СОЕДИНЕНИЯ ДЛЯ ЛЕЧЕНИЯ НЕКОТОРЫХ ЛЕЙКОЗОВ

Изобретение относится к соединениям формулы (I) или (Ia), ингибирующим ферментативную тирозинкиназную активность белка, выбранного из белка Абельсона (ABL1), Абельсон-родственного белка (ABL2) или химерного белка BCR-ABL1, их композиции, способам ингибирования ферментативной тирозинкиназной активности белка, выбранного из белка Абельсона (ABL1), Абельсон-родственного белка (ABL2) или химерного белка BCR-ABL1, и способам лечения заболеваний, при которых модуляция активности BCR-ABL1 предотвращает, подавляет или ослабляет патологию и/или симптоматику заболевания. Технический результат: получены новые соединения, которые обладают ингибирующей ферментативной тирозинкиназной активности белка, выбранного из белка Абельсона (ABL1), Абельсон-родственного белка (ABL2) или химерного белка BCR-ABL1. 6 н. и 18 з.п. ф-лы, 2 табл., 232 пр.

ПРОИЗВОДНЫЕ БЕНЗИМИДАЗОЛА В КАЧЕСТВЕ МОДУЛЯТОРОВ ROR-ГАММА

Изобретение относится к области органической химии, а именно к циклическому соединению формулы (I) или к его фармацевтически приемлемой соли, где X представляет собой –C(O)NH- или –NHC(O)-; R1выбран из (C1–C4)алкила, галоген(C1–C4)алкила, циклобутила, тетрагидрофуранила, (C1–C4)алкокси, -N((C1–C3)алкил)2, -(C1–C3)алкил-O-(C1–C2)алкила, -C(O)O(C1–C2)алкила и циклопропила, причем каждый из указанных циклобутила и циклопропила необязательно замещен C(=O)OMe, -CN или 1 галогеном; L2представляет собой CH2или CHMe; Cy1выбран из фенила, пиридила и пиперидинила, каждый из которых необязательно замещен 1-2 группами, которые независимо выбирают из R5; Cy2выбран из гетероциклических структур, указанных в п. 1, каждый из которых необязательно замещен 1-2 группами, которые независимо выбирают из R6; R5выбран из галогена, -CN, -ORc, -S(O)2NRdReи -SO2Rb; R6выбирают из галогена, оксо и (C1–C4)алкила; R7представляет собой водород, ORcили (C1–C3)алкил, необязательно замещенный ORc; R8, при наличии, представляет ...

ПРОИЗВОДНЫЕ БЕНЗИМИДАЗОЛА, ИХ ТАУТОМЕРЫ ИЛИ ИХ СОЛИ И ЛЕКАРСТВЕННОЕ СРЕДСТВО С АНТАГОНИСТИЧЕСКИМ В ОТНОШЕНИИ АНГИОТЕНЗИНА II ДЕЙСТВИЕМ

Производные бензимидазола формулы I, где R1 - C1-3 - алкил, R2 - 5-, 6- или 7-членная алкилениминогруппа, в которой одна метиленовая группа заменена сульфонильной группой, незамещенная или замещенная в положении 1 алкилом бензимидазол - 2-ил или 4, 5, 6, 7-тетрагидробензимидазол - 2-ил, имидазо [1,2-a] пиридин-2-ил, 3-хлор-5, 6, 7, 8-тетрагидроимидазо [1,2-a] пиризин-2-ил; R3 - алкил, C3-5 - циклоалкил или алкоксил; R4 - замещенный в положении 1 и 2 Ra-CO-O-CH2-группой тетразолил, группа Rв-CO-O-(RcCH)-O-CO-RaO-CO- и RвO-CO-O(RcCH)-O-CO-, Ra и Rв- C1-6 - алкил, C5-7 - циклоалкил; Rс - водород или метил, их таутомеры или их соли. Соединения I расширяют ассортимент производных бензимидазола, обладающих антагонистическим в отношении ангиотензина II действием. 2 с.п. ф-лы, 1 табл.

ПРОИЗВОДНЫЕ ИМИДАЗОЛА, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Новые производные имидазолов, способ их получения; новые полученные промежуточные продукты, их применение в качестве медикаментов и содержащие их фармацевтические соединения. Предложены новые производные имидазолов, способ их получения и их использование в качестве лекарственных средств, использующихся в качестве ингибиторов действия ангиотензина II. Также предложен способ приготовления лекарственного средства. 3 с. и 2 з.п. ф-лы, 41 табл.

АНТАГОНИСТЫ РЕЦЕПТОРОВ ВЫСВОБОЖДАЮЩЕГО ГОНАДОТРОПИН ГОРМОНА

... 1. Соединение формулы I или его фармацевтически приемлемая соль, где A представляет арил или гетероарил, каждый из которых может быть необязательно замещен; B представляет (CR13R14)k-D; D представляет H, алкил, циклоалкил, гетероциклоалкил, арил или гетероарил, причем каждый из алкила, циклоалкила, гетероциклоалкила, арила или гетероарила может быть необязательно замещен; k представляет 0, 1, 2 или 3; R1 представляет H или необязательно замещенный алкил; R2, R3 и R4 независимо представляют H, необязательно замещенный алкил, галоген или OR1; R5, R6, R7, R8, R9, R10, R11 и R12 независимо представляют H, алкил, алкенил или алкинил, причем каждый из алкила, алкенила или алкинила может быть необязательно замещен; R13 и R14, каждый независимо, в случае присутствия, представляет H или необязательно замещенный алкил. 2. Соединение по п.1, где R1, R2, R3 и R4 независимо представляют Н или С1-С3 алкил. 3. Соединение по п.1 или 2, где R5, R6, R7, R8, R9, R10, R11 и R12 независимо представляют H, C1 ...

ВЕЩЕСТВА, ПРОЯВЛЯЮЩИЕ АНТИМИКРОБНУЮ, АНТИГРИБКОВУЮ, АНТИПРОТОЗОЙНУЮ АКТИВНОСТИ

Предложен новый класс соединений для борьбы с возбудителями бактериальной, протозойной и грибковой природы. Соединения являются производными гетеронитроалкенов (диоксолы, оксазолы, имидазолы) с указанными ниже структурными формулами и эффективны в отношении грамположительных бактерий и грамотрицательных аэробов, грибков рода Candida, Trichophyton и др., трихомонад. Они могут использоваться при лечении раневых инфекций, грибковых поражений, септических состояний, пневмонии, трахомы, орнитоза, сальмонеллеза, в том числе в ветеринарии. 5 н.п. ф-лы, 5 табл. 1. 1,3-бензодиоксол-5-β-нитроэтилен 2. 1,3-бензодиоксол-5-β-нитропропилен 3. бензимидазол-5-β-нитропропилен 4. 2-метилбензимидазол-5-β -нитроэтилен 5. бензоксазол-5-β-нитроэтилен 6. 2-метилбензоксазол-5-β-нитропропилен ...

СПОСОБ ПОЛУЧЕНИЯ 1-(2,7-ДИМЕТИЛ-2,7-ОКТАДИЕН-1-ИЛ)БЕНЗИМИДАЗОЛА

Изобретение относится к способу получения 1-(2,7-диметил-2,7-октадиен-1-ил)бензимидазола и может быть использовано в химической промышленности. Указанный способ получения 1-(2,7-диметил-2,7-октадиен-1-ил)бензимидазола из изопрена включает аллилирование бензимидазола, отличается тем, что изопрен подвергают взаимодействию с диалкиламином, таким как диметиламин, диэтиламин, пиперидин, морфолин, катализируемому Pd(acac)- PhP в растворе ТГФ, затем проводят кватернизацию полученного N-(2,7-диметил-2,7-октадиен-1-ил)диалкиламина действием этил- или метилйодида с образованием соответствующего йодида N-(2,7-диметил-2,7-октадиен-1-ил)триалкиламмония, действием которого на бензимидазол в присутствии KPOи палладиевого катализатора Pd(dba)в растворе ДМСО получают целевой 1-(2,7-диметил-2,7-октадиен-1-ил)бензимидазол. Предложен новый эффективный способ получения 1-(2,7-диметил-2,7-октадиен-1-ил)бензимидазола с высоким выходом и чистотой из доступного сырья, который не требует применения токсичных и взрывоопасных ...

