well as inhibition of cardiac hypertrophy and ventricular fibrosis. Thus, NEP plays an important role in blood pressure homeostasis and cardiovascular health.NEP inhibitors, such as thiorphan, candoxatril, and candoxatrilat, have been studied as potential therapeutics. Compounds that inhibit both NEP and angiotensin-I converting enzyme (ACE) are also known, and include omapatrilat, gempatrilat, and sampatrilat. Referred to as vasopeptidase inhibitors, this ...

PYRAZOLONE COMPOUND OR SALT THEREOF, PREPARATION METHOD THEREFOR, HERBICIDE COMPOSITION AND USE THEREOF

The present invention belongs to the field of pesticides, particularly relates to a pyrazolone compound or a salt thereof, a preparation method therefor, a herbicidal composition and use thereof. The pyrazolone compound is as described in formula I: 2. The pyrazolone compound or the salt thereof according to claim 1 , which is characterized in that claim 1 ,{'sub': 1', '2, 'RRN represents pyrazolyl substituted by halogen, alkyl or alkoxy, or substituted or unsubstituted 4-8 membered lactam group containing 0-2 heteroatoms selected from O, S and N; or,'}{'sub': 1', '2', '1-4', '1-8', '3-6', '3-6', '1-4, 'one of Rand Rrepresents Cacyl containing O, S or N, which is unsubstituted or substituted by halogen, and the other one represents hydrogen, Calkyl and substituted alkyl containing 1-4 heteroatoms, alkenyl, alkynyl, unsubstituted Ccycloalkyl or Ccycloalkyl substituted by Calkyl;'}{'sub': 3', '1-4', '3-6', '3-6', '1-4, 'Rrepresents hydrogen, Calkyl, alkenyl, alkynyl, unsubstituted Ccycloalkyl or Ccycloalkyl substituted by Calkyl;'}{'sub': '4', 'Rrepresents methyl, ethyl, n-propyl, isopropyl or cyclopropyl;'}{'sub': 'n', 'sup': 6', '7', '6', '7, 'X represents hydrogen, —S(O)R, —Ror substituted or unsubstituted 3-8 membered heteroaryl containing 1-4 heteroatoms, wherein n represents 1, 2 or 3, Rrepresents substituted or unsubstituted alkyl or aryl, and Rrepresents substituted or unsubstituted alkyl, aryl, alkyl acyl or aroyl.'}3. The pyrazolone compound or the salt thereof according to claim 1 , which is characterized in that claim 1 ,{'sub': 1', '2, 'RRN represents pyrazolyl substituted by halogen, alkyl or alkoxy, or substituted or unsubstituted 4-8 membered lactam group containing 0-2 heteroatoms selected from O, S and N; or'}{'sub': 1', '2', '1-4', '1-8', '1-8', '3-6', '3-6', '1-4, 'one of Rand Rrepresents Cacyl containing O, S or N, which is unsubstituted or substituted by halogen, and the other one represents hydrogen, Calkyl, substituted Calkyl containing 1-4 ...

INHIBITORS OF CGAS ACTIVITY AS THERAPEUTIC AGENTS

This disclosure relates to compounds, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating or preventing inappropriate activation of a type I interferon (IFN) response in a subject in need thereof. 2. The compound of claim 1 , wherein L is —N—.3. The compound of claim 1 , wherein L is —CR—.4. The compound of claim 3 , wherein Ris hydrogen claim 3 , C-Calkyl claim 3 , C-Chaloalkyl claim 3 , —NH claim 3 , —NH(C-Calkyl) claim 3 , —N(C-Calkyl) claim 3 , —OH claim 3 , C-Calkoxy claim 3 , C-Chaloalkoxy claim 3 , —C(O)OR claim 3 , —C(O)NRR claim 3 , aryl optionally substituted with one or more R claim 3 , heteroaryl optionally substituted with one or more R claim 3 , heterocycloalkyl optionally substituted with one or more R claim 3 , or C-Ccycloalkyl optionally substituted with one or more R.5. The compound of claim 3 , wherein Ris hydrogen claim 3 , C-Calkyl claim 3 , —C(O)OR claim 3 , aryl optionally substituted with one or more R claim 3 , or heteroaryl optionally substituted with one or more R.6. The compound of claim 3 , wherein Ris hydrogen claim 3 , phenyl claim 3 , or —C(O)OH.7. The compound of claim 3 , wherein Ris hydrogen.8. The compound of any of - claim 3 , wherein Ris heteroaryl optionally substituted with one or more R.9. The compound of any of - claim 3 , wherein Ris imidazol-1-yl optionally substituted with one or more R.10. The compound of any of - claim 3 , wherein Ris unsubstituted imidazol-1-yl.11. The compound of any of - claim 3 , wherein Ris hydrogen claim 3 , halogen claim 3 , C-Calkyl claim 3 , C-Chaloalkyl claim 3 , —NH claim 3 , —NH(C-Calkyl) claim 3 , —N(C-Calkyl) claim 3 , —OH claim 3 , C-Calkoxy claim 3 , C-Chaloalkoxy claim 3 , or phenyl.12. The compound of any of - claim 3 , wherein Ris hydrogen claim 3 , halogen claim 3 , C-Calkyl claim 3 , —NH claim 3 , C-Calkoxy claim 3 , or phenyl.13. The compound of any of - claim 3 , wherein Ris hydrogen claim 3 , methyl claim 3 , or methoxy.14 ...

Fungicidal pyrazoles

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, wherein Q 1 is a phenyl ring, naphthalenyl ring system, a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure; Q 2 is a phenyl ring, a naphthalenyl ring system, a 5- to 6-membered saturated, partially unsaturated or fully unsaturated heterocyclic ring, or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure; X is O, S(O) m , NR 4 , CR 15 R 16 , C(═O) or C(═S); and R 1 , R 1a , R 2 , R 4 , R 15 , R 16 and m are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention. Also disclosed are compounds of Formula 2, including all geometric and stereoisomers, and salts thereof, wherein X is NH; and Q 1 , Q 2 and R 2 are as defined for Formula 1; which are useful as intermediates for preparing compounds of Formula 1.

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 129-. (canceled)30. A compound selected from:(a) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid ethyl ester;(b) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid;(c) (2S,4R)-5-Biphenyl-4-yl-2-hydroxy-2-methyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid(d) (R)-5-Biphenyl-4-yl-2-hydroxy-2-methyl-4-[(2H-[1,2,4]triazole-3-carbonyl)-amino]-pentanoic acid(e) (R)-5-Biphenyl-4-yl-4-[(5-chloro-2H-[1,2,4]triazole-3-carbonyl)-amino]-2-hydroxy-2-methyl-pentanoic acid(f) (R)-5-Biphenyl-4-yl-4-[(7-fluoro-3H-benzotriazole-5-carbonyl)-amino]-2-hydroxy-2-methyl-pentanoic acid(g) (R)-5-Biphenyl-4-yl-4-[(7-chloro-3H-benzotriazole-5-carbonyl)-amino]-2-hydroxy-2-methyl-pentanoic acid(h) (2S,4R)-5-Biphenyl-4-yl-2-hydroxy-2-methyl-4-[(1H-[1,2,3]triazolo[4,5-b]pyridine-6-carbonyl)-amino]-pentanoic acid(i) (R)-5-Biphenyl-4-yl-2-hydroxy-4-[(3-hydroxy-isoxazole-5-carbonyl)-amino]-2-methyl-pentanoic acid ethyl ester(j) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-[(2-hydroxy-pyrimidine-5-carbonyl)-amino]-2-methyl-pentanoic acid; and(k) 5-((1R,3R)-1-Biphenyl-4-ylmethyl-3-carboxy-3-hydroxy-butylcarbamoyl)-1H-pyrazole-3-carboxylic acid;or a pharmaceutically acceptable salt thereof.31. (R)-5-Biphenyl-4-yl-2-hydroxy-4-[(3-hydroxy-isoxazole-5-carbonyl)-amino]-2-methyl-pentanoic acid or a pharmaceutically acceptable salt thereof.32. (2S ,4R)-5-Biphenyl-4-yl-2-hydroxy-4-[(2-hydroxy-pyrimidine-5-carbonyl)-amino]-2-methyl-pentanoic acid or a pharmaceutically acceptable salt thereof.33. 5-((1R ,3S)-1-Biphenyl-4-ylmethyl-3-carboxy-3-hydroxy-butylcarbamoyl)-2H-pyrazole-3-carboxylic acid or a pharmaceutically acceptable salt thereof.34. (R)-5-Biphenyl-4-yl-2-hydroxy-4-[(5-hydroxy-2H-pyrazole-3-carbonyl)-amino]-2-methyl-pentanoic acid or a pharmaceutically acceptable salt thereof.35. A pharmaceutical composition comprising the ...

SUBSTITUTED BICYCLIC COMPOUNDS

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

PYRAZOLONE COMPOUNDS AND USES THEREOF

The invention disclosed herein is directed to compounds of Formula I [Formula should be entered here] and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, acute or chronic myeloid leukemia, melanoma, and other cancers. The invention also includes 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, acute or chronic myeloid leukemia, melanoma and other cancers. The invention disclosed herein is further directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, acute or chronic myeloid leukemia, melanoma and other cancers through the administration of a therapeutically effective amount of a selective PPARa 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. 2. A compound according to or a pharmaceutically acceptable salt thereof wherein:{'sup': 1', '2, 'Rand Rare each independently methyl, optionally mono-, di- or tri-substituted with halogen or'}{'sup': 1', '2, 'sub': 3-6', '1-6', '3, 'Rand Rare joined together to form —Ccycloalkyl, optionally mono or di-substituted with substituents independently selected from halogen, —Calkyl and —CF.'}3. A compound according to or a pharmaceutically acceptable salt thereof wherein:{'sup': 1', '2, 'Rand Rare each independently methyl, optionally mono-, di- or tri-substituted with halogen.'}5. A compound according to or a pharmaceutically acceptable salt thereof wherein:{'sup': '4', 'claim-text': (a) -phenyl,', '(b) -pyridyl,', {'sub': '2', '(c) —CH-phenyl, and'}, {'sub': '2', '(d) —CH- ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 130-. (canceled)31. A compound selected from:(a) (2S,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxymethyl-4-[(3-methoxyisoxazole-5-carbonyl)amino]-2-methylpentanoic acid;(b) (2S,4R)-5-(3′-chlorobiphenyl-4-yl)-4-[(3-methoxyisoxazole-5-carbonyl)amino]-2-methoxymethyl-2-methylpentanoic acid;(c) (2S,4R)-5-(3′-chlorobiphenyl-4-yl)-2-ethoxymethyl-4-[(3-methoxyisoxazole-5-carbonyl)amino]-2-methylpentanoic acid;(d) (2S,4R)-5-biphenyl-4-yl-4-[(3-hydroxyisoxazole-5-carbonyl)amino]-2-hydroxymethyl-2-methylpentanoic acid;(e) (2S,4R)-5-biphenyl-4-yl-4-[(3-hydroxyisoxazole-5-carbonyl)amino]-2-methoxymethyl-2-methylpentanoic acid;(f) (2S,4R)-5-biphenyl-4-yl-4-[(3-methoxyisoxazole-5-carbonyl)amino]-2-methoxymethyl-2-methylpentanoic acid;(g) (2S,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxymethyl-4-[(3-methoxyisoxazole-5-carbonyl)amino]-2-methylpentanoic acid;(h) (2S,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-4-[(3-ethylisoxazole-5-carbonyl)amino]-2-hydroxymethyl-2-methylpentanoic acid;(i) (2S,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxymethyl-4-[(3-isobutylisoxazole-5-carbonyl)amino]-2-methylpentanoic acid;(j) (2S,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxymethyl-2-methyl-4-[(3-propylisoxazole-5-carbonyl)amino]pentanoic acid;(k) (2S,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-4-[(3-hydroxyisoxazole-5-carbonyl)amino]-2-methoxymethyl-2-methylpentanoic acid;(l) (2S,4R)-5-(3′-chlorobiphenyl-4-yl)-2-(2-hydroxyethoxymethyl)-4-[(3-hydroxyisoxazole-5-carbonyl)amino]-2-methylpentanoic acid;(m)(2S,4R)-5-(3′-chlorobiphenyl-4-yl)-2-ethoxymethyl-4-[(3-hydroxyisoxazole-5-carbonyl)amino]-2-methylpentanoic acid;(n) (2S,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-ethoxymethyl-4-[(3-hydroxyisoxazole-5-carbonyl)amino]-2-methylpentanoic acid;(o) (2S,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-ethoxymethyl-4-[(3-ethylisoxazole-5-carbonyl)amino]-2-methylpentanoic acid;(p) (2S,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-4-[(3- ...

PYRAZOLE COMPOUND

The present invention relates to a novel serotonin reuptake inhibitor which also exhibits 5-HTantagonistic action (antidepressive and anxiolytic effects), in particular, 5-HTinverse agonistic action comprising Compound (1): 2. The compound of or a pharmaceutically acceptable salt thereof wherein{'sup': 1', '2', '3, 'R, Rand Rare independently selected from the group consisting of hydrogen atom and methyl group, and'}{'sup': '4', 'Ris hydrogen atom.'}3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein A is an optionally-substituted Caryl group.4. The compound of or a pharmaceutically acceptable salt thereof wherein X is hydrogen atom.5. The compound of or a pharmaceutically acceptable salt thereof wherein L is oxygen atom.6. The compound of or a pharmaceutically acceptable salt thereof wherein n is 1.7. The compound of or a pharmaceutically acceptable salt thereof wherein{'sup': 1', '3', '4, 'R, Rand Rare hydrogen atom, and'}{'sup': '2', 'Ris methyl group.'}8. The compound of or a pharmaceutically acceptable salt thereof wherein R claim 1 , R claim 1 , Rand Rare hydrogen atom.9. The compound of or a pharmaceutically acceptable salt thereof wherein E is an optionally-substituted Ccycloalkyl group claim 1 , an optionally-substituted 5- to 10-membered saturated heterocyclic group which comprises 1 to 3 oxygen atoms as a constituent atom of the ring claim 1 , or an optionally-substituted phenyl group.10. The compound of or a pharmaceutically acceptable salt thereof wherein E is an optionally-substituted Ccycloalkyl group.11. The compound of or a pharmaceutically acceptable salt thereof wherein r is 1 or 2.12. The compound of or a pharmaceutically acceptable salt thereof wherein Ris an optionally-substituted Calkyl group.13. The compound of wherein the compound of Formula (1) is any one of the following compounds claim 1 , or a pharmaceutically acceptable salt thereof:1-[5-(benzyloxy)-1-(cyclohexylmethyl)-1H-pyrazol-3-yl]-N-methylmethanamine ...

Modulators of Cystic Fibrosis Transmembrane Conductance Regulator

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

Novel halogen-substituted compounds

The invention relates to compounds of the general formula (I), 3. The method according to wherein{'sup': '1', 'sub': 1', '6', '2', '6', '2', '6', '3', '7', '1', '6', '1', '6', '1', '2', '1', '3', '1', '3, 'Ris hydrogen or one of the optionally substituted groups C-C-alkyl, C-C-alkylene, C-C-alkynyl, C-C-cycloalkyl, C-C-alkylcarbonyl, C-C-alkoxycarbonyl, cyano-C-C-alkyl, aryl(C-C)-alkyl, or heteroaryl(C-C)-alkyl;'}{'sub': '1', 'sup': '2', 'Ais CRor nitrogen,'}{'sub': '2', 'sup': '3', 'Ais CRor nitrogen,'}{'sub': '3', 'sup': '4', 'Ais CRor nitrogen and'}{'sub': 4', '1', '4, 'sup': '5', 'Ais CRor nitrogen, wherein at most three of the chemical groups Ato Aare nitrogen at the same time, and wherein'}{'sup': 2', '3', '4', '5, 'sub': 2', '1', '6', '1', '6', '3', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '7', '2', '7, 'R, R, Rand R, independently of one another, are hydrogen, halogen, CN, NO, optionally substituted C-C-alkyl, C-C-haloalkyl, C-C-cycloalkyl, C-C-halocycloalkyl, C-C-alkoxy, C-C-haloalkoxy, C-C-alkylthio, C-C-haloalkylthio, C-C-alkylsulphinyl, C-C-haloalkylsulphinyl, C-C-alkylsulphonyl, C-C-haloalkylsulphonyl, N—C-C-alkylaminocarbonyl, or N—C-C-cycloalkylaminocarbonyl,'}provided:{'sub': 2', '3, 'sup': 3', '4, 'if none of the groups Aand Ais nitrogen, then Rand R, together with the carbon to which they are bonded attached, can form a 5- or 6-membered ring which comprises 0, 1 or 2 nitrogen atoms and/or 0 or 1 oxygen atom and/or 0 or 1 sulphur atom, or'}{'sub': 1', '2, 'sup': 2', '3, 'if none of the groups Aand Ais nitrogen, then Rand R, together with the carbon to which they are bonded, can form a 6-membered ring which comprises 0, 1 or 2 nitrogen atoms;'}{'sub': '2', 'U is a group C(═W), SO or SO;'}W is oxygen or sulphur;{'sub': 2', '2', '2', '2', '2', '2', 'p', '2', 'p', '2, 'sup': 6', '6', '6', '6', '6', '6', '6, 'L is a bivalent chemical group which is —CHNHC(═W)—, —CHNRC(═W)—, —C(═W)NH, —C(═W)NR—, — ...

SYNTHESIS OF ENONE INTERMEDIATE

The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The recent development of a modular synthesis of tetracycline analogs through a chiral enone intermediate has allowed for the efficient synthesis of novel tetracycline analogs never prepared before. The present invention provides a more efficient route for preparing the enone intermediate. 148-. (canceled)50. The method of claim 49 , wherein step of substituting results in a retention of stereochemistry at the carbon atom to which Ris attached.51. The method of claim 49 , wherein the step of substituting comprises:converting the hydroxyl group to a leaving group, wherein the step of converting results in an inversion of stereochemistry; andsubstituting the leaving group with a nucleophile, wherein the step of substituting results in a second inversion of stereochemistry.52. The method of claim 51 , wherein the leaving group is a halide.53. The method of claim 52 , wherein the halide is a bromide.55. The method of claim 54 , wherein the step of substituting results in an inversion of stereochemistry at the carbon atom to which Ris attached.56. The method of claim 54 , wherein P′ is acetyl.57. The method of claim 54 , wherein P′ is mesylate.58. The method of claim 54 , wherein P′ is tosylate.59. The method of claim 54 , wherein the step of substituting comprises:deprotecting the acetylated hydroxyl group of formula (IIb), wherein P′ is acetyl;converting the unprotected hydroxyl group into a better leaving group with retention of stereochemistry; andsubstituting the leaving group with a nucleophile.60. The method of claim 59 , wherein the better leaving group is —OMs claim 59 , wherein Ms is mesylate.61102-. (canceled)103. The method of claim 49 , wherein Rand Rare both ...

SUBSTITUTED PYRAZOLES AS HERBICIDES

Disclosed is a method for controlling the growth of undesired vegetation comprising contacting the vegetation or its environment with a herbicidally effective amount of a compound of Formula 1, including all stereoisomers, N-oxides, and salts thereof, 3. The method of wherein{'sup': A', 'B, 'A is C(═O)N(R)(R); or A is A-1;'}{'sup': 1', '2', '2', '3', '4', '5', '2, 'Yis N or CR; and each Y, Y, Yand Yis independently CR;'}{'sup': 'A', 'sub': 1', '6', '1', '4', '1', '4', '3', '6', '4', '8', '1', '4', '1', '4', '1', '4', '1', '3', '1', '4, 'Ris C-Calkyl or C-Calkoxy, each optionally substituted with halogen or C-Calkoxy; or C-Ccycloalkyl or C-Ccycloalkylalkyl, each optionally substituted with halogen, C-Calkyl or C-Calkoxy; or phenyl optionally substituted with halogen, C-Calkyl, C-Chaloalkyl or C-Calkoxy;'}{'sup': 'B', 'sub': 1', '4, 'Ris H or C-Calkyl;'}{'sup': '1', 'sub': 1', '4', '1', '4', '1', '4, 'Ris C-Calkoxy, C-Calkyl or C-Chaloalkyl;'}{'sup': 5', '6, 'Q is —C(R)(R)—;'}J is selected from J-2 through J-14;t is 0 or 1;{'sup': '2', 'sub': 1', '4', '1', '4, 'each Ris independently H, halogen, C-Calkyl or C-Chaloalkyl;'}{'sup': '5', 'Ris H or F;'}{'sup': '6', 'Ris H;'}{'sup': '7', 'sub': 1', '4', '1', '4, 'Ris C-Chaloalkyl or C-Chaloalkoxy; and'}{'sup': '8', 'sub': '3', 'each Ris independently F, Cl or CF.'}4. The method of wherein{'sup': A', 'B, 'A is C(═O)N(R)(R);'}{'sup': 'A', 'sub': 1', '6', '1', '4', '3', '6', '1', '4', '1', '3, 'Ris C-Calkyl or C-Calkoxy, each optionally substituted with halogen; or C-Ccycloalkyl optionally substituted with halogen or C-Calkyl; or phenyl optionally substituted with halogen or C-Chaloalkyl;'}{'sup': 'B', 'sub': 3', '2', '3, 'Ris H, CHor CHCH;'}{'sup': '1', 'sub': 1', '4', '1', '4, 'Ris C-Calkoxy or C-Calkyl;'}J is selected from J-2 and J-5;t is 0;{'sup': '2', 'sub': 3', '3, 'each Ris independently H, F, Cl, CHor CF;'}{'sup': '5', 'Ris H; and'}{'sup': '7', 'sub': 3', '3', '2, 'Ris CF, OCFor OCHF.'}5. The method of wherein{'sup': ...

AROMATIC COMPOUND AND USES THEREOF

A pest control agent comprising an aromatic compound represented by formula (1) wherein Rrepresents a halogen atom, etc.; Rrepresents a hydrogen atom, etc.; Rrepresents a C1-C3 alkyl group optionally having one or more halogen atoms, etc.; Zrepresents a halogen atom, etc.; Zrepresents a C1-C3 alkyl group optionally having one or more halogen atoms, etc.; and Q represents the following group Q1, Q2, or Q3 has excellent control activity. 2. The aromatic compound according to claim 1 , wherein Ris a methyl group claim 1 , Ris a hydrogen atom claim 1 , Ris a hydroxyl group claim 1 , and Xis an oxygen atom.4. A pest control agent comprising the aromatic compound according to .5. A method for controlling pests claim 1 , which comprises treating plants or soil with an effective amount of the aromatic compound according to .6. Use of the aromatic compound according to for controlling pests. The present invention relates to an aromatic compound and uses thereof.Heretofore, various chemicals have been developed so as to control pests and provided in practice use, but in some cases, these chemicals may not exert enough activity.Meanwhile, there have been known, as compounds having an aromatic group, compounds represented by the following formula (X):The present invention provides a compound having excellent control activity against pests.The present inventors have intensively studied so as to find compounds having excellent control activity against pests, and found that an aromatic compound represented by formula (1) shown below has excellent control activity against pests.The present invention is as follows.[1] An aromatic compound represented by formula (1):wherein Rrepresents a halogen atom or a C1-C4 alkyl group optionally having one or more halogen atoms; Rrepresents a hydrogen atom or a C1-C4 alkyl group optionally having one or more halogen atoms; Rrepresents a C1-C3 alkyl group optionally having one or more halogen atoms, a hydrogen atom, a halogen atom, a C1-C3 alkoxy ...