СОЕДИНЕНИЯ АМИНА, ИМЕЮЩИЕ ПРОТИВОВОСПАЛИТЕЛЬНУЮ, ПРОТИВОГРИБКОВУЮ, ПРОТИВОПАРАЗИТАРНУЮ И ПРОТИВОРАКОВУЮ АКТИВНОСТЬ

АЦИЛИРОВАННЫЕ ИНДАНИЛАМИНЫ И ИХ ИСПОЛЬЗОВАНИЕ В КАЧЕСТВЕ ФАРМАЦЕВТИЧЕСКИХ СРЕДСТВ

... 1. Ацилированный инданиламин общей формулы (I) в любой из его стереоизомерных форм или их смесей в любом соотношении или его фармацевтически приемлемая соль где R1 и R4, независимо выбраны из группы, состоящей из Н; незамещенных и, по меньшей мере, монозамещенных С1-С10-алкила, С2-С10-алкенила и С2-С10-алкинила, заместители которых выбраны из группы, состоящей из F, OH, С1-С8-алкокси, (С1-С8-алкил)меркапто, CN, COOR6, CONR7R8 и незамещенных и, по меньшей мере, монозамещенных фенила и гетероарила, заместители которых выбраны из группы, состоящей из галогенов, псевдогалогенов, С1-С3-алкила, С1-С3-алкокси и CF3; R9CO; CONR10R11; COOR12; CF3; галогенов; псевдогалогенов; NR13R14; OR15; S(O)mR16; SO2NR17R18 и NO2; R2 и R3 независимо выбраны из группы, состоящей из Н; галогенов; псевдогалогенов, незамещенного и, по меньшей мере, монозамещенного С1-С10-алкила, заместители которого выбраны из группы, состоящей из ОН, фенила и гетероарила; ОН; C1-C10-алкокси; фенокси; S(O)m R19; CF3; CN; NO2; (С1 ...

Способ получения производных пиперазина или пиперидина или их солей

Способ получения 2-замещенных производных 1-циннамилбензимидазола

BENZIMIDAZOLDERIVATE MIT EINER WIRKUNG ALS ULKUSMITTEL.

Antithrombotische Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel

The invention relates to carboxylic acid amides of formula (I), in which R<1> to R<4>, Het, Z<1>, A, Ar, and m are defined as per claim 1, to their tautomers, their stereoisomers, their mixtures, their prodrugs and their salts, which exhibit valuable properties. The compounds of the aforementioned formula (I), in which R<4> represents a cyano group, represent valuable intermediate products for producing the remaining compounds of general formula (I), and the compounds of the aforementioned general formula (I), in which R<4> represents one of the amidino groups mentioned in claim 1, exhibit valuable pharmacological properties, in particular an anti-thrombotic action and a factor Xa inhibiting action.

Sensibilisierung von photographischen Silberhalogenidemulsionen

SULFONYLBENZIMIDAZOLDERIVATE

Electrophotographic materials

Photoconductive compositions as in Specification 964,873 use as photoconductive compounds pyrroles, pyrrolines, pyrrolidines, indoles, indolenines, indolines and naphthopyrrolines, including substituted derivatives and cyanine and merocyanine dyes derived from such. Many typical compounds are mentioned. The sensitizing dyestuffs, resins and auxiliary materials mentioned in Specification 964,873 may be used. Specified resins are polyvinyl formal and butyral, polyvinyl-carbazole and a terpolymer of vinyl chloride, vinyl acetate and maleic anhydride. Specifications 856,770, 883,312, 916,660 and 964,871 also are referred to.ALSO:A cyanine dye of the formula is made by reacting 3-ethyl-2-methyl-benzthiazolium iodide with N-methylisatin-a -anil. Specifications 344,409, 354,898, 428,222, 428,359, 428,360, 633,824, 856,770, 883,312, 916,660, 964,871 and 964,875 are referred to.

PHARMACEUTICALLY ACTIVE NITROSOUREA DERIVATIVES

... 1374344 Nitrosoureas and ureas SANKYO CO Ltd 20 Nov 1972 [20 Nov 1971 4 Dec 1971 26 July 1972] 53578/72 Heading C2C Novel compounds (I) of formula (including salts and hydrates thereof) wherein: A represents a group of the formula in which B is an unsaturated 5- or 6-membered heterocyclyl group containing at least one nitrogen hetero-atom, or an unsaturated 9- or 10-membered bicyclic fused-ring heterocyclyl group containing at least one nitrogen heteroatom, said heterocyclyl group optionally being ring-substituted with one or more alkyl, alkoxy, hydroxy, amino or hydroxyalkyl groups or halogen atoms; and Y is a methylene or ethylene group which may optionally be alkyl-substituted; or a group of the formula in which R1, R2, R3, R4, R5, R6, R7, R8 and R9 may be the same or different, and each represents a hydrogen atom or an alkyl group; or a group of the formula in which Z is an unsubstituted or alkyl-substituted ...

BENZIMIDAZOLYL SULPHIDES AND SULPHONES

... 1388041 Benzimidazoles E R SQUIBB & SONS Inc 29 Feb 1972 [4 March 1971] 9328/72 Heading C2C Novel compounds (I) (including salts thereof) where R is H, OH, alkoxy, NH 2 , alkylamino, NHCO 2 R5, alkyl, NO 2 , -SCN, halo, aralkyl, SH, aryl or alkylaryl, R1, R2, R21, R3 and R4 are H, alkyl, aralkyl or optionally substituted aryl, R5 is alkyl, aryl or cycloalkyl, m is 1 or 2, n is 0 or 1, n1 is 0 to 4, n + n1 is 4 or less and n2 is 0 or 1, are made by standard methods. Pharmaceutical preparations having anthelmintic action contain (I) as active ingredient. Administration is, e.g. orally.

BENZIMIDAZOLYL ISOTHIOCYANATES METHODS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING THEM

... 1435376 Benzimidazolyl - isothiocyanates E R SQUIBB & SONS Inc 31 May 1973 [2 June 1972] 26036/73 Heading C2C Novel compounds I and salts thereof in which R1 is hydrogen, C 1-7 alkyl optionally substituted by halogen or aryl as defined below, mono- or bi-cyclic aryl optionally substituted by halogen, NO 2 , CF 3 , alkoxy, optionally substituted amido or alkyl as defined above, alkoxycarbonyl, aryloxycarbonyl, dialkylaminoalkyl, acyl or carbamoyl or a 2-thiazolin-2-yl or 5,6 - dihydro - 4H - 1,3 - thiazin - 2 - yl radical optionally substituted by C 1-7 alkyl, halogen, di-C 1-7 alkylamino-alkyl or aryl as defined above. R2 is a saturated or unsaturated N, S or O containing heterocycle having 6 members and 1 and 2 hetero-atoms and optionally substituted by C 1-7 alkyl, halogen or di-C 1-7 alkylaminoalkyl and R3 is hydrogen, C 1-7 alkyl, halogen or C 1-7 alkoxy are prepared by reaction of a corresponding amino-benzimidazole (II) with a thiocarbamic derivative Hal-CS-Y ...

PROCESS FOR PREPARING QUATERNARY SALTS, NOVEL QUATERNARY SALTS AND PHOTOGRAPHIC EMULSIONS CONTAINING THEM

... 1283835 Heterocyclic quaternary salts EASTMAN KODAK CO 23 April 1970 [28 April 1969 (2)] 19547/70 Heading C2C [Also in Division G2] Novel heterocyclic quaternary salts of the formula in which Z represents the atoms required to complete a mono- or poly-nuclear heterocyclic ring system containing a 5- or 6-membered ring including the quaternary nitrogen atom, the atoms being selected from C, N, O, S and Se, n is 0 or 1, m is 0 or 1-4, X is an acid anion, R1 is hydrogen or an alkyl, aralkyl, aryl or alkylthio group, and R2 is a 1-hydrazono-C 1-5 -alkyl group, are prepared by reacting a salt of the formula with a compound of the formula where R6 is formyl, acetyl, propionyl, butyryl or pentanoyl, and condensing the intermediate carbonyl compound with a hydrazine having two hydrogen atoms attached to the same nitrogen atom. Specified hydrazine reactants include heterocyclic hydrazines, phenylhydrazines, in which the phenyl group may be substituted by alkyl, sulpho, ...