PYRAZOLE COMPOUNDS OR SALTS THEREOF, PREPARATION METHODS THEREFOR, HERBICIDAL COMPOSITIONS AND USE THEREOF

The present invention relates to the technical field of pesticides, particularly relates to a pyrazole compound or a salt thereof, a preparation method therefor, a herbicidal composition and use thereof. A pyrazole compound of formula (I) or a salt thereof: 3. The pyrazole compound or the salt thereof according to claim 2 , which is characterized in that claim 2 ,{'sub': '1', 'Rrepresents hydrogen, methyl, ethyl or cyclopropyl;'}{'sub': '2', 'Rrepresents methyl, ethyl or isopropyl;'}{'sub': 3', '3', '3, 'X represents O, N or S, X and R′ may form a ring or a linear chain, wherein, when X is O or S, R′ represents C1-C6 alkyl, C3-C6 alkoxyl alkyl, C2-C4 halogenated alkyl, C3-C5 alkenyl or C3-C5 alkynyl; when X is N, X and R′ form a pyrazole ring or substituted pyrazole ring, C3-C5 lactam ring or substituted lactam ring.'}{'sub': '4', 'Rrepresents methyl or chlorine;'}{'sub': '5', 'R′ represents methyl, ethyl or isopropyl;'}{'sub': 5', '5, 'R″ represents hydrogen, methyl, ethyl, isopropyl, methoxyl, ethoxyl, difluoromethyl, chloro or bromo; n is 0, 1, or 2, wherein, when n is 2, the two R″ may be the same or different.'}4. The pyrazole compound or the salt thereof according to claim 3 , which is characterized in that claim 3 , X represents O or N claim 3 , X and R′ may form a ring or a linear chain claim 3 , wherein claim 3 , when X is O claim 3 , R′ represents methyl claim 3 , ethyl claim 3 , n-butyl claim 3 , methoxyl ethyl claim 3 , ethoxyl ethyl claim 3 , methoxyl isopropyl claim 3 , methoxyl n-propyl claim 3 , 2 claim 3 ,2-difluoroethyl claim 3 , 2 claim 3 ,2 claim 3 ,2-trifluoroethyl claim 3 , 1 claim 3 ,1 claim 3 ,2 claim 3 ,2-tetrafluoropropyl claim 3 , propargyl claim 3 , 2-butenyl or tetrahydrofurfuryl; when X is N claim 3 , X and R′ form a pyrazole ring claim 3 , 3-methyl pyrazole ring claim 3 , 4-methyl pyrazole ring claim 3 , 3 claim 3 ,5-dimethyl pyrazole ring claim 3 , 4-chloropyrazole ring or pyrrolidone ring.7. The method according to which is ...

Pyrazole indanyl carboxamides

The present invention relates to novel 1-methyl-pyrazole(thio)indanyl carboxamides, to processes for preparing these compounds, to compositions comprising these compounds, and to the use thereof as biologically active compounds, especially for control of harmful microorganisms in crop protection and in the protection of materials.

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.

Process and intermediates for the preparation of pyroxasulfone

The invention provides a process which comprises the step of thiomethylating a pyrazole, to create R2—C(O)—S—CH2— functionality at position 4 of the pyrazole ring. The process is useful in preparing Pyroxasulfone. The invention also provides intermediates. Formula (III);

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, ...

MULTI-TIERED HIGH THROUGH-PUT SCREEN FOR COMPOUNDS EFFECTIVE AGAINST BACTERIAL BIOFILM AND COMPOUNDS EFFECTIVE FOR INHIBITING AND ERADICATING BACTERIAL BIOFILM

A high through-put screening method for identifying agents effective for inhibiting biofilm formation and/or killing established biofilm are disclosed. The method includes three tiers, and each tier includes three specific biological process assays. The tier levels are a primary screen, a confirmation screen, and a dose-response screen, and the biological process assays include assays for total bacterial growth, bacterial metabolic activity, and biofilm formation. The series of assays may be run once or more than once at each tier. A library of compounds is subject to tier A and only compounds meeting a primary parameter advance to tier B, and only tier B compounds meeting a confirmation parameter advance to tier C, and only tier C compounds meeting a dose-response parameter are identified as putative agents effective for inhibiting and/or eradicating a biofilm, further wherein the assays are conducted for each compound subject to the respective tier. The method is effective and validated for identifying agents which inhibit and/or kill , and biofilms. Agents identified according to the high through-put screen and validated in follow-up experiments as effective for inhibiting and/or killing bacterial biofilms are also disclosed. 1S. epidermidis, P. aeruginosaA. baumannii. A compound effective for inhibiting bacterial biofilm formation and/or killing established bacterial biofilm , wherein the bacteria is one or more of , and , and the compound is selected from the compounds set forth in Table 1.2A. baumannii. The compound according to effective for killing established biofilm claim 1 , wherein the compound is selected from 1 claim 1 , 2 claim 1 , 12 claim 1 , 17 claim 1 , 18 claim 1 , 31 claim 1 , and 34.3A. baumannii. The compound according to effective for inhibiting formation of an biofilm claim 1 , wherein the compound is selected from 1 claim 1 , 2 claim 1 , 12 claim 1 , 17 and 18.4P. aeruginosa. The compound according to effective for inhibiting formation of a ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula I: 122-. (canceled)2427-. (canceled) This application claims the benefit of U.S. Provisional Application No. 61/933,406 filed on Jan. 30, 2014 and U.S. Provisional Application No. 62/016,742 filed on Jun. 25, 2014; the entire disclosures of which are incorporated herein by reference.Field of the InventionThe present invention relates to novel compounds having neprilysin-inhibition activity. 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.State of the ArtNeprilysin (neutral endopeptidase, EC 3.4.24.11) (NEP), is an endothelial membrane bound Znmetallopeptidase found in many organs and tissues, including the brain, kidneys, lungs, gastrointestinal tract, heart, and the peripheral vasculature. NEP degrades and inactivates a number of endogenous peptides, such as enkephalins, circulating bradykinin, angiotensin peptides, and natriuretic peptides, the latter of which have several effects including, for example, vasodilation and natriuresis/diuresis, as well as inhibition of cardiac hypertrophy and ventricular fibrosis. Thus, NEP plays an important role in blood pressure homeostasis and cardiovascular health.NEP inhibitors, such as thiorphan, candoxatril, and candoxatrilat, have been studied as potential therapeutics. Compounds that inhibit both NEP and angiotensin-I converting enzyme (ACE) are also known, and include omapatrilat, gempatrilat, and sampatrilat. Referred to as vasopeptidase inhibitors, this latter class of compounds is described in Robl et al. (1999) 9(12): 1665-1677.In spite of these compounds however, there remains a need for NEP inhibitors that have improved potency, different metabolic and cleavage properties, and/or having improved oral absorption. This ...

COMPOUNDS

A compound for use in the treatment of a disease ameliorated by the inhibition of Notum of formula (I): (I) 2. A compound according to claim 1 , wherein Ar is Cheteroaryl claim 1 , with an optional substituent.5. A compound according to claim 2 , wherein there are three heteroatoms in the ring.6. A compound according to claim 1 , wherein the substituent is selected from OH claim 1 , OMe claim 1 , OEt and NHCN.7. A compound according to claim 6 , wherein the substituent is OH.8. A compound according to claim 1 , wherein the substituent is CHOH.9. A compound according to claim 1 , wherein there is no substituent on Ar.1020-. (canceled)21. A compound according to claim 1 , wherein Ris Cl claim 1 , Ris CFand Ris Cl.2224-. (canceled)25. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.26. (canceled)28. A compound according to claim 1 , wherein the compound is selected from:4-[2,4-dichloro-3-(trifluoromethyl)phenyl]-1H-triazole (306);2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-(methoxy-d3)-1,3,4-oxadiazole (241);2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-ethoxy-1,3,4-oxadiazole (242);4,5-dideuterio-1-[2,4-dichloro-3-(trifluoromethyl)phenyl]triazole (308);5-[2,4-dichloro-3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-ol (261);2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-methoxy-1,3,4-oxadiazole (243);1-[2,4-dichloro-3-(trifluoromethyl)phenyl]triazole (295); andN-(5-(2,4-dichloro-3-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)cyanamide, ammonia salt (246).29. 1-[2 claim 1 ,4-dichloro-3-(trifluoromethyl)phenyl]triazole (295).30. A method of treatment of a disease or disorder ameliorated by the inhibition of Notum claim 1 , comprising administering to a patient in need of treatment claim 1 , a compound as defined in .31. A method according to claim 30 , wherein the disease or disorder is a neurodegenerative disorder or a central nervous system disorder.32. A method according to claim 30 , wherein the disease or ...

Geranyl Geranyl Acetone Analogs and Uses Thereof

The invention relates to novel therapeutic compounds, more in particular to biologically active analogs and uses thereof as medicament, for instance for the treatment of atrial fibrillation. Provided is a compound of the general formula (formula I) wherein Ris H or a saturated or unsaturated aliphatic moiety comprising 1 to 8 C-atoms; and X is selected from the group consisting of moieties X, X, X, X, Xand X. Exemplary uses include the prevention or therapeutic treatment of a HSF1-mediated disease. 141-. (canceled)43. The compound or salt according to claim 42 , wherein Ris H.44. The compound or salt according to claim 42 , wherein X is X.45. The compound or salt according to claim 44 , wherein Ris H or C-Calkyl.46. The compound or salt according to claim 44 , wherein at least one of Rand Ris C-Calkyl claim 44 , optionally substituted with one or more of halogen claim 44 , oxo claim 44 , hydroxyl claim 44 , — CN claim 44 , alkoxy claim 44 , amino claim 44 , amido claim 44 , phenyl claim 44 , benzyl claim 44 , hetero-aryl claim 44 , cyclo-alkyl claim 44 , heterocycloalkyl claim 44 , —C(═O)O—R3a claim 44 , wherein R3a is H claim 44 , C-Calkyl or CH-aryl.47. The compound or salt according to claim 44 , wherein the compound is selected from compounds 28 claim 44 , 22 claim 44 , 76 claim 44 , 69 claim 44 , 70 claim 44 , 24 claim 44 , 23 claim 44 , 84 claim 44 , 78 claim 44 , 89 claim 44 , 82 claim 44 , and 125 shown in .48. The compound or salt according to claim 42 , wherein X is X.49. The compound or salt according to claim 48 , wherein Rand/or Ris H or wherein Rand/or Ris a substituted or unsubstituted C-Cstraight chain alkyl.50. The compound or salt according to claim 48 , wherein the compound is selected from compounds 62 claim 48 , 64 claim 48 , and 65 shown in .51. The compound or salt according to claim 42 , wherein X is X.52. The compound or salt of claim 51 , wherein the compound is compound 111 shown in .53. The compound or salt according to claim 42 , wherein ...

Cyclopropaneamine compound

The present invention provides a compound having a lysine-specific demethylase 1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for cancer, and central nervous system diseases, and the like. The present invention relates to a compound represented by the formula wherein A is a hydrocarbon group or heterocyclic group optionally having substituent(s); R is H, a hydrocarbon group or heterocyclic group optionally having substituent(s); A and R are optionally bonded to each other to form a ring optionally having substituent(s); Q 1 , Q 2 , Q 3 and Q 4 are each a hydrogen atom or a substituent; Q 1 and Q 2 , and Q 3 and Q 4 , are each optionally bonded to each other to form a ring optionally having substituent(s); X is H, an acyclic hydrocarbon group or saturated cyclic group optionally having substituent(s); Y 1 , Y 2 and Y 3 are each H, a hydrocarbon group or heterocyclic group optionally having substituent(s); X and Y 1 , and Y 1 and Y 2 , are each optionally bonded to each other to form a ring optionally having substituent(s); and Z 1 , Z 2 and Z 3 are each H or a substituent, or a salt thereof.

SULFONYLCYCLOALKYL CARBOXAMIDE COMPOUNDS

The invention is concerned with the compounds of formula I: 2. The compound of wherein n is 2.3. The compound of wherein n is 3.4. The compound of wherein Ris aryl substituted with a substituent selected from Br claim 1 , Cl claim 1 , F claim 1 , —CHF claim 1 , —CF claim 1 , CHCland —CClat any of the ortho claim 1 , meta or para positions.6. The compound of wherein m is 0.7. The compound of wherein m is 1 or 2 and wherein each Ris independently selected from —CH claim 1 , —CHCH claim 1 , —CH-cyclopropane claim 1 , —CF claim 1 , —CN and F.8. The compound of wherein Ris —NH—C(O)—.9. The compound of wherein Ris —C(O)—NH—.23. A pharmaceutical composition claim 1 , comprising a compound as described in any one of or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent or excipient.23. A method for treating a disease or condition mediated by TRPA1 activity in a mammal claim 1 , comprising administering a compound of or a pharmaceutically acceptable salt thereof to the mammal.24. The method of wherein the disease or condition is pain claim 23 , arthritis claim 23 , itch claim 23 , cough claim 23 , asthma claim 23 , inflammatory bowel disease claim 23 , or an inner ear disorder. This application is a Continuation of PCT/EP2017/068171 filed Jul. 18, 2017, which claims the benefit of priority to International Patent Application No. PCT/CN2016/090637 filed 20 Jul. 2016, the contents of which application is hereby incorporated by reference in their entirety.The invention relates to sufonyl cyclobutyl and cyclopentyl carboxamine compounds, their manufacture, pharmaceutical compositions containing them and their use as Transient Receptor Potential (TRP) channel antagonists.TRP channels are a class of ion channels found on the plasma membrane of a variety of human (and other animal) cell types. There are at least 28 known human TRP channels which are broken into a number of families or groups based upon sequence homology ...

Process for the Manufacture of Pyrazoles or Pyrimidones

In one aspect the invention relates to the use of an amine compound in a process for the manufacture of a fluorinated or non-fluorinated 5- or 6-membered heterocyclic compound containing two nitrogen atoms in the ring system of the said compound, preferably of pyrazoles or pyrimidones. The invention also relates to a process for the manufacture of pyrazoles or pyrimidones, which may be fluorinated or may not be fluorinated (non-fluorinated). Especially, the invention relates to process for the manufacture of fluorinatedpyrazoles or pyrimidones, and in particular the invention relates to process for the manufacture of such fluorinatedpyrazoles or pyrimidones, which each are very important building blocks for pharmaceutical and agro-applications. For example, the fungicides are Bixafen, Fluxapyroxad, Fluindapyr, Sedaxane, Isopyrazam and Benzovindifupyr strongly depend on such fluorinatedpyrazoles as key building blocks, or for Florasulam and Clorasulam-methyl (Diclosulam), respectively. 1. A use of an amine compound of formula (I) , R4—NH—X , and/or a monohydrate thereof , whereinR4 denotes H or a branched or non-branched C1-C4 alkyl group, and{'sub': '2', 'X denotes a NHgroup or C(═NH)—OR5 group, wherein R5 denotes a branched or non-branched C1-C4 alkyl group,'}in a process for the manufacture of a fluorinated or non-fluorinated 5- or 6-membered heterocyclic compound containing two nitrogen atoms in the ring system of the said compound, comprising a steps of feeding the said amine compound into at least one continuous flow reactor with upper lateral dimensions of up to about 1 cm, preferably with upper lateral dimensions of up to about ≤5 mm, preferably into at least one microreactor, and therein reacting the said amine compound with a carbonyl group containing three ring-carbon-atom precursor compound for the fluorinated or non-fluorinated 5- or 6-membered heterocyclic compound containing two nitrogen atoms in the ring system.2. The use of an amine compound of ...

Heteroarylphenoxy benzamide kappa opioid ligands

The present invention provides compounds of Formula I: and pharmaceutically acceptable salts thereof wherein the variables R 1 , R 2 , R 3 , R 4 , R 9 , X, m and n are as defined herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating kappa opioid (κ-opioid) associated disorders including, e.g., a neurological disorder, or psychiatric disorder such as a neurocognitive disorder, substance abuse disorder, depressive disorder, anxiety disorder, trauma and stressor related disorder and feeding and eating disorder.

Fungicidal pyrazoles and their mixtures

Disclosed is a fungicidal composition comprising (a) at least one compound selected from the compounds of Formula 1, N-oxides, and salts thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in the disclosure; and (b) at least one additional fungicidal compound. Also disclosed is a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1, an N-oxide, or salt thereof (e.g., as a component in the aforesaid composition). Also disclosed is a composition comprising: (a) at least one compound selected from the compounds of Formula 1 described above, N-oxides, and salts thereof; and at least one invertebrate pest control compound or agent.

Acly inhibitors and uses thereof

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

Modulator of the Cystic Fibrosis Transmembrane Conductance Regulator, Pharmaceutical Compositions, Methods of Treatment, and Process for Making the Modulator

Compounds of Formula (I): pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed. Also disclosed are solid state forms of Compound 1 and salts and solvates thereof.

AMINO ACID TRANSPORT INHIBITORS AND THE USES THEREOF

These compounds are glutamine transporter inhibitors, e.g., alanine, serine, cysteine-preferring transporter 2 (ASCT2) inhibitors. Glutamine transporter inhibitors are useful to treat a variety of diseases, disorders, or conditions including cancer. 4. The compound of claim 1 , wherein Ris optionally substituted heteroaryl claim 1 , or a pharmaceutically acceptable salt or solvate thereof.5. The compound of claim 1 , wherein Ris optionally substituted aryl claim 1 , or a pharmaceutically acceptable salt or solvate thereof.7. The compound of claim 6 , wherein R claim 6 , R claim 6 , R claim 6 , R claim 6 , R claim 6 , and Rare each hydrogen claim 6 , or a pharmaceutically acceptable salt or solvate thereof.8. The compound of claim 1 , wherein Q is Q-1 claim 1 , or a pharmaceutically acceptable salt or solvate thereof.10. The compound of claim 1 , wherein Q is Q-2 claim 1 , or a pharmaceutically acceptable salt or solvate thereof.12. The compound of claim 1 , wherein Q is Q-3 claim 1 , or a pharmaceutically acceptable salt or solvate thereof.14. The compound of claim 1 , wherein Q is Q-4 claim 1 , or a pharmaceutically acceptable salt or solvate thereof.16. The compound of claim 1 , wherein Q is Q-5 claim 1 , or a pharmaceutically acceptable salt or solvate thereof.18. The compound of claim 1 , wherein R is hydrogen claim 1 , or a pharmaceutically acceptable salt or solvate thereof.19. The compound of selected from the group consisting of:5-([1,1′-biphenyl]-4-yl)-1H-indole-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)benzofuran-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)benzo[b]thiophene-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)-1H-benzo[d]imidazole-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)benzo[d]oxazole-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)benzo[d]thiazole-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)furo[3,2-b]pyridine-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)thieno[3,2-b]pyridine-2-carboxylic ...

PYRAZOLONE COMPOUNDS AND USES THEREOF

The invention disclosed herein is directed to compounds of Formula I [Formula should be entered here] and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, acute or chronic myeloid leukemia, melanoma, and other cancers. The invention also includes 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, acute or chronic myeloid leukemia, melanoma and other cancers. The invention disclosed herein is further directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, acute or chronic myeloid leukemia, melanoma and other cancers through the administration 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. 2. A compound according to or a pharmaceutically acceptable salt thereof wherein:{'sup': 1', '2, 'Rand Rare each independently methyl, optionally mono-, di- or tri-substituted with halogen or'}{'sup': 1', '2, 'sub': 3-6', '1-6', '3, 'Rand Rare joined together to form —Ccycloalkyl, optionally mono or di-substituted with substituents independently selected from halogen, —Calkyl and —CF.'}3. A compound according to or a pharmaceutically acceptable salt thereof wherein:{'sup': 1', '2, 'Rand Rare each independently methyl, optionally mono-, di- or tri-substituted with halogen.'}5. A compound according to or a pharmaceutically acceptable salt thereof wherein:{'sup': '4', 'claim-text': (a) -phenyl,', '(b) -pyridyl,', {'sub': '2', '(c) —CH-phenyl, and'}, {'sub': '2', '(d) —CH- ...

SUBSTITUTED BENZENE COMPOUNDS

The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes. 6. The compound of any one of - , Z is NRR.7. The compound of any one of - , wherein Ris C-Caryl or 5- or 6-membered heteroaryl , each of which is optionally , independently substituted with one or more -Q-T , wherein Qis a bond or C-Calkyl linker , and Tis H , halo , cyano , —OR , —NRR , —C(O)NRR , —NRC(O)R , —S(O)R , —S(O)NRR , or R , in which each of Rand R , independently is H or R , each of Rand R , independently , is C-Calkyl , or Rand R , together with the N atom to which they are attached , form a 4 to 7-membered heterocycloalkyl ring having 0 or 1 additional heteroatom , and each of R , R , and the 4 to 7-membered heterocycloalkyl ring formed by Rand R , is optionally , independently substituted with one or more -Q-T , wherein Qis a bond or C-Calkyl linker and Tis selected from the group consisting of H , halo , C-Calkyl , 4 to 7-membered heterocycloalkyl , OR , —S(O)R , and —NRR , each of Rand Rindependently being H or C-Calkyl optionally substituted with OH , O—C-Calkyl , or NH—C-Calkyl , or -Q-Tis oxo; or any two neighboring -Q-T , together with the atoms to which they are attached form a 5- or 6-membered ring optionally containing 1-4 heteroatoms selected from N , O and S.8. The compound of claim 7 , wherein Ris phenyl or pyridyl claim 7 , Qis a bond or methyl linker claim 7 , and Tis H claim 7 , halo claim 7 , —OR claim 7 , —NRR claim 7 , or —S(O)NRR.9. The compound of any one of - claim 7 , wherein Ris halo claim 7 , C-Calkyl claim 7 , C-Calkenyl claim 7 , C-Ccycloalkyl claim 7 , C(O)H claim 7 , or —C(O)R claim 7 , in which Ris C-Calkyl or 4 to 12-membered ...

BENZENESULFONAMIDO AND RELATED COMPOUNDS FOR USE AS AGONISTS OF RORy AND THE TREATMENT OF DISEASE

The invention provides benzenesulfonamido and related compounds, pharmaceutical compositions, methods of promoting RORγ activity, increasing the amount of IL-17 in a subject, and treating cancer using such benzenesulfonamido and related compounds. 2. The compound of claim 1 , wherein A is phenylene or 5-6 membered heteroarylene.3. The compound of or claim 1 , wherein Rrepresents independently for each occurrence halogen or Calkyl.5. The compound of any one of - claim 1 , wherein A is phenylene.6. The compound of any one of - claim 1 , wherein A is a 5-6 membered heteroarylene.7. The compound of any one of - claim 1 , wherein n is 1.8. The compound of any one of - claim 1 , wherein n is 1 or 2.9. The compound of any one of - claim 1 , wherein Ris Chaloalkyl.10. The compound of any one of - claim 1 , wherein Ris trifluoromethyl.12. The compound of any one of - claim 1 , wherein Ris Calkyl optionally substituted with 1 claim 1 , 2 claim 1 , or 3 substituents independently selected from the group consisting of —COR claim 1 , halogen claim 1 , hydroxyl claim 1 , and Calkoxy.13. The compound of any one of - claim 1 , wherein Ris Calkyl substituted with —COR.14. The compound of any one of - claim 1 , wherein Ris ethyl or propyl.15. The compound of any one of - claim 1 , wherein X is —O-aralkyl claim 1 , —O-heteroaralkyl claim 1 , —O-phenyl claim 1 , —O-heteroaryl claim 1 , —O-(partially unsaturated bicyclic carbocyclyl) claim 1 , —O—(Calkylene)-(Ccycloalkyl) claim 1 , —N(R)-aralkyl claim 1 , —N(R)-phenyl claim 1 , —N(R)-(partially unsaturated bicyclic carbocyclyl) claim 1 , or —N(R)—(Calkylene)-(Ccycloalkyl) claim 1 , each of which is optionally substituted with 1 claim 1 , 2 claim 1 , or 3 substituents independently selected from the group consisting of halogen claim 1 , Chaloalkyl claim 1 , Calkyl claim 1 , Ccycloalkyl claim 1 , Calkoxy claim 1 , and Chaloalkoxy.16. The compound of any one of - claim 1 , wherein X is —O-aralkyl claim 1 , —O-(partially unsaturated ...