Pharmaceutically active ring fused imidazoles

Compounds of general formula I wherein the symbols are as defined in the specification, have endothelin antagonist activity and are therefore useful in treating cardiovascular disorders, such as hypertension, congestive heart failure, postischemic renal failure, vasospasm, cerebral and cardiac ischemia, myocardial infarction, inflammatory diseases, Raynaud's disease, and endotoxic shock, and asthma.

Compound

NEW BENZIMIDAZOLE COMPOUNDS AND PESTICIDAL PREPARATIONS CONTAINING THEM

... 1,223,623. Benzimidazoles. CIBA Ltd. 23 Oct., 1968 [26 Oct., 1967], No. 50365/68. Heading C2C. [Also in Division A5] Novel benzimidazoles of the formula in which R 1-3 represent hydrogen, halogen, alkyl, alkoxy, alkylthio, alkyl-SO-, alkyl- SO 2 -, nitro, cyano, trifluoro-methyl, formyl, -COOR1, -CONR1R11 or -SO 2 NR1R11, wherein R1 and R11 are hydrogen or C 1-4 alkyl, R 4 represents hydrogen or an aliphatic or cycloaliphatic group, other than perhalogenated aliphatic, X represents -O-, -S-, | -NH- or -Nalkyl and R 5 represents an aliphatic, araliphatic or aromatic group, are prepared by reacting a benzimidazole of the formula with a compound BR 5 , where A and B are groups which condense to form the group -CO-X-. Thus, the benzimidazole in which A is hydrogen may be reacted with an isocyanate or carbamic acid chloride to obtain the carbamates or with a chloroformate, or thio analogue, to obtain the carboxylic esters. A large ...

PROCESS FOR THE PRODUCTION OF SULPHOALKYL OR SULPHOALKENYLQUATERNARY SALTS

1-BENZAZOLYLALKYL-4-SUBSTITUTED-PIPERIDINES

A process and products for the improvement of the optical properties of organic material

Compounds of general formula in which A is an aromatic nucleus which may be substituted and in which 2 adjacent carbons are linked directly to B and the group B is sulphur or the group in which R1 is H or an organic substituent, R is an organic substituent, R2 is an organic substituent having at least 3 conjugated double bonds which are also in conjugation with the >C=N bond of the heterocyclic ring, and X is an acid residue, may be used in conjunction with washing agents for the treatment of organic materials. Suitable washing agents are, for example, soaps; salts of sulphonate washing agents, such as sulphonated benzimidazoles substituted on the 2-carbon atom by high alkyl radicals; salts of monocarboxylic acid esters of 4-sulphophthalic acid with high fatty alcohols; salts of fatty alcohol sulphonates; alkylaryl sulphonic acids; or condensation products of high fatty acids with aliphatic hydroxy or amino sulphonic acids.

Aryl or heteroaryl fused imidazole compounds as anti-inflammatory and analgesic agents

Succinamide inhibitors of interleukin-1beta converting enzyme.

Antiviral drugs for treatment of arenavirus infection

Benzimidazole compounds.

A range is disclosed of benzimidazole-4-carboxamide compounds (I) which can act as potent inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase or PARP enzyme (EC 2.4.2.30), and which thereby can provide useful therapeutic compounds for use in conjunction with DMA-damaging cytotoxic drugs or radiotherapy to potentiate the effects of the latter. In formula (I), R and R' may each be selected independently from hydrogen, alkyl, hydroxyalkyl (e.g. CH2CH2OH), acyl (e.g. acetyl or benzoyl) or an optionally substituted aryl (e.g. phenyl) or aralkyl (e.g. benzyl or carboxybenzyl) group. R is generally a substituted phenyl group in the most preferred compounds. The compounds may also be used in the form of pharmaceutically acceptable salts or pro-drugs.

COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS

Broadspectrum substituted benzimidazole sulfonamide HIV protease inhibitors.

The present invention concerns the compounds having the formula (1), wherein N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het1, Het2, R1 may also be radical of formula (R11AR11b)NC(R10aR10b)CR9-;t is 0, 1 or 2; R2 is H or C1-6alkyl; L is -C(=O)-, -O-C(=O)-, -NR8-C(=O)-, -O-C1-6alkanediyl-C(=O)-, -S(=O)2-,-O-S(=O)2-,-NR8-S(=O)2 ; R3 is C1-6 alkyl, aryl, C3-7 cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(=O), carboxyl, aminoC(=O), mono- or di(C1-4alkyl)aminoC(=O), C3-7cycloakyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; A is C1-6alkanediyl, -C(=O)-, -C(=S)-, -S(=O)2-, C1-6alkanediyl-C(=O)-, C1-6 alkanediyl-C(=S)- or C1-6akanediyl-S(=O)2-; is H, OH, C1-6alkyl, Het1C1-6alkyl, Het2C1-6alkyl, optionally substituted amino-C1-6alkyl; R6 is C1-6O, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6alkyloxycarbonylamino ...

Succinamide inhibitors of inteleukin-1B converting enzyme.

The present invention provides compounds of formula (i), pharmaceutical compositions comprising a compound of formula (i), and methods of treatment of stroke; infammatory diseases such as rheumatoid arthritis or inflammatory bowel disease; septic shock; reperfusion injury; alzheimer's disease; shigellosis; and multiple sclerosis.

Aryl or heteroaryl fused imidazole compounds as anti-inflammatory and analgesic agents.

This invention provides a compound of the formula (i); or the pharmaceutically acceptable salts thereof, wherein y1, y2, y3, and y4 are independently selected from n, ch, etc., r1 is h, c1-8 alkyl, etc., q1 is 5-12 membered monocyclic or bicyclic aromatic ring optonally containing up to 4 heteroatoms selected from o,n and s,etc., a is a 5-6 membered monocyclic aromatic ring optionally containing up to 3 heteroatoms selected from o,n and s,etc.;B is c1-6 alkylene optionally substituted with an oxo group, etc.; w is nh, o, etc.; r2 is h,c1-4 alkyl, etc.; z is a 5-12 membered monocyclic or bicyclic aromatic ring optionally containing up to 3 heteroatoms selected from o,n and s, etc.; l is halo, c1-4 alkyl,,etc.; m is0, 1 or 2; r3 and r4 are independently selected from o,n and s, etc.; l is halo, c1-4 alkyl ; r5 is h, c1-4 alkyl, etc.; q2 is a 5-12 membered monocyclic or bicyclic aromatic ring ortricyclic ring optionally containing up to 3 heteroatoms selected from o, n and s, etc. These compounds ...

Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors.

Susbtituted heteroaromatic compounds, and in particular substituted bicyclic heteroamromatic compounds of formula (i), wherein x is n or ch; a represents a fused 5, 6 or 7-membered heterocyclic ring containing 1 to 5 heteroatoms which may be the same or different and which are selected from n, o or s(o)m, wherein m is as defined above, the heterocyclic ring containing a of 1,2 or 3 double bonds inclusive of the bond in the pyridine or pyrimidine ring to which it is fused, with the provisos that the heterocyclic ring does not form part of a purine and that the fused heterocyclic ring does not contain two adjacent o ro s(o)m atoms. U represents a 5 to 10-membered mono or bicyclic ring system in which one or more of the carbon atoms is optionally replaced by a heteroatom independently selected from n,o and s(o)m, wherein m is 0,1 or 2 and wherein the ring system is substituted by at least one independently selected r6 group and is otpionally substituted by at least one indepenently selected ...

Benzimidazole compounds

Piperazine derivatives for the treatment of HIV infections.

EP4 receptor inhibitors to treat rheumatoid arthritis.

The invention features a method of treating rheumatoid arthritis in a mammal comprising administering an agent that inhibits prostaglandin ep4 receptor (EP4) activity. Also featured is a method of identifying agents that selectively inhibit EP4 activity in vivo.

Broadspectrum substituted benzimidazole sulfonamide HIV protease inhibitors

ANTIVIRAL DRUGS FOR TREATMENT OF ARENAVIRUS INFECTION

SUBSTITUTED PHENYLALANINE DERIVATIVES

Antiviral drugs for treatment of arenavirus infection

Aryl or heteroaryl fused imidazole compounds as anti-inflammatory and analgesic agents

Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same

Derived from benzazole, their therapeutic preparation and their uses.

Benzimidazole compounds

Ep-4 receptor inhibitors to treat rheumatoid arthritis.

Heterocyclic compunds, their preparation, compositions countaining them and method of controlling unwanted plant growth.

Aryl or heteroaryl fused imidazole compounds as anti-inflammatory and analgesic agents.

System of adjustment of the tension of an alternator.

Indanylamines acylées and their use as a medicinal product.

Method of preparation of isothiocyano-benzazoles.

Piperazine derivatives for the treatment of HIV infections.

3Ep4 receptor inhibitors to treat rheumatoid arthritis

Succinamide inhibitors of interleukin-1b convertin enzyme

COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS

Benzimidazole compounds

SUBSTITUTED PHENYLALANINE DERIVATIVES

3Ep4 receptor inhibitors to treat rheumatoid arthritis

SUBSTITUTED PHENYLALANINE DERIVATIVES

COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS

Succinamide inhibitors of interleukin-1b convertin enzyme

Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same

Piperazine derivatives for the treatment of HIV infections.

CYCLOHEXYL CONNECTIONS AS CCR5-ANTAGONISTEN

SUBSTITUTED PIPERAZINVERBINDUNGEN WHOSE USE AS FETTSUUREOXIDATIONSINHIBITOREN

INSECTICIDES ANTHRANILAMIDE

BENZIMIDAZOLDERIVATE

PYRIMIDINAMINE AS ANGIOGENIC MODULATORS

VERFAHREN ZUR HERSTELLUNG VON NEUEN 1BENZAZOLYLALKYLPIPERIDINEN UND IHREN SALZEN MIT SAEUREN

DIAMINOCYCLOHEXANUND DIAMINOCYCLOPENTANDERIVATE

N3-ALKYLIERTE OF BENZIMIDAZOL DERIVATIVES AS MEK HEMMER

VR1-BENZIMIDAZOLMODULATOREN

MONOUND BICYCLI AZOLDERIVATE THE INTERACTION OF LIGANDS WITH RISES UP RESTRAINING

REGIOSELEKTIVE, COPPER-CATALYZED SYNTHESIS OF BENZIMIDAZOLEN AND AZABENZIMIDAZOLEN

REGIOSELEKTIVE, PALLADIUM-CATALYZED SYNTHESIS OF BENZIMIDAZOLEN AND AZABENZIMIDAZOLEN

ELECTRICAL LUMINESCENCE DEVICE

BINARILY WORKING BENZIMIDAZOL DERIVATIVES AND THEIR USE AS BLOOD PRESSURE-LOWERING MEANS

BENZIMIDAZOLDERIVATE, COMPOSITIONS, THIS CONTAINING, PREPARATION OF IT AND THEIR USES

INSECTICIDES ANTHRANILAMIDE

HETERO-CYCLIC CONNECTIONS

BENZIMIDAZOLE, THESE CONNECTIONS CONTAINING DRUGS AND PROCEDURES FOR YOUR PRODUCTION

NEW ARYL ETHYL AMINE DERIVATIVES, PROCEDURES FOR YOUR PRODUCTION AND IT ABSTENTION PHARMACEUTICAL COMPOSITIONS.

IMIDAZOPYRIDINDERIVATE, PROCEDURE FOR THEIR PRODUCTION AND THEIR APPLICATION

METAL EXTRACTION PROCEDURE AND EXTRACTING AGENT FOR METALS.

N-SUBSTITUTING HETEROCYCLEN, PROCEDURE FOR YOUR PRODUCTION, AND IT CONTAINING DRUGS.

Procedure for the production of new Imidazolderivaten

N-ACYLSULFONAMID-APOPTOSIs-PROMOTER

GUANIDINOVERBINDUNGEN AS MELANOCORTIN-4-REZEPTOR (MC4-R) AGONISTEN

Procedure for the production of water-insoluble metal silicates

IMIDAZO ANNELLIERTE ISO AND HETEROCYCLEN, ANTAGONIST AS ANGIOTENSIN II

BICYCLI HETERO FLAVOUR TIC CONNECTIONS AS PROTEIN TYROSIN KINASE INHIBITORS

BENZIMIDAZOLDERIVATE

PHENYLETHANOLAMIN CONNECTIONS AND YOUR APPLICATION AS BETA3 AGONISTEN, PROCEDURES FOR YOUR PRODUCTION AND INTERMEDIATE PRODUCTS OF YOUR PRODUCTION

BENZIMIDAZOL DERIVATIVES AND YOUR USE AS CORTICOTROPIN SETTING FREE FACTOR ANTAGONIST

Procedure for the production of new Benzimidazoliumverbindungen

COMPOSITIONS AND METHODS FOR THE PREVENTION OF CELL DEATH

Nitrogen-containing organic compound, chemically amplified positive resist composition, and patterning process

An aralkylcarbamate of imidazole base is effective as the quencher. In a chemically amplified positive resist composition comprising the carbamate, deprotection reaction of carbamate takes place by reacting with the acid generated upon exposure to high-energy radiation, whereby the composition changes its basicity before and after exposure, resulting in a pattern profile with advantages including high resolution, rectangular shape, and minimized dark-bright difference.

Five-membered heterocycles useful as serine protease inhibitors

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

Azole derivatives and fused bicyclic azole derivatives as therapeutic agents

This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as modulators of the interaction between the receptor for advanced glycated end products (RAGE) and its ligands, such as advanced glycated end products (AGEs), S100/calgranulin/EN-RAGE, β-amyloid and amphoterin, and for the management, treatment, control, or as an adjunct treatment for diseases in humans caused by RAGE. Such diseases or disease states include acute and chronic inflammation, the development of diabetic late complications such as increased vascular permeability, nephropathy, atherosclerosis, and retinopathy, the development of Alzheimer's disease, erectile dysfunction, and tumor invasion and metastasis.

Material for organic electroluminescence device and organic electroluminescence device using the same

Provided are an organic electroluminescence device, which: shows high luminous efficiency; is free of any pixel defect; and has a long lifetime, and a material for an organic electroluminescence device for realizing the device. The material for an organic electroluminescence device is a compound of a specific structure having a π-conjugated heteroacene skeleton crosslinked with a carbon atom, nitrogen atom, or oxygen atom. The organic electroluminescence device has one or more organic thin film layers including a light emitting layer between a cathode and an anode, and at least one layer of the organic thin film layers contains the material for an organic electroluminescence device.

Methods of Treating a Hyperproliferative Disorder or Inhibiting Cell Growth in a Mammal

Disclosed are methods for inhibiting abnormal cell growth or treating hyperproliferative diseases in mammals, comprising administering to a mammal in heed thereof a pharmaceutical composition comprising 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide, or a pharmaceutically acceptable salt thereof, in combination with an effective amount of an anti-tumour agent or in combination with radiation therapy.

Compound for electroluminescent device and organic electroluminescent devices using the same

The present invention provides a compound of formula (I) for an organic electroluminescent device: wherein X 1 , X 2 , X 3 , Y, Ar 1 , Ar 2 , Ar 3 , Ar 4 , Ar 5 , Ar 6 , and Ar 7 are as defined in the description.