TETRAZOLINONE COMPOUNDS AND THEIR USE AS PESTICIDES

The present invention provides a compound having an excellent efficacy for controlling pests. A tetrazolinone compound of a formula (1) [wherein Q represents a group selected from the following group: Q1, Q2, Q3 or Q4: R, R, Rand Rrepresent independently of each other a halogen atom, an CI-C6 alkyl group, etc.; Rand Rrepresent independently of each other a hydrogen atom, a halogen atom or an C1-C3 alkyl group, etc.; Rrepresents a halogen atom, an C1-C4 alkyl group, etc.; R, Rand Rrepresent independently of each other a hydrogen atom, a halogen atom, etc.; and Rrepresents an C1-C3 alkyl group, etc.] shows an excellent controlling efficacy on pests. 2. The tetrazolinone compound according to wherein Q represents Q1.3. The tetrazolinone compound according to wherein Q represents Q2.4. The tetrazolinone compound according to wherein Q represents Q3.5. The tetrazolinone compound according to wherein Q represents Q4.6. The tetrazolinone compound according to claim 1 ,wherein{'sup': '1', 'Rrepresents an C1-C3 alkyl group, a halogen atom, a C1-C3 haloalkyl group, an C2-C3 alkynyl group, a C2-C3 haloalkynyl group, a C3-C5 cycloalkyl group, a C3-C5 halocycloalkyl group, an C1-C3 alkoxy group or a C1-C3 haloalkoxy group;'}{'sup': 2', '4', '5', '7', '8', '9', '11, 'R, R, R, R, R, Rand Rrepresent a hydrogen atom;'}{'sup': '3', 'Rrepresents a hydrogen atom, a halogen atom, an C1-C3 alkyl group or a C1-C3 haloalkyl group;'}{'sup': '6', 'Rrepresents an C1-C4 alkyl group, a halogen atom, an C1-C4 alkoxy group, a C1-C4 haloalkyl group, an C2-C4 alkenyl group or a C2-C4 haloalkenyl group;'}{'sup': '10', 'Rrepresents a methyl group; and'}X represents an oxygen atom.7. The tetrazolinone compound according to claim 1 ,wherein{'sup': 1', '2, 'Yand Ymay combine each other together with the carbon atom to which they are attached to form a five- or six-membered saturated ring;'}{'sup': 2', '3, 'Yand Ymay combine each other together with the carbon atom to which they are attached to form a ...

PHENOXYMETHYL DERIVATIVES

The invention provides novel compounds having the general formula (I) 5. A compound according to any one of to , wherein Ris selected from the group consisting of{'sub': 1', '6, 'i) C-C-alkyl,'}{'sub': 1', '6, 'ii) cyano-C-C-alkyl,'}{'sub': 3', '8, 'iii) C-C-cycloalkyl,'}{'sub': G', 'G1, 'iv) aryl substituted with Rand R,'}{'sub': G', 'G1', 'G', 'G1, 'v) heterocycloalkyl substituted with Rand R, and vi) heteroaryl substituted with Rand R.'}6. A compound according to any one of to , wherein Ris selected from the group consisting of{'sub': 1', '6, 'i) C-C-alkyl,'}{'sub': 1', '6, 'ii) cyano-C-C-alkyl,'}{'sub': 3', '8, 'iii) C-C-cycloalkyl,'}{'sub': G', 'G1, 'iv) phenyl substituted with Rand R,'}{'sub': G', 'G1, 'v) tetrahydropyranyl substituted with Rand R, and'}{'sub': G', 'G1, 'vi) heteroaryl substituted with Rand R, wherein heteroaryl is selected from benzoxazolonyl, imidazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridinyl and pyrimidinyl.'}7. A compound according to any one of to , wherein Ris selected from the group consisting of{'sub': 1', '6, 'i) C-C-alkyl,'}{'sub': 3', '8, 'ii) C-C-cycloalkyl,'}{'sub': G', 'G1, 'iii) phenyl substituted with Rand R, and'}{'sub': G', 'G1, 'iv) heteroaryl substituted with Rand R, wherein heteroaryl is selected from isoxazolyl and pyridinyl.'}8. A compound according to any one of to , wherein Ris selected from the group consisting of{'sub': 1', '6, 'i) C-C-alkyl, and'}{'sub': G', 'G1, 'ii) phenyl substituted with Rand R.'}9. A compound according to any one of to , wherein Ris C-C-alkyl.10. A compound according to any one of to , wherein Ris phenyl substituted with Rand R11. A compound according to any one of to , wherein Ris selected from the group consisting ofi) H,{'sub': 1', '6, 'ii) C-C-alkoxy,'}{'sub': 1', '6', '1', '6', '1', '6, 'iii) C-C-alkoxy-C-C-alkylcarbonylamino-C-C-alkyl,'}{'sub': 1', '6', '1', '6', '1', '6', '1', '6, 'iv) C-C-alkoxy-C-C-alkylcarbonyl(C-C-alkyl)amino-C-C-alkyl,'}{'sub': 1', '6, 'v) C-C- ...

CARBON MONOXIDE PRODRUGS FOR THE TREATMENT OF MEDICAL DISORDERS

The present invention provides new compounds and compositions thereof that release carbon monoxide for the treatment of medical disorders that are responsive to carbon monoxide, for example, inflammatory, pain, and dermatological disorders. 8. A method for the treatment of a medical disorder that can be treated with carbon monoxide comprising administering an effective amount of a compound of or a pharmaceutically acceptable salt thereof claim 1 , optionally in a pharmaceutically acceptable carrier claim 1 , to a subject in need thereof.9. The method of claim 8 , wherein the medical disorder is an inflammatory disorder or a pain disorder.10. The method of claim 8 , wherein the medical disorder is selected from neuropathic pain claim 8 , inflammatory pain claim 8 , postoperative pain claim 8 , osteoarthritis claim 8 , pain associated with metastatic cancer claim 8 , trigeminal neuralgia claim 8 , acute herpetic neuralgia claim 8 , post-herpetic neuralgia claim 8 , diabetic neuropathy claim 8 , causalgia claim 8 , brachial plexus avulsion claim 8 , occipital neuralgia claim 8 , reflex sympathetic dystrophy claim 8 , fibromyalgia claim 8 , gout claim 8 , phantom limb pain claim 8 , acne vulgaris claim 8 , atherosclerosis claim 8 , ischemia reprufusion injury claim 8 , acute kidney injury claim 8 , heavy metal poisoning claim 8 , pancreatitis claim 8 , and chemotherapy-induced acute kidney injury claim 8 , and chemotherapy-induced cardiotoxicity.19. The method of claim 11 , wherein the medical disorder is an inflammatory disorder or a pain disorder.20. The method of claim 11 , wherein the medical disorder is selected from neuropathic pain claim 11 , inflammatory pain claim 11 , postoperative pain claim 11 , osteoarthritis claim 11 , pain associated with metastatic cancer claim 11 , trigeminal neuralgia claim 11 , acute herpetic neuralgia claim 11 , post-herpetic neuralgia claim 11 , diabetic neuropathy claim 11 , causalgia claim 11 , brachial plexus avulsion claim 11 , ...

PYRAZOLE COMPOUND

The present invention relates to a novel serotonin reuptake inhibitor which also exhibits 5-HTantagonistic action (antidepressive and anxiolytic effects), in particular, 5-HTinverse agonistic action comprising Compound (1): 117-. (canceled)19. The method of claim 18 , wherein R claim 18 , Rand Rare independently selected from the group consisting of a hydrogen atom and a methyl group claim 18 , and Ris a hydrogen atom.20. The method of claim 18 , wherein A is an optionally-substituted Caryl group.21. The method of claim 18 , wherein Xis a hydrogen atom.22. The method of claim 18 , wherein L is an oxygen atom.23. The method of claim 18 , wherein n is 1.24. The method of claim 18 , wherein R claim 18 , Rand Rare hydrogen atoms claim 18 , and Ris a methyl group.25. The method of claim 18 , wherein R claim 18 , R claim 18 , Rand Rare hydrogen atoms.26. The method of claim 18 , wherein E is an optionally-substituted Ccycloalkyl group claim 18 , an optionally-substituted 5- to 10-membered saturated heterocyclic group containing 1 to 3 oxygen atoms as a constituent atom of the ring claim 18 , or an optionally-substituted phenyl group.27. The method of claim 18 , wherein E is an optionally-substituted Ccycloalkyl group.28. The method of claim 18 , wherein r is 1 or 2.29. The method of claim 18 , wherein Ris an optionally-substituted Calkyl group.30. The method of claim 18 , wherein the compound of Formula (1) or a pharmaceutically acceptable salt thereof is at least one selected from the group consisting of:1-[5-(benzyloxy)-1-(cyclohexylmethyl)-1H-pyrazol-3-yl]-N-methylmethanamine;1-{1-(cyclohexylmethyl)-5-[(2-fluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine;1-{1-(cyclohexylmethyl)-5-[(3-fluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine;1-{1-(cyclohexylmethyl)-5-[(4-fluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine;1-{5-[(2-chlorobenzyl)oxy]-1-(cyclohexylmethyl)-1H-pyrazol-3-yl}-N-methylmethanamine;1-{5-[(3-chlorobenzyl)oxy]-1-(cyclohexylmethyl)-1H-pyrazol-3 ...

SUBSTITUTED BENZENE AND 6,5-FUSED BICYCLIC HETEROARYL COMPOUNDS

The present invention relates to substituted benzene compounds and bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes. 3. The compound of or , wherein Z is OR , in which Ris C-Caryl or 5 to 6-membered heteroaryl optionally substituted with one or more -Q-T.4. The compound of claim 3 , wherein Ris phenyl optionally substituted with one or more -Q-T.5. The compound of or claim 3 , wherein Z is CHRR claim 3 , in which Ris —OR claim 3 , and Ris C-Caryl or 5 to 6-membered heteroaryl optionally substituted with one or more -Q-T claim 3 , and Ris C-Calkyl.6. The compound of claim 5 , wherein Ris phenyl optionally substituted with one or more -Q-T.8. The compound of claim 7 , wherein Ris H.10. The claim 9 , wherein Ris C-Caryl or 5- or 6-membered heteroaryl claim 9 , each of which is optionally claim 9 , independently substituted with one or more -Q-T claim 9 , wherein Qis a bond of C-Calkyl linker claim 9 , and Tis H claim 9 , halo claim 9 , cyano claim 9 , —OR claim 9 , —NRR claim 9 , —C(O)NRR claim 9 , —NRC(O)R claim 9 , —S(O)R claim 9 , S(O)NRR claim 9 , or R claim 9 , in which each of Rand R claim 9 , independently is H or R claim 9 , each of Rand R claim 9 , independently claim 9 , is C-Calkyl claim 9 , or Rand Rtogether with the N atom to which they are attached claim 9 , form a 4 to 7-membered heterocycloalkyl ring having 0 to 1 additional heteroatom claim 9 , and each of R claim 9 , R claim 9 , and the 4 to 7-membered heterocycloalkyl ring formed by Rand R claim 9 , is optionally claim 9 , independently substituted with one or more -Q-T claim 9 , wherein Qis a bond or C-Calkyl linker and Tis selected from the group consisting of H claim 9 , halo claim 9 , C- ...

Fungicidal pyrazoles

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, wherein Q 1 is a phenyl ring, naphthalenyl ring system, a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure; Q 2 is a phenyl ring, a naphthalenyl ring system, a 5- to 6-membered saturated, partially unsaturated or fully unsaturated heterocyclic ring, or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure; X is O, S(O) m , NR 4 , CR 15 R 16 , C(═O) or C(═S); and R 1 , R 1a , R 2 , R 4 , R 15 , R 16 and m are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention. Also disclosed are compounds of Formula 2, including all geometric and stereoisomers, and salts thereof, wherein X is NH; and Q 1 , Q 2 and R 2 are as defined for Formula 1; which are useful as intermediates for preparing compounds of Formula 1.

FUNGICIDAL PYRAZOLES

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, 2. A compound of wherein:{'sup': 1', '3', '3', '3, 'Qis phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R; provided that when an Rsubstituent is located at a meta position, then said Rsubstituent is selected from F, Cl, Br and cyano;'}{'sup': 2', '3', '3', '3, 'Qis phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1, 2 or 3 substituents independently selected from R, provided that when an Rsubstituent is located at a meta position, then said Rsubstituent is selected from F, Cl, Br and cyano;'}{'sup': 4', '15', '16, 'X is O, NR, C(═O) or CRR;'}{'sup': 1', '5', '6', '7, 'sub': 1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '5, 'Ris H, halogen, C-Calkyl, C-Chaloalkyl, COR, C(O)NRR, cyano, C-Calkoxy, C-Chaloalkoxy or C-Calkoxyalkyl;'}{'sup': '1a', 'Ris H;'}{'sup': '2', 'sub': 3', '2', '3, 'Ris CH, CHCH, Cl or Br;'}{'sup': '3', 'sub': 1', '4', '1', '4', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '3', '4', '2, 'each Ris independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C-Calkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy C-Calkylthio, C-Chaloalkylthio, C-Calkylsulfinyl, C-Chaloalkylsulfinyl, C-Calkylsulfonyl, C-Chaloalkylsulfonyl, C-Ccycloalkyl, C(═S)NHand —U—V-T;'}{'sup': 4', '10', '12, 'sub': 3', '7', '1', '6', '1', '6, 'Ris H, formyl, C-Ccycloalkyl or —SR; or C-Calkyl or C-Chaloalkyl, each optionally substituted with up to 2 R;'}{'sup': '5', 'sub': 1', '6, 'Ris C-Calkyl;'}{'sup': '6', 'sub': 1', '6, 'Ris H or C-Calkyl;'}{'sup': '7', 'sub': 1', '6', '1', '6', '4', '8, 'Ris H, C-Calkyl, C-Chaloalkyl or C-Calkylcycloalkyl; or'}{'sup': 6', '7', '13, 'Rand Rare taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ...

METHOD FOR PREPARATION OF 1-METHYL-3-(TRIFLUOROMETHYL)-1H-PYRAZOL-5-OL

The invention discloses a method for the preparation of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol with high selectivity with respect to the content of the isomer 1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-ol. 2. The method according to claim 1 , wherein the charging of methyl hydrazine to compound of formula (3) is done in a time TIME1ADD claim 1 , and TIME1ADD is from 10 minutes to 6 hours.3. The method according to claim 1 , wherein REAC1 is done in aqueous medium and without the addition of a solvent other than water.4. The method according to claim 1 , wherein in REAC1 compound of formula (3) and methyl hydrazine are brought into contact in the presence of an acid ACID1 and are reacted in the presence of ACID1;{'sub': 3', '4, 'wherein ACID1 is selected from the group consisting of sulfuric acid, acetic acid, trifluoro acetic acid, HPO, methane sulfonic acid, formic acid, polymeric sulfonic acid resin, and mixtures thereof.'}5. The method according to claim 4 , wherein the molar amount of ACID1 is from 0.001 to 0.25 times of the molar amount of compound of formula (3).6. The method according to claim 4 , wherein the molar amount of ACID1 is from 0.005 to 0.25 times of the molar amount of compound of formula (3).7. The method according to claim 1 , wherein methyl hydrazine is used as an aqueous solution.8. The method according to claim 1 , wherein TEMP1CONT and TEMP1REAC are from 60 to 140° C.9. The method according to claim 1 , wherein ST1 comprises a distillation DIST1 that is done during or after REAC1 claim 1 , wherein ethanol is distilled off.10. The method according to claim 1 , wherein ST1 comprises the addition of a solvent SOLV1 claim 1 , and SOLV1 is added after REAC1;wherein SOLV1 is selected from the group consisting of ethyl acetate, butyl acetate, valero nitrile, chloro benzene, dichloro benzene, 1,2-dichloro ethane, and mixtures thereof. The invention discloses a method for the preparation of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol with high ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 130-. (canceled)3029: The method according to claim , wherein the hypertension is resistant hypertension. This application claims the benefit of U.S. Provisional Application No. 61/680,804, filed on Aug. 8, 2012 and U.S. Provisional Application No. 61/774,163, filed on Mar. 7, 2013; the entire disclosures of which are incorporated herein by reference.The present invention relates to novel compounds having neprilysin-inhibition activity or which are metabolized in vivo to compounds having such activity. 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.Commonly-assigned U.S. Patent Publication No. 2012/0213806, filed on Feb. 16, 2012 to Fleury 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 formula I:where:(i) X isandor Ris —Calkyl or —C(O)—Calkyl, and Ris H; ororor(ii) X isandoror(iii) X isandoror(iv) X isor(v) X isRis selected from Cl and F and Ris H; or Ris H and Ris selected from Cl, F, —CH, ...

Method of treating contrast-induced nephropathy

The present invention provides the use of a neutral endopeptidase inhibitor, in the manufacture of a medicament for the treatment, amelioration and/or prevention of contrast-induced nephropathy. The invention also relates to the use of a compound of Formula I: wherein R 1 , R 2 , R 3 , R 5 , X, A 3 , B 1 , s and n are defined herein, for the treatment, amelioration and/or prevention of contrast-induced nephropathy. The present invention further provides a combination of pharmacologically active agents for use in the treatment, amelioration and/or prevention of contrast-induced nephropathy.

COMPOUNDS WITH ANTIMICROBIAL ACTIVITY

This invention relates to compounds of formula 1, 2 or 3 3. A pharmaceutical composition for treatment or prevention of bacterial or protozoal infections claim 1 , comprising the compound of .4. The pharmaceutical composition of claim 3 , wherein said pharmaceutical composition is in the form of tablets claim 3 , capsules claim 3 , lozenges claim 3 , troches claim 3 , hard candies claim 3 , powders claim 3 , sprays claim 3 , creams claim 3 , salves claim 3 , suppositories claim 3 , jellies claim 3 , gels claim 3 , pastes claim 3 , lotions claim 3 , ointments claim 3 , aqueous suspensions claim 3 , injectable solutions claim 3 , elixirs claim 3 , or syrups.5. The pharmaceutical composition of claim 3 , wherein said pharmaceutical composition comprises 5% to 70% by weight of said compound.6Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, Escherichia coliStreptococcus pneumoniae.. The pharmaceutical composition of claim 3 , wherein said bacterial or protozoal infections are caused by microorganism selected from the group consisting of claim 3 , and7. A method to inhibit NusB-NusE interaction in a microorganism claim 1 , comprising the step of contacting the compound of with said microorganism.8. The method of claim 7 , wherein said NusB is selected from NusB E81 claim 7 , NusB Y18 and NusB E75 claim 7 , and NusE is selected from NusE H15 claim 7 , NusE D19 and NusE R16.9Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, Escherichia coliStreptococcus pneuroniae.. The method of claim 7 , wherein said microorganism is selected from the group consisting of claim 7 , and10. A method of treating or preventing bacterial or protozoal infections in a subject claim 1 , comprising a step of administering a therapeutically effective amount of the compound of to said subject.11. The method of claim 10 , ...

Neprilysin inhibitors

In one aspect, the invention relates to compounds having the formula: where R 1 -R 6 , a, b, Z, 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.

ACSS2 INHIBITORS AND METHODS OF USE THEREOF

The present invention relates to novel ACSS2 inhibitors having activity as anti-cancer therapy, treatment of alcoholism, and viral infection (e.g., CMV), composition and methods of preparation thereof, and uses thereof for treating viral infection, alcoholism, alcoholic steatohepatitis (ASH), non-alcoholic steatohepatitis (NASH), obesity/weight gain, anxiety, depression, post-traumatic stress disorder, inflammatory/autoimmune conditions and cancer, including metastatic cancer, advanced cancer, and drug resistant cancer of various types. 6. The compound of claim 2 , wherein Ris CFCHCH claim 2 , Ris OCH claim 2 , Ris CHor any combination thereof.8. The compound of claim 1 , wherein the compound is an Acyl-CoA Synthetase Short-Chain Family Member 2 (ACSS2) inhibitor.9. A method of treating claim 1 , suppressing claim 1 , reducing the severity claim 1 , reducing the risk of developing or inhibiting cancer comprising administering a compound according to to a subject suffering from cancer under conditions effective to treat claim 1 , suppress claim 1 , reduce the severity claim 1 , reduce the risk of developing claim 1 , or inhibit said cancer.10. The method of claim 9 , wherein the cancer is selected from the list of: hepatocellular carcinoma claim 9 , melanoma (e.g. claim 9 , BRAF mutant melanoma) claim 9 , glioblastoma claim 9 , breast cancer (e.g. claim 9 , invasive ductal carcinomas of the breast claim 9 , triple-negative breast cancer) claim 9 , prostate cancer claim 9 , liver cancer claim 9 , brain cancer claim 9 , ovarian cancer claim 9 , lung cancer claim 9 , Lewis lung carcinoma (LLC) claim 9 , colon carcinoma claim 9 , pancreatic cancer claim 9 , renal cell carcinoma and mammary carcinoma.11. The method of claim 9 , wherein the cancer is early cancer claim 9 , advanced cancer claim 9 , invasive cancer claim 9 , metastatic cancer claim 9 , drug resistant cancer or any combination thereof.12. The method of claim 9 , wherein the subject has been previously ...

SMALL MOLECULE INHIBITORS OF LACTATE DEHYDROGENASE AND METHODS OF USE THEREOF

Provided is a compound of formula (I) [Formula (I) should be inserted here], in which Ar, R, U, V, W, X, and p are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer, a method of treating a patient with cancer cells resistant to an anti-cancer agent, and a method of inhibiting lactate dehydrogenase A (LDHA) and/or lactate dehydrogenase B (LDHB) activity in a cell. 23-. (canceled)4. The compound or salt of claim 1 , wherein{'sup': '1', 'sub': 2', '2', '2', '1', '4', '1', '4', '1', '2', '1', '2', '2', '1', '6, 'Ris independently chosen from hydroxyl, halo, —COH, —SONH, C-Calkyl, C-Calkoxy, C-Chaloalkyl optionally substituted with halo, C-Chaloalkoxy, and —CO(C-Calkyl),'}{'sup': 2', '2, 'sub': 2', '2', '2', '2, 'Ris chosen from F and —SONH, where one of Ris —SONH;'}{'sup': '3', 'Ris independently chosen from'}{'sub': '5', '(a) halogen, hydroxyl, SF;'}{'sub': 1', '6', '2, '(b) C-Chydrocarbyl where any alkylene (CH) group in the hydrocarbyl chain is optionally replaced with NH, O, or S;'}{'sub': 0', '2', '0', '2', '0', '2', '0', '2', '0', '2', '0', '2', '0', '2', '3', '6', '0', '2', '3', '6', '0', '2', '3', '6', '0', '2', '3', '6', '0', '2', '0', '2', '0', '2', '2', '0', '2, 'claim-text': [{'sub': 1', '2', '1', '2, 'where each of (b) is unsubstituted or substituted with 1 or more substituents independently chosen from halogen, hydroxyl, cyano, amino, C-Chaloalkyl, and C-Chaloalkoxy;'}, {'sub': 1', '4', '1', '6', '1', '4', '1', '4', '1', '2', '1', '2, 'where each of (c) is unsubstituted or substituted with 1 or more substituents independently chosen from halogen, hydroxyl, cyano, amino, C-Calkyl, C-Ccycloalkyl, mono- or di-C-Calkylamino, C-Calkoxy, C-Chaloalkyl, and C-Chaloalkoxy;'}], '(c) —C-Chydrocarbyl (phenyl), —C-Chydrocarbyl (phenyl), —C-Chydrocarbyl (thiophenyl), —C-Chydrocarbyl (oxazolyl), —C-Chydrocarbyl(thiazolyl), —C-Chydrocarbyl (tetrahydrofuranyl), —C-Chydrocarbyl(C-Ccycloalkyl), —C- ...