BIARYL OXYACETIC ACID COMPOUNDS

The present invention provides biaryl oxyacetic acid compounds which may be useful for treating inflammatory disorders, including disorders affecting the respiratory system and skin. The compounds provided include those of the general formula I: 2. A compound or salt according to wherein R claim 1 , R claim 1 , Rand Rare each independently selected from hydrogen and methyl.3. (canceled)4. A compound or salt according to claim 1 , wherein Ris selected from hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl and isopropyl.5. (canceled)6. A compound or salt according to claim 1 , wherein Ris selected from aryl and heteroaryl claim 1 , each optionally substituted with one to four substituents independently selected from halogen claim 1 , cyano claim 1 , (C-C) haloalkyl claim 1 , (C-C) alkoxy claim 1 , (C-C) haloalkoxy claim 1 , (C-C) alkyl claim 1 , and (C-C) alkylsulfonyl.9. A compound or salt according to claim 8 , wherein Ris selected from hydrogen claim 8 , methyl claim 8 , fluoro claim 8 , chloro claim 8 , cyano claim 8 , —CFand methoxy; and Ris selected from hydrogen claim 8 , fluoro claim 8 , chloro claim 8 , methyl claim 8 , methoxy claim 8 , cyano claim 8 , —CFand —SOCH.10. A compound or salt according to wherein Rand Rare each independently selected from fluoro claim 9 , chloro claim 9 , methoxy and hydrogen.11. (canceled)13. A compound or salt according to wherein Ris selected from naphthyl claim 6 , pyridinyl and quinolinyl claim 6 , each optionally substituted with one to four substituents independently selected from halogen claim 6 , cyano claim 6 , (C-C) haloalkyl claim 6 , (C-C) alkoxy claim 6 , (C-C) haloalkoxy claim 6 , (C-C) alkyl and alkylsulfonyl.14. A compound or salt according to claim 1 , wherein Rand Rare each hydrogen.15. A compound or salt according to claim 1 , wherein A is selected from phenyl claim 1 , pyridinyl claim 1 , benzimidazolyl claim 1 , quinolinyl claim 1 , indolyl claim 1 , pyrimidinyl and imidazopyridinyl.16. A compound ...

NOVEL HETEROCYCLIC COMPOUND, AND COMPOSITION FOR TREATING INFLAMMATORY DISEASES USING SAME

Provided are heterocyclic compounds, having effects of treating and preventing inflammatory diseases and treating skin wounds, and particularly, exhibiting effects of recovering disrupted skin barriers, mitigating inflammation, and pruritus. Also, a composition containing the compound as an effective component can be used to mitigate various inflammatory diseases and protease activated receptor-2 (PAR-2)-overexpressed diseases, and can be particularly used as a composition having an anti-inflammatory function in inflammatory skin diseases including atopic dermatitis and the like, by inhibiting PAR-2 activity. 6. A pharmaceutical composition claim 1 , comprising the heterocyclic compound or a pharmaceutically acceptable salt thereof according to and a pharmaceutically acceptable carrier.7. The pharmaceutical composition of claim 6 , which is effective in treating and preventing inflammatory skin diseases covering acne claim 6 , rosacea claim 6 , seborrheic dermatitis claim 6 , atopic dermatitis claim 6 , post-inflammatory hyperpigmentation (PIH) claim 6 , contact dermatitis claim 6 , pruritus claim 6 , psoriasis claim 6 , Lichen planus claim 6 , eczema claim 6 , skin infections claim 6 , and Netherton Syndrome.8. A method for treating skin wounds claim 1 , comprising administering an effective amount of the heterocyclic compound or a pharmaceutically acceptable salt thereof according to to a subject in need thereof.9. A method for treating and preventing metastasis of cancer claim 1 , gastrointestinal disease claim 1 , asthma claim 1 , and liver cirrhosis claim 1 , comprising administering an effective amount of the heterocyclic compound of or a pharmaceutically acceptable salt thereof according to to a subject in need thereof.10. A protease activated receptor-2 (PAR-2) inhibitor composition comprising the heterocyclic compound or a pharmaceutically acceptable salt thereof according to .11. A cosmetic composition comprising the heterocyclic compound or a ...

BENZIMIDAZOLE DERIVATIVES AS SELECTIVE BLOCKERS OF PERSISTENT SODIUM CURRENT

The present invention is directed to a compound of Formula I 2. The compound of claim 1 , wherein R is and unsubstituted straight chain or branched Calkyl.3. The compound of claim 1 , wherein R is Calkyl which is substituted with a Caryloxy group.4. The compound of claim 3 , wherein the “aryl” portion of said Caryloxy group is unsubstituted or substituted with 1-2 Calkyl or Calkoxy substitutents.5. The compound of claim 1 , wherein R is Calkyl which is substituted with a heteroaryl substitutent claim 1 , wherein said heteroaryl group is five- to six-membered ring containing 1-2 ring N atoms claim 1 , and wherein when said five- to six-membered ring containing 1-2 ring N atoms has two substituents on adjacent carbon atoms claim 1 , said substituents together with the carbon atoms to which they are attached can optionally form a phenyl ring claim 1 , and wherein said six-membered ring containing 1-2 ring N atoms claim 1 , optionally with said phenyl ring is optionally further substituted with a ring system substituent.6. The compound of claim 5 , wherein said five- to six-membered ring containing 1-2 ring N atoms claim 5 , optionally with said phenyl ring is selected from the group consisting of pyrzolyl claim 5 , imidazolyl claim 5 , pyrimidinyl claim 5 , pyrazinyl claim 5 , and benzimidazolyl.7. The compound of claim 6 , wherein said five- to six-membered ring containing 1-2 ring N atoms claim 6 , optionally with said phenyl ring is selected from the group consisting of is imidazolyl and benzimidazolyl.8. The compound of claim 1 , wherein R is Calkyl which is substituted with a —N(Calkyl)substituent.10. The compound of claim 1 , wherein Rand Rare both H.11. The compound of claim 10 , wherein m is 1 or 2.12. The compound of claim 10 , wherein m is 1 claim 10 , and X is O.13. The compound of claim 10 , wherein m is 2 claim 10 , and X is a covalent bond.14. The compound of claim 10 , wherein m is 1 claim 10 , and X is —S(═O)—.15. The compound of claim 10 , wherein m is ...

Compounds acting at multiple prostaglandin receptors giving a general anti-inflammatory response

The present invention provides a compound, that is a 1-({halo-2-[(2-hydrocarbyl or substituted hydrocarbyl)oxy]phenyl}methyl)-(fused bicyclic nitrogen heteroaryl) carboxylic acid or an ester or sulfonamide thereof. The compound may be represented by the following formula Wherein R 1 , R 2 , R 3 , R 4 A, X, W, Z and Y are as defined in the specification. The compounds may be administered to treat DP, FP, EP1, TP and/or EP4 receptor-mediated diseases or conditions.

Benzimidazole Derivatives As PI3 Kinase Inhibitors

This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer. 116.-. (canceled) This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer.The phosphoinositide 3-kinase (PI3K) pathway is among the most commonly activated in human cancer and the importance in carcinogenesis is well established (Samuels Y and Ericson K. Oncogenic PI3K and its role in cancer. 2006; 18:77-82). Initiation of signaling begins with the phosphorylation of phosphatidylinositol-4,5-bisphosphate (PIP2) to produce phosphatidylinositol-3,4,5-P3 (PIP3). PIP3 is a critical second messenger which recruits proteins ...

Benzimidazole Derivatives As PI3 Kinase Inhibitors

This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer. 1. A process for the preparation of the benzimidazole of formula (3)comprising the steps ofester hydrolyzing the methyl ester of formula (2)with lithium hydroxide in THF/water,wherein{'sub': 3', '2', '1-6, 'R2 is selected from H, —NHRa, alkoxy, halogen, —CF, —CHF, and Calkyl;'}R3 is selected from aryl and heteroaryl, wherein said aryl or heteroaryl may be substituted by one to three Rc;R4 is selected from H or Ra;{'sub': '1-6', 'each R5 is independently selected from Calkyl;'}{'sub': '1-3', 'each Ra is independently selected from Calkyl;'}{'sub': 1-3', '3, 'each Rc is independently selected from Calkyl, halogen, —CF, and hydroxy; and'}n is 0-2,or a pharmaceutically acceptable salt thereof. This application is filed as a continuation application of U.S. Ser. No. 13/251,476, filed Oct. 3, 2011, and claims priority to U.S. Provisional Application Ser. No. 61/390,314, filed Oct. 6, 2010, and U.S. Provisional Application Ser. No. 61/528,397, filed Aug. 29, 2011, both of which are incorporated herein by reference.This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), ...