PYRAZOLE COMPOUND

The present invention relates to a novel serotonin reuptake inhibitor which also exhibits 5-HTantagonistic action (antidepressive and anxiolytic effects), in particular, 5-HTinverse agonistic action comprising Compound (1): 117-. (canceled)18. A compound selected from the group consisting of:a) 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine;b) 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine; andc) N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine,or a pharmaceutically acceptable salt thereof.19. The compound of claim 18 , wherein the compound is 1-{1-(cyclopentylmethyl)-5-[(2 claim 18 ,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine claim 18 , or a pharmaceutically acceptable salt thereof.20. The compound of claim 18 , wherein the compound is 1-{5-[(2 claim 18 ,5-difluorobenzyl)oxy]-1-(3 claim 18 ,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine claim 18 , or a pharmaceutically acceptable salt thereof.21. The compound of claim 18 , wherein the compound is N-methyl-1-{1-(3-methylbutyl)-5-[(2 claim 18 ,4 claim 18 ,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine claim 18 , or a pharmaceutically acceptable salt thereof.22. A citrate of a compound selected from the group consisting of:a) 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine;b) 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine;c) N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine.23. The citrate of claim 22 , wherein the compound is 1-{1-(cyclopentylmethyl)-5-[(2 claim 22 ,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine.24. The citrate of claim 22 , wherein the compound is 1-{5-[(2 claim 22 ,5-difluorobenzyl)oxy]-1-(3 claim 22 ,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine.25. The citrate of claim 22 , wherein the compound is N-methyl ...

HYDROXY ISOXAZOLE COMPOUNDS USEFUL AS GPR120 AGONISTS

The present invention relates to a compound represented by formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing diabetes, hyperlipidemia, obesity, NASH, inflammation related disorders, and related diseases and conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR120. Pharmaceutical compositions and methods of treatment are also included. 2. The compound of wherein A is aryl claim 1 , wherein aryl is unsubstituted or substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substituents selected from R; or a pharmaceutically acceptable salt thereof.3. The compound of wherein A is heteroaryl claim 1 , wherein heteroaryl is unsubstituted or substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substituents selected from R; or a pharmaceutically acceptable salt thereof.6. The compound of wherein Ris halogen; or a pharmaceutically acceptable salt thereof.7. The compound of wherein Ris hydrogen; or a pharmaceutically acceptable salt thereof.8. The compound of wherein Ris selected from:(1) halogen, and{'sub': '1-6', '(2) —Calkyl,'}{'sub': 2', '1-6', '1-6', '2', '1-6, 'wherein each alkyl is unsubstituted or substituted with 1-3 substituents selected from: halogen, OH, —NH, —NH(Calkyl), —N(Calkyl)and —OCalkyl;'}or a pharmaceutically acceptable salt thereof.9. The compound of wherein Ris halogen; or a pharmaceutically acceptable salt thereof.13. A pharmaceutical composition comprising a compound of in combination with a pharmaceutically acceptable carrier.14. (canceled)15. (canceled)16. (canceled)17. A method for the treatment of a condition selected from the group consisting of diabetes claim 1 , hyperlipidemia claim 1 , obesity claim 1 , and inflammation related disorders comprising administering to an individual a pharmaceutical composition comprising the compound of . The present invention relates to substituted chromane derivatives that are useful in the pharmaceutical field. The compounds act as ...

MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The present invention features a compound of formula I: 1185.-. (canceled)187. The compound of claim 186 , wherein ring B is phenyl claim 186 , pyridyl claim 186 , pyridine-2(1H)-one claim 186 , pyrazole claim 186 , indole claim 186 , aza-indole claim 186 , thiophene claim 186 , dihydrobenzofuran claim 186 , or quinoline.189. The compound of claim 186 , wherein ring C is selected from indole claim 186 , piperidine claim 186 , azepane claim 186 , azetadine claim 186 , indoline claim 186 , isoindoline claim 186 , or pyrrolidine.191. The compound of claim 186 , wherein Ris halo claim 186 , CN claim 186 , C1-C6 alkyl claim 186 , C1-C6 alkoxy claim 186 , C3-C8 cycloalkyl claim 186 , or a phenyl claim 186 , pyridyl claim 186 , pyrimidine claim 186 , indole claim 186 , aza-indole claim 186 , pyrazole claim 186 , or thiophene ring claim 186 , or a (C1-C9 alkylene)-Rwherein up to four CHunits are independently replaced with O claim 186 , CO claim 186 , S claim 186 , SO claim 186 , SOor NR claim 186 , wherein all rings are optionally substituted with one or more groups selected from halo claim 186 , C1-C6 alkyl claim 186 , C1-C6 alkoxy claim 186 , C1-C6 fluoroalkyl claim 186 , C1-C6 fluoroalkoxy claim 186 , OH claim 186 , CHOH claim 186 , CHOCH claim 186 , CN claim 186 , COH claim 186 , amino claim 186 , amido claim 186 , C3-C10 heteroaryl claim 186 , and C3-C10 heterocycloalkyl.193. The compound of claim 186 , wherein Ris selected from halo claim 186 , OH claim 186 , CN claim 186 , azide claim 186 , amino claim 186 , C1-C6 alkyl or fluoroalkyl claim 186 , C1-C6 alkoxy or fluoroalkoxy claim 186 , C3-C10 heterocyclic ring wherein up to 4 ring atoms are independently O claim 186 , S claim 186 , N claim 186 , or NR; or a (C1-C9 alkylene)-Rwherein up to four CHunits are independently replaced with O claim 186 , CO claim 186 , S claim 186 , SO claim 186 , SOor NR.195. The compound of claim 186 , wherein Ris selected from halo claim 186 , CN claim 186 , C1-C6 alkyl or fluoroalkyl ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 130-. (canceled)32. The method of claim 31 , wherein the disease is selected from hypertension claim 31 , heart failure claim 31 , and renal disease.33. The method of claim 31 , further comprising administering a therapeutic agent selected from an adenosine receptor antagonist claim 31 , an α-adrenergic receptor antagonist claim 31 , a β-adrenergic receptor antagonist claim 31 , a β-adrenergic receptor agonist claim 31 , a dual-acting β-adrenergic receptor antagonist/α-receptor antagonist claim 31 , an advanced glycation end product breaker claim 31 , an aldosterone antagonist claim 31 , an aldosterone synthase inhibitor claim 31 , an aminopeptidase N inhibitor claim 31 , an androgen claim 31 , an angiotensin-converting enzyme inhibitor claim 31 , a dual-acting angiotensin-converting enzyme/neprilysin inhibitor claim 31 , an angiotensin-converting enzyme 2 activator claim 31 , an angiotensin-converting enzyme 2 stimulator claim 31 , an angiotensin-II vaccine claim 31 , an anticoagulant claim 31 , an anti-diabetic agent claim 31 , an antidiarrheal agent claim 31 , an anti-glaucoma agent claim 31 , an anti-lipid agent claim 31 , an antinociceptive agent claim 31 , an anti-thrombotic agent claim 31 , an ATreceptor antagonist claim 31 , a dual-acting ATreceptor antagonist/neprilysin inhibitor claim 31 , a multifunctional angiotensin receptor blocker claim 31 , a bradykinin receptor antagonist claim 31 , a calcium channel blocker claim 31 , a chymase inhibitor claim 31 , digoxin claim 31 , a diuretic claim 31 , a dopamine agonist claim 31 , an endothelin converting enzyme inhibitor claim 31 , an endothelin receptor antagonist claim 31 , HMG-CoA reductase inhibitor claim 31 , an estrogen claim 31 , an estrogen receptor agonist claim 31 , an estrogen receptor antagonist claim 31 , a monoamine reuptake inhibitor claim 31 , a muscle relaxant claim 31 , a natriuretic peptide claim 31 , a natriuretic peptide ...

SUBSTITUTED HETEROCYCLES AS c-MYC TARGETING AGENTS

Disclosed are substituted heterocycle compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders. 2. The compound of claim 1 , wherein at least one of Rand Ris an aryl group claim 1 , a benzyl group claim 1 , a heteroaryl group claim 1 , a cycloalkyl group claim 1 , or a cycloheteroalkyl group claim 1 , and Rand Roptionally are substituted at one or more positions with one or more of alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , hydroxyl claim 1 , halo claim 1 , cyano claim 1 , amido claim 1 , hydrazonyl claim 1 , carbonyl claim 1 , carboxyl claim 1 , and alkoxycarbonyl.3. The compound of claim 1 , wherein m is 0 and Ris hydrogen; or wherein Ris hydrogen.4. The compound of claim 1 , wherein Ris an aryl group claim 1 , a benzyl group claim 1 , a heteroaryl group claim 1 , a cycloalkyl group claim 1 , or a cycloheteroalkyl group claim 1 , and Roptionally is substituted at one or more positions with one or more of alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , hydroxyl claim 1 , halo claim 1 , cyano claim 1 , amido claim 1 , hydrazonyl claim 1 , carbonyl claim 1 , carboxyl claim 1 , and alkoxycarbonyl; and wherein Ris hydrogen.5. The compound of claim 1 , wherein m is 0 and Ris hydrogen; and wherein Ris an aryl group claim 1 , a benzyl group claim 1 , a heteroaryl group claim 1 , a cycloalkyl group claim 1 , or a cycloheteroalkyl group claim 1 , and Roptionally is substituted at one or more positions with one or more of alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , hydroxyl claim 1 , halo claim 1 , cyano claim 1 , amido claim 1 , hydrazonyl claim 1 , carbonyl claim 1 , carboxyl claim 1 , and alkoxycarbonyl.14. A pharmaceutical composition comprising a compound of and a suitable ...

NOVEL FUNGICIDAL HETEROCYCLIC COMPOUNDS

The present invention relates to a compound selected from Formula I and a process for preparing the same, 3. The compound as claimed in claim 1 , wherein claim 1 ,T is T1 to T47;G is G1 to G63;J is J1 to J82; andQ is Q1 to Q99.4. The compound as claimed in claim 1 , wherein claim 1 ,T is selected from T11, T25, T26, T37, T38, and T39;G is selected from G1, G15, G37, G45, G61;J is selected from J30, J11 and J29; andQ is Q45, Q32, Q33, Q34, Q36, Q38 and Q39.5. The compound as claimed in claim 1 , comprising1-(4-(4-(5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)-2-((1-methyl-1H-pyrazol-3-yl)oxy)ethan-1-one; 1-(4-(4-(5-(2,6-dichlorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)-2-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)oxy)ethan-1-one; 1-(4-(4-(5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)-2-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)oxy)ethan-1-one; 3-chloro-2-(3-(2-(1-(2-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)oxy)acetyl)piperidin-4-yl)thiazol-4-yl)-4,5-dihydroisoxazol-5-yl)phenylmethanesulfonate; 3-chloro-2-(3-(2-(1-(2-((1-methyl-1H-pyrazol-3-yl)oxy)acetyl)piperidin-4-yl)thiazol-4-yl)-4,5-dihydroisoxazol-5-yl)phenylmethanesulfonate; 1-(4-(4-(5-(2,6-dichlorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)-2-((5-(difluoromethyl)-1-methyl-1H-pyrazol-3-yl)oxy)ethan-1-one; 2-((5-(difluoromethyl)-1-methyl-1H-pyrazol-3-yl)oxy)-1-(4-(4-(5-(2,4,6-trichlorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)ethan-1-one; 3-chloro-2-(3-(2-(1-(2-((5-(difluoromethyl)-1-methyl-1H-pyrazol-3-yl)oxy)acetyl)piperidin-4-yl)thiazol-4-yl)-4,5-dihydroisoxazol-5-yl)phenylmethanesulfonate; 2-((5-(difluoromethyl)-1-methyl-1H-pyrazol-3-yl)oxy)-1-(4-(4-(5-(2,6-di fluorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)ethan-1-one; 2-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)oxy)-1-(4-(4-(5-(2,4,6-trichlorophenyl)-4, 5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1- ...