PARASITICIDAL COMPOSITIONS COMPRISING BENZIMIDAZOLE DERIVATIVES, METHODS AND USES THEREOF

The invention relates to oral, topical or injectable compositions for combating liver fluke parasites in mammals, comprising at least one benzimidazole derivative active agent. The invention also provides for an improved method for eradicating and controlling liver fluke parasite infections and infestations in a mammal comprising administering the compositions of the invention to the mammal in need thereof. 2. A compound according to wherein Ris (C-C)-alkyl substituted with fluorine.3. A compound according to wherein Ris Cl.4. A compound according to wherein Ris a mono- or bi-halogen substituted phenyl ether.5. A compound according to wherein Ris a bi- or tri-halogen substituted phenyl.6. A compound according to or wherein the halogen is chlorine claim 1 , bromine or fluorine.7. A compound according to wherein Ris chlorine.8. A compound according to wherein Ris hydrogen.9. A compound according to that is 6-chloro-5-(4-chlorophenyl)-2-trifluoromethylbenzimidazole. (#130)10. A compound according to that is 6-chloro-5-(2 claim 1 ,3-dichlorophenoxy)-2-heptafluoropropylbenzimidazole. (#140)11. A compound according to that is 6-chloro-5-(3 claim 1 ,5-dichlorophenyl)-2-trifluoromethylbenzimidazole. (#247)12. A compound according to that is 6-chloro-5-(3 claim 1 ,4-dichlorophenyl)-2-trifluoromethylbenzimidazole. (#258)13. A compound according to that is 6-chloro-5-(2 claim 1 ,4-dichlorophenyl)-2-trifluoromethylbenzimidazole. (#260)14. A compound according to that is 6-chloro-5-(2 claim 1 ,3 claim 1 ,5-trichlorophenyl)-2-trifluoromethylbenzimidazole. (#261)15. A compound according to that is 5-chloro-6-(2 claim 1 ,4-dichlorophenoxy)-2-(heptafluoropropyl)-1H-1 claim 1 ,3-benzodiazole. (#273)16. A composition for treating helminth infestation comprising an anthelmintically effective amount of the compound of claim 1 , claim 1 , claim 1 , claim 1 , claim 1 , claim 1 , or and a pharmaceutically acceptable carrier.17. A composition for treating helminth infestation according to ...

Diphenyl-amine derivatives: uses, process of synthesis and pharmaceutical compositions

The invention relates to compounds of formula (I): or a pharmaceutically acceptable salt, prodrug or solvate thereof, a method of synthesis of said compounds, pharmaceutical compositions comprising them and their use as a medicament for treating inflammatory diseases.

Organic Electroluminescent Element

Disclosed is an organic electroluminescent element which is excellent with respect to luminous efficiency and driving voltage and rarely undergoes initial luminance drop. Specifically disclosed is an organic electroluminescent element which comprises, on a substrate, a pair of electrodes composed of an anode and a cathode and a light-emitting layer arranged between the electrodes, and additionally comprises at least one organic layer arranged between the light-emitting layer and the cathode, where in the light-emitting layer contains, for example, a compound (A-1), and the at least one layer arranged between the light-emitting layer and the cathode contains, for example, a compound (e-4).

Benzimidazole derivatives: preparation and pharmaceutical applications

The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to benzimidazole containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with dysregulation of histone deacetylase (HDAC).

Benzimidazole Derivatives As PI3 Kinase Inhibitors

This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kβ, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer. 1. A process for the production of the compound of formulacomprising the step ofadding iron powder to a solution of methyl 3-amino-5-(4-morpholinyl)-2-nitrobenzoate in HOAc. This application is filed as a continuation application of U.S. Ser. No. 13/876,853 filed on Mar. 29, 2013, which is filed pursuant to 35 USC 371 as a United States National Phase Application of International Patent Application Serial No. PCT/US2011/052857 filed on Sep. 23, 2011, which claims priority from 61/390,314 filed on Oct. 6, 2010 and 61/528,397 filed on Aug. 29, 2011 in the United States.This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More ...

Methods of Treating Neuropathic Pain with Benzimidazole Derivative Agonists of PPARgamma

Embodiments of the invention relate to the treatment of neuropathic pain in mammals. Embodiments of the invention include methods for treating neuropathic pain with benzimidazole derivatives with PPARgamma agonist activity, as well as methods for preparing medicaments used in such treatments of mammalian pain. 2. The method of treating neuropathic pain of claim 1 , wherein the mammal is a human.3. The method of treating neuropathic pain of claim 2 , wherein the agonist of PPARγ is 3-(2 claim 2 ,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3H-benzimidazole-5-carboxamide or a pharmaceutically acceptable salt thereof.5. The method of treating neuropathic pain of claim 4 , wherein{'sub': '27', 'Rrepresents an aryllower alkyl group whose aryl moiety may be substituted by one or two substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halo-lower alkyl group, a cyanoaryl group, an amino group, a lower alkoxy group, a nitro group, a cyano group, an aryl group, a haloaryl group, an arylsulfonyl-lower alkyl group, an arylsulfonylamino group, an aryl-lower alkyloxy group, an aryl-lower alkyl group, a heterocyclic group, an arylcarbonyl group, an arylcarbonylamino group, and an aryl-lower alkyloxy group substituted by one or two halogen atoms;'}Y represents a carbonyl group; andA represents a single bond.6. The method of treating neuropathic pain of claim 5 , wherein{'sub': '27', 'Rrepresents an aryl lower alkyl group whose aryl moiety may be substituted by one or two substituents selected from a halogen atom or an aryl group;'}{'sub': '28', 'Rrepresents a lower alkyl group or a lower cycloalkyl group;'}{'sub': '25', 'Rrepresents an alkyl group having up to 8 carbon atoms or an aryl group;'}Y represents a carbonyl group; andA represents a single bond.7. The method of treating neuropathic pain of claim 2 , wherein the agonist of PPARγ is selected from the group consisting of 6-benzenesulfonylcarbamoyl-1-(2-chlorobenzyl)-2-methylbenzimidazole ...

BENZOIMIDAZOLE-CARBOXYLIC ACID AMIDE DERIVATIVES AS APJ RECEPTOR MODULATORS

The present invention relates to benzoimidazole-carboxylic acid amide compounds of the formula I, 3. The compound of whereinR′, R″, R′″ are H;{'sup': '1', 'Ris 1-ethyl-propyl;'}{'sup': '2', 'Ris 3-thienyl;'}{'sup': '3', 'Ris H;'}{'sup': '4', 'Ris 2-methyl-propyl;'}n is 0, 1, 2;and{'sup': 9', '10, 'Z is C(O)NRR.'}4. The compound of whereinR′, R″, R′″ are H;{'sup': '1', 'Ris 1-ethyl-propyl or 2-methyl-cyclohexyl;'}{'sup': '2', 'Ris 3-thienyl;'}{'sup': '3', 'sub': 1', '2, 'Ris H, or (C-C)-alkyl;'}and{'sup': '4', 'Ris'}{'sub': 3', '5', '1', '4, 'a) (C-C)-alkyl, which may be optionally substituted by 1-3 F or S—(C-C)-alkyl,'}{'sub': 0', '1', '3', '7, 'b) (C-C)-alkylene-(C-C)-cycloalkyl, wherein said cycloalkyl is unsubstituted or mono- or di-substituted by methyl;'}or{'sup': 3', '4, 'claim-text': {'sub': 1', '4, 'are, together with the carbon atom to which they are attached, a 5- to 7-membered cycloalkyl ring, which is unsubstituted or mono-substituted by (C-C)-alkyl;'}, 'Rand R'}n is 0; and{'sub': '2', 'Z is CO—H.'}5. The compound of whereinR′, R″, R′″ are H;{'sup': '1', 'Ris 1-ethyl-propyl or 2-methyl-cyclohexyl;'}{'sup': '2', 'Ris 3-thienyl;'}{'sup': '3', 'sub': 1', '2, 'Ris H, or (C-C)-alkyl;'}and{'sup': '4', 'Ris'}{'sub': 3', '5', '1', '4, 'a) (C-C)-alkyl, which may be optionally substituted by 1-3 F or S—(C-C)-alkyl,'}{'sub': 0', '1', '3', '7, 'b) (C-C)-alkylene-(C-C)-cycloalkyl, wherein said cycloalkyl is unsubstituted or mono- or di-substituted by methyl;'}or{'sup': 3', '4, 'claim-text': {'sub': 1', '4, 'are, together with the carbon atom to which they are attached, a 5- to 7-membered cycloalkyl ring, which is unsubstituted or mono-substituted by (C-C)-alkyl;'}, 'Rand R'}{'sup': '5', 'sub': 1', '4, 'Ris H, (C-C)-alkyl or OH;'}{'sup': '6', 'sub': 1', '4, 'RH or (C-C)-alkyl;'}n is 1;and{'sub': '2', 'Z is CO—H.'}6. The compound of whereinR′, R″, R′″ are H;{'sup': '1', 'Ris 1-ethyl-propyl or 2-methyl-cyclohexyl;'}{'sup': '2', 'Ris 3-thienyl;'}{'sup': '3', 'sub': 1', ...

NOVEL COMPOUNDS AND COMPOSITIONS FOR INHIBITION OF FASN

The present invention relates to compounds and composition for inhibition of FASN, their synthesis, applications, and antidotes. An illustrative compound of the invention is shown below: 6. The compound of claim 2 , wherein A and B are 0.10. The compound of claim 2 , wherein Aris a substituted or unsubstituted 5-6 membered monocyclic aryl or heteroaryl.11. The compound of claim 10 , wherein Aris a substituted or unsubstituted 5 membered monocyclic aryl or heteroaryl and said heteroaryl has 1 or 2 heteroatoms which are independently S or N.13. The compound of claim 10 , wherein Aris a substituted or unsubstituted 6 membered monocyclic aryl or heteroaryl and said heteroaryl has 1 or 2 heteroatoms which are N.18. The compound of claim 2 , wherein Aris a substituted or unsubstituted 9 membered 6 claim 2 ,5-bicyclic heteroaryl and said heteroaryl has 1 claim 2 , 2 claim 2 , or 3 heteroatoms which are independently O claim 2 , S or N.20. The compound of claim 2 , wherein Ris a substituted or unsubstituted monocyclic or bicyclic 5-10 membered aryl or heteroaryl.21. The compound of claim 20 , wherein Ris a substituted or unsubstituted monocylic 6 membered aryl.23. The compound of claim 20 , wherein Ris a substituted or unsubstituted bicyclic 8-10 membered aryl or 8-10 membered heteroaryl.24. The compound of claim 23 , wherein Ris a substituted or unsubstituted 8 membered 5 claim 23 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 23 , 2 claim 23 , 3 claim 23 , or 4 heteroatoms and said heteroatoms are independently O claim 23 , S claim 23 , or N.26. The compound of claim 20 , wherein Ris a substituted or unsubstituted 9 membered 6 claim 20 ,5 bicyclic heteroaryl and said heteroaryl has 1 claim 20 , 2 claim 20 , 3 claim 20 , or 4 heteroatoms and said heteroatoms are independently O claim 20 , S claim 20 , or N.28. The compound of claim 20 , wherein Ris a substituted or unsubstituted 10 membered 6 claim 20 ,6 bicyclic aryl or heteroaryl and said heteroaryl has 1 claim ...

Benzimidazole Compound and Preparation Method Thereof

A benzimidazole compound and a preparation method thereof. Various substituted benzimidazoles are synthesized by a S2 reaction and a cyclization reaction. Namely, o-fluorinated aryl-N,N-dimethyl-formamidine and primary amine are subjected to an cyclization by a one-pot reaction, wherein a fluorine atom is substituted by an amino, and then dimethylamine is eliminated, thus forming the product. The method does not require the use of any metal catalyst and/or any toxic reagent, and has a specific selectivity. No isomer exists in the reaction product. 3. The method according to claim 2 , wherein a molar ratio of the compound of the formula (II) to the compound of the formula (III) is 1:1-12.4. The method according to claim 2 , wherein in Ris an electron withdrawing group.5. The method according to claim 4 , wherein Ris —NO—CFor —CN.6. (canceled)7. The method according to claim 6 , wherein the compound of the formula (III) is a fatty primary amine claim 6 , an aromatic primary amine or a primary amine containing a heterocyclic ring.8. The method according to claim 2 , wherein the solvent is N claim 2 ,N-dimethylformamide (DMF) claim 2 , dimethyl acetamide (DMA) claim 2 , dimethyl sulfoxide (DMSO) claim 2 , hexamethylphosphoramide (HMPA) claim 2 , tetrahydrofuran (THF) or dioxane.9. The method according to claim 2 , wherein a reaction temperature is 80° C.-220° C. claim 2 , and a reaction time is 0.2 h-5.0 h. This application is the national phase entry of International Application No. PCT/CN2017/103942, filed on Sep. 28, 2017, which is based upon and claims priority to Chinese Patent Application No. 201710589775.0, filed on Jul. 19, 2017, the entire contents of which are incorporated herein by reference.The present invention belongs to the technical field of organic synthesis, and relates to a benzimidazole compound and a preparation method thereof.The benzimidazole ring system is one of the most common core structures used for drug discovery, and has been found in many ...

HDAC1,2 Inhibitors

Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with HDAC1 and/or HDAC2 activity. 2. The compound of claim 1 , wherein:{'sup': '1', 'sub': '2', 'Ris selected from the group consisting of phenyl, phenyl-OH, phenyl-OSONHMe, thienyl, and furanyl;'}{'sup': '2', 'sub': 2', '1', '3, 'Ris selected from the group consisting of —H, methyl, —CH-cyclopropyl, and C-Calkyl-5-6 membered heterocycloalkyl; and'}{'sup': 3', '4, 'Rand Rare independently, at each occurrence, selected from the group consisting of —H, halo, and methyl.'}4. The compound of claim 3 , wherein:{'sup': '1', 'Ris phenyl or thienyl;'}{'sup': '2', 'sub': '2', 'Ris selected from the group consisting of absent, —H, methyl, and C-alkyl-5-6 membered heterocycloalkyl;'}{'sup': '3', 'sub': '2', 'Ris selected from the group consisting of absent, —H, and —C-alkyl-5-6 membered heterocycloalkyl; and'}{'sup': '4', 'Ris selected from the group consisting of —H, cyclopropyl, and methyl.'}7. The compound of claim 6 , wherein{'sup': '1', 'sub': '2', 'Ris —NHor —OH;'}{'sup': 2', '5, 'Ris halo or heteroaryl, wherein heteroaryl is optionally substituted by one or more R;'}{'sup': 3', '6', '6', '6', '6', '6', '5, 'sub': 1', '3', '2', '1', '3', '2', '1', '3, 'Ris independently, at each occurrence, selected from the group consisting of cycloalkyl, heterocycloalkyl, —N(R)—C-Calkyl-N(R), —O—C-Calkyl-N(R), and —N(R)—C-Calkyl-OR, wherein cycloalkyl and heterocycloalkyl are optionally substituted by one or more R;'}{'sup': '4', 'sub': 1', '6, 'Ris independently, at each occurrence, —H or C-Calkyl;'}{'sup': '5', 'sub': 1', '6, 'Ris independently, at each occurrence, —H or C-Calkyl;'}{'sup': '6', 'sub': 1', '6, 'Ris independently, at each occurrence, —H or C-Calkyl;'}and n is 1, 2, or 3.9. The compound of any one of - claim 6 , wherein Ris independently claim 6 , at each occurrence claim 6 , selected from the group ...