SUBSTITUTED BICYCLIC COMPOUNDS

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

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 130-. (canceled)32. The compound claim 31 , salt or stereoisomer of claim 31 , wherein Ris —Calkyl.33. The compound claim 31 , salt or stereoisomer of claim 31 , wherein Ris selected from —CHand —CHCH.34. The compound claim 31 , salt or stereoisomer of claim 31 , wherein Ris —CHCH.35. The compound claim 31 , salt or stereoisomer of claim 31 , wherein Ris —OH.36. The compound claim 34 , salt or stereoisomer of claim 34 , wherein Ris —OH.37. The compound claim 31 , salt or stereoisomer of claim 31 , wherein Ris H or —Calkyl.38. The compound claim 31 , salt or stereoisomer of claim 31 , wherein Ris H.39. The compound claim 34 , salt or stereoisomer of claim 34 , wherein Ris H.40. The compound claim 36 , salt or stereoisomer of claim 36 , wherein Ris H.41. The compound claim 34 , salt or stereoisomer of claim 34 , wherein Ris F and Ris Cl.42. The compound claim 36 , salt or stereoisomer of claim 36 , wherein Ris F and Ris Cl.43. The compound claim 39 , salt or stereoisomer of claim 39 , wherein Ris F and Ris Cl.44. A pharmaceutical composition comprising the compound claim 31 , salt or stereoisomer of and a pharmaceutically acceptable carrier.45. A pharmaceutical composition comprising the compound claim 40 , salt or stereoisomer of and a pharmaceutically acceptable carrier.46. A pharmaceutical composition comprising the compound claim 43 , salt or stereoisomer of and a pharmaceutically acceptable carrier.47. The pharmaceutical composition of claim 45 , wherein the pharmaceutically acceptable carrier is magnesium stearate.48. The pharmaceutical composition of claim 46 , wherein the pharmaceutically acceptable carrier is magnesium stearate.49. An oral dosage form comprising the compound claim 40 , salt or stereoisomer of .50. An oral dosage form comprising the compound claim 43 , salt or stereoisomer of . This application claims the benefit of U.S. Provisional Application No. 61/680,804, filed on Aug. ...

SUBSTITUTED BICYCLIC COMPOUNDS

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

AMINOINDANE-, AMINOTETRAHYDRONAPHTHALENE- AND AMINOBENZOCYCLOBUTANE-DERIVED PRMT5-INHIBITORS

A compound of formula (1a), (1b) or (1c) wherein: n is 1 or 2; Ris H or Me; Ris optionally one or more halo or methyl groups; Rand Rare independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CHOH; Rand R(if present) are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CHOH; Rand Rare independently selected from H and Me; Ris selected from OH, —NH, —C(═O)NH, and —CHOH; Ris either H or Me; Ris either H or Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted Cheteroaryl. 26-. (canceled)7. A compound according to claim 1 , wherein Rrepresents one to four Me or halo groups.8. A compound according to claim 1 , wherein:{'sup': 2a', '2b', '2c', '2d, '(a) R, R, Rand R(if present) are all H; or'}{'sup': 2a', '2b', '2c', '2d, 'sub': '2', '(b) of formula Ia or Ib, wherein R, R, Rand Rare comprised of three H and one Me or CHOH group; or'}{'sup': 2a', '2b', '2c', '2d, '(c) of formula Ia or Ib, wherein R, R, Rand Rare comprised of two H and two Me groups; or'}{'sup': 2a', '2b, 'sub': '2', '(d) of formula Ic, wherein Ris H and Ris a Me or CHOH group; or'}{'sup': 2a', '2b, 'sub': '2', '(e) of formula Ic, wherein Rand Rare each a Me or CHOH group.'}917-. (canceled)18. A compound according to claim 1 , wherein:{'sup': 3a', '3b, '(a) Ris H and Ris Me, or'}{'sup': 3a', '3b, '(b) Rand Rare both H, or'}{'sup': 3a', '3b, '(c) Rand Rare both Me.'}1925.-. (canceled)28. A compound according to claim 1 , wherein the compound is a racemate at the carbon atom to which Rand Rare attached.29. A compound according to claim 1 , wherein the compound is a single enantiomer at the carbon atom to which Rand Rare attached.3031-. (canceled)32. A compound according to claim 1 , wherein the optional substituents on A are independently selected from the group consisting of: Calkyl claim 1 , Cfluoroalkyl claim 1 , Ccycloalkyl claim 1 , Cheteroaryl claim 1 , Cheteroaryl ...

PYRAZOLE COMPOUND

The present invention relates to a novel serotonin reuptake inhibitor which also exhibits 5-HTantagonistic action (antidepressive and anxiolytic effects), in particular, 5-HTinverse agonistic action comprising Compound (1): 117-. (canceled)19. The method of claim 18 , wherein R claim 18 , R claim 18 , and Rare independently selected from the group consisting of a hydrogen atom and a methyl group claim 18 , and Ris a hydrogen atom.20. The method of claim 18 , wherein A is an optionally-substituted Caryl group.21. The method of claim 18 , wherein X is a hydrogen atom.22. The method of claim 18 , wherein L is an oxygen atom.23. The method of claim 18 , wherein n is 1.24. The method of claim 18 , wherein R claim 18 , R claim 18 , and Rare hydrogen atoms claim 18 , and Ris a methyl group.25. The method of claim 18 , wherein R claim 18 , R claim 18 , R claim 18 , and Rare hydrogen atoms.26. The method of claim 18 , wherein E is an optionally-substituted Ccycloalkyl group claim 18 , an optionally-substituted 5- to 10-membered saturated heterocyclic group containing 1 to 3 oxygen atoms as a constituent atom of the ring claim 18 , or an optionally-substituted phenyl group.27. The method of claim 18 , wherein E is an optionally-substituted Ccycloalkyl group.28. The method of claim 18 , wherein r is 1 or 2.29. The method of claim 18 , wherein Ris an optionally-substituted Calkyl group.30. The method of claim 18 , wherein the compound of Formula (1) or a pharmaceutically acceptable salt thereof is at least one selected from the group consisting of:1-[5-(benzyloxy)-1-(cyclohexylmethyl)-1H-pyrazol-3-yl]-N-methylmethanamine;1-{1-(cyclohexylmethyl)-5-[(2-fluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine;1-{1-(cyclohexylmethyl)-5-[(3-fluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine;1-{1-(cyclohexylmethyl)-5-[(4-fluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine;1-{5-[(2-chlorobenzyl)oxy]-1-(cyclohexylmethyl)-1H-pyrazol-3-yl}-N-methylmethanamine;1-{5-[(3-chlorobenzyl) ...

ANTIDIABETIC COMPOUNDS

Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia. 3. The compound according to wherein T claim 1 , U claim 1 , V and W are CH; or a pharmaceutically acceptable salt thereof.5. The compound according to wherein A is —Ccycloheteroalkyl claim 1 , wherein each cycloheteroalkyl is unsubstituted or substituted with one claim 1 , two or three substituents selected from R; or a pharmaceutically acceptable salt thereof.10. The compound according to wherein Y is selected from: —O— claim 1 , —(CH)O— and —O—(CH) claim 1 , wherein CHis unsubstituted or substituted with one or two substituents selected from R; or a pharmaceutically acceptable salt thereof.11. The compound according to wherein Y is selected from: —O— claim 1 , —CH—O— claim 1 , and —O—CH— wherein CHis unsubstituted or substituted with one or two substituents selected from Calkyl; or a pharmaceutically acceptable salt thereof.12. The compound according to wherein Y is —(CH)O— claim 1 , wherein CHis unsubstituted or substituted with one or two substituents selected from R; or a pharmaceutically acceptable salt thereof.13. The compound according to wherein Y is selected from: —O— and —CH—O— claim 1 , wherein CHis unsubstituted or substituted with one or two substituents selected from Calkyl; or a pharmaceutically acceptable salt thereof.15. The compound according to wherein Z is —COH; or a pharmaceutically acceptable salt thereof.19. The compound according to wherein Ris —Ccycloalkyl claim 1 , ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula XII: 128-. (canceled)29. A compound of:(a) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic acid;(b) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic acid ethoxycarbonyloxymethyl ester;(c) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic acid isopropoxycarbonyloxymethyl ester;(d) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic acid acetoxymethyl ester;(e) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic acid (S)-2-methoxycarbonylamino-3-methylbutyryloxymethyl ester; ora pharmaceutically-acceptable salt thereof.30. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .31. A method for treating hypertension claim 29 , heart failure claim 29 , or renal disease claim 29 , comprising administering to a patient a therapeutically effective amount of the compound of . 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, pulmonary hypertension, and renal disease.Commonly-assigned U.S. Patent Publication No. 2012/0157383, filed on Dec. 14, 2011 to Gendron et al., describes novel compounds that have activity as neprilysin inhibitors, the ...

Treatment of Amyotrophic Lateral Sclerosis

The present invention relates to the identification of compounds and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided compounds. 112.-. (canceled)18. The compound of claim 13 , wherein Ris selected from H and alkyl moieties.19. The compound of claim 13 , wherein Ris selected from H and alkyl moieties.20. The compound of claim 13 , wherein Ris selected from H and alkyl moieties.21. The compound of claim 13 , wherein Ris selected from H and alkyl moieties.22. The compound of claim 13 , wherein Ar is phenyl or naphthyl optionally substituted at one or more positions with alkyl claim 13 , amino claim 13 , alkylamino claim 13 , alkylsulfonyl claim 13 , alkylcarbonyl claim 13 , alkoxy claim 13 , alkoxycarbonyl claim 13 , cyano claim 13 , or halo moieties.23. The compound of claim 13 , wherein Ar is phenyl or naphthyl optionally substituted at one or more positions with halo moieties.25. A pharmaceutical composition comprising the compound of and a carrier component.26. A method of treating a neurodegenerative disease in a subject in need thereof claim 13 , the method comprising administering the pharmaceutical composition of to the subject.27. A method of claim 26 , wherein the neurodegenerative disease is characterized by the presence of aberrant protein aggregates.28. The method of claim 26 , wherein the neurodegenerative disease is amyotrophic lateral sclerosis (ALS).29. The method of claim 26 , wherein the neurodegenerative disease is Alzheimer's Disease.30. The method of claim 26 , wherein the neurodegenerative disease is prion disease.31. The method of claim 14 , wherein the neurodegenerative disease is claim 14 , or Huntington's Disease. This application is a continuation of and claims priority to and the benefit of application Ser. No. 14/103,728 filed Dec. 11, 2013 and issued as U.S. Pat. No. 9,145,424 on Sep. 29, ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 130-. (canceled)32: A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .33: A pharmaceutical composition comprising a pharmaceutically acceptable carrier claim 31 , a compound of claim 31 , and an ATreceptor antagonist.34: The pharmaceutical composition comprising a pharmaceutically acceptable carrier claim 31 , a compound of claim 31 , and a phosphodiesterase (PDE) inhibitor.35: The pharmaceutical composition comprising a pharmaceutically acceptable carrier claim 31 , a compound of claim 31 , and a renin inhibitor.36: The pharmaceutical composition comprising a pharmaceutically acceptable carrier claim 31 , a compound of claim 31 , and a diuretic.37: A method for treating hypertension claim 31 , heart failure claim 31 , or renal disease claim 31 , comprising administering to a patient a therapeutically effective amount of the compound of . This application claims the benefit of U.S. Provisional Application No. 61/680,804, filed on Aug. 8, 2012 and U.S. Provisional Application No. 61/774,163, filed on Mar. 7, 2013; the entire disclosures of which are incorporated herein by reference.The present invention relates to novel compounds having neprilysin-inhibition activity or which are metabolized in vivo to compounds having such activity. 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.Commonly-assigned U.S. Patent Publication No. 2012/0213806, filed on Feb. 16, 2012 to Fleury 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 ...

Phenoxymethyl derivatives

wherein RA, RB, RC, RC1 and W are as defined herein, compositions including the compounds and methods of using the compounds.

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula XII: 128-. (canceled)29. A compound of:(a) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-methoxyisoxazole-5-carbonyl)amino]pentanoic acid;(b) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-methoxyisoxazole-5-carbonyl)amino]pentanoic acid 2-methoxycarbonylamino-3-methylbutyryloxymethyl ester;(c) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-methoxyisoxazole-5-carbonyl)amino]pentanoic acid isopropoxycarbonyloxymethyl ester;(d) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-methoxyisoxazole-5-carbonyl)amino]pentanoic acid acetoxymethyl ester;(e) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-methoxyisoxazole-5-carbonyl)-amino]pentanoic acid ethoxycarbonyloxymethyl ester; ora pharmaceutically-acceptable salt thereof. 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, pulmonary hypertension, and renal disease.Commonly-assigned U.S. Patent Publication No. 2012/0157383, filed on Dec. 14, 2011 to Gendron 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, ...