HETEROAROMATIC DERIVATIVES AND THEIR USE AS PHARMACEUTICALS

The invention relates to the compounds (I) and their acids and bases salts: wherein: Formula (I) the dotted line indicates a double bond; X is N or C—Rand Y is N or C—R, X and Y not being simultaneously N; A is selected from the group consisting of phenyl, naphthyl and (5-11) membered monocyclic or bicyclic unsaturated cycle or heterocycle possibly substituted as defined in the application, and A can also comprise either a further (4-7) membered heterocycle, said heterocycle being a monocycle, fused, saturated or unsaturated, the polycyclic system then comprising up to 14 members and up to 5 heteroatoms selected from N, O and S; B is selected from the group of substituents as defined in the application, or B is a 4 or (6-10) membered mono or bicyclic saturated or unsaturated heterocycle containing 1-3 heteroatoms selected from N, O and S, linked by a carbon atom, and possibly substituted as defined in the application; Ris Hydrogen or a substituent as defined in the application; Ris Hydrogen or Halogen; their preparation, their use in the antibacterial prevention and therapy, alone or in association with antibacterials, antivirulence agents or drugs reinforcing the host innate immunity, and pharmaceutical compositions and associations containing them. 2. Compounds of general formula (I) as defined in claim 1 , wherein:{'sub': 1', '1, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'X is C—R, Rbeing as defined in ;'}{'sub': 4', '5', '2', '6', '3', '12', '1', '6', '1', '6', '7', '7', '3', '12', '5', '8', '1', '6', '3', '12', 'a', 'a', '1', '6', '7', '12', '1', '6', 'a', '1', '6', 'a', 'b', 'a', 'b', '4', '5, 'B is selected from the group consisting of Halogen, CN, NRR, (C-C)Alkyl, (C-C)Cycloalkyl, O—(C-C)Alkyl, O—(C-C)Alkyl-R, O—R, O—(C-C)Cycloalkyl, O—(C-C)Cycloalkenyl, S—(C-C)Alkyl and S—(C-C)Cycloalkyl, the Alkyl and Cycloalkyl groups being possibly substituted by 1 to 3 identical or different substituents selected from OR, C(O)OR, (C-C)Alkyl, O—(C-C)Aralkyl, (C-C) ...

DEUTERATED BENZIMIDAZOLE COMPOUND AND MEDICAL USE THEREOF

The present invention relates to a medicament for treating or preventing a disease involving Na channel, for example, neuropathic pain, nociceptive pain, inflammatory pain, small-fiber neuropathy, erythromelalgia, paroxysmal extreme pain disorder, dysuria, or multiple sclerosis, comprising a compound of formula (I) wherein R, R, R, and Rare hydrogen, halogen, cyano, Calkyl, Calkoxy, etc., provided that at least one of R, R, Rand Ris the above Caryl, Caryloxy, etc., Rand Rare hydrogen, Calkyl, Ccycloalkyl, etc., Ris hydrogen, Calkyl, Ccycloalkyl, etc., m is 0, 1, or 2, L is CRR, Rand Rare hydrogen, hydroxy group, Calkyl, Calkoxy, etc., or a pharmaceutically acceptable salt thereof. 2. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1a', '1b', '1c', '1d, 'sub': 1-4', '1-4', '6-10', '6-10', '1-4', '1-4', '1-4, 'R, R, R, and Rare independently, hydrogen, halogen, cyano, Calkyl, Calkoxy (wherein the alkyl and the alkyl moiety in the alkoxy may be independently substituted with 1 to 3 the same or different halogen atoms), Caryl, Caryloxy, 5- to 12-membered heteroaryl, or 5- to 12-membered heteroaryloxy (wherein the aryl and the aryl moiety in the aryloxy, and the heteroaryl and the heteroaryl moiety in the heteroaryloxy may be independently substituted with 1 to 3 substituents selected independently from the group consisting of halogen, cyano, Calkyl optionally-substituted with 1 to 3 substituents selected independently from Substituent-group A, Calkoxy optionally-substituted with 1 to 3 substituents selected independently from Substituent-group A, and Calkylsulfonyl optionally-substituted with 1 to 3 substituents selected independently from Substituent-group A).'}3. The compound of or or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1a', '1b', '1c', '1d, 'sub': 6-10', '6-10', '1-4', '1-4, 'R, R, R, and Rare independently, hydrogen, Caryl, Caryloxy, 5- to 12-membered heteroaryl, or 5- to 12-membered ...

NOVEL COMPOUNDS AND COMPOSITIONS FOR INHIBITION OF FASN

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

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 131-. (canceled)32: A compound selected from:(a) (2R,4S)-5-Biphenyl-4-yl-2-hydroxymethyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid;(b) (2S,4S)-5-(2′-Fluorobiphenyl-4-yl)-2-hydroxymethyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid;(c) (2S,4S)-5-(3′-Fluorobiphenyl-4-yl)-2-hydroxymethyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid;(d) (2S,4S)-5-(3′-Fluorobiphenyl-4-yl)-2-hydroxymethyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid ethyl ester;(e) (2S,4S)-5-(3′-Fluorobiphenyl-4-yl)-2-hydroxymethyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 2-methoxy-ethyl ester;(f) (2S,4S)-5-(3′-Fluorobiphenyl-4-yl)-2-hydroxymethyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 2-(2-methoxy-ethoxy)-ethyl ester;(g) (2S,4S)-5-Biphenyl-4-yl-2-hydroxymethyl-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid;(h) (2S,4S)-5-(2′-Fluorobiphenyl-4-yl)-2-hydroxymethyl-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid;(i) (2S,4S)-5-(3′-Chloro-biphenyl-4-yl)-2-hydroxymethyl-4-[(1H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid;(j) (2S,4S)-5-(3′-Chloro-biphenyl-4-yl)-2-hydroxymethyl-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid;(k) (2S,4S)-5-Biphenyl-4-yl-2-hydroxymethyl-4-[(1H-[1,2,4]triazole-3-carbonyl)-amino]-pentanoic acid;(l) (S)-5-Biphenyl-4-yl-2-hydroxymethyl-4-[(2H-[1,2,4]triazole-3-carbonyl)-amino]-pentanoic acid;(m) (2S,4S)-5-Biphenyl-4-yl-2-hydroxymethyl-4-[(5-methyl-2H-[1,2,4]triazole-3-carbonyl)-amino]-pentanoic acid;(n) (2S,4S)-5-Biphenyl-4-yl-2-hydroxymethyl-4-[(5-hydroxy-2H-[1,2,4]triazole-3-carbonyl)-amino]-pentanoic acid;(o) (2S,4S)-5-Biphenyl-4-yl-2-hydroxymethyl-4-[(5-hydroxy-2H-[1,2,4]triazole-3-carbonyl)-amino]-pentanoic acid ethyl ester;(p) (2S,4S)-4-[(5-Chloro-2H-[1,2,4]triazole-3-carbonyl)-amino]-5-(2′-fluorobiphenyl-4-yl)-2-hydroxymethyl-pentanoic acid;(q) (2S,4S)-5-Biphenyl-4- ...

Novel Hydrogen Sulfate Salt

The present invention relates to Compound 1 hydrogen sulfate salt and solvates, crystalline forms and amorphous forms thereof, and to processes for their preparation.

DUAL-ACTING BENZOIMIDAZOLE ANTIHYPERTENSIVE AGENTS

The invention is directed to compounds having the formula: 2. The compound of claim 1 , wherein r is 1.5. The compound of claim 4 , wherein Ris selected from —COOH claim 4 , —SONHR claim 4 , and tetrazol-5-yl.7. The compound of claim 1 , wherein n is 0 or 1.8. The compound of claim 7 , wherein n is 1 and Ris at the 4 position of the benzoimidazole ring.9. The compound of claim 1 , wherein Ris selected from halo claim 1 , —Calkyl claim 1 , and —Calkylene-OR.10. The compound of claim 9 , wherein Ris selected from chloro claim 9 , —CH claim 9 , —CHF claim 9 , —CF claim 9 , and —CHOH.11. The compound of claim 1 , wherein Ris selected from —Calkyl and —Calkylene-O—Calkylene-R claim 1 , and Ris —Calkyl.12. The compound of claim 11 , wherein Ris —Calkyl.13. The compound of claim 1 , wherein X is —Calkylene- and one to four —CH— moieties are replaced with a —NR—C(O)— or —C(O)—NR— moiety.14. The compound of claim 13 , wherein X is selected from —C(O)NH— claim 13 , —NHC(O)— claim 13 , and —CH—NHC(O)—.15. The compound of claim 1 , wherein Ris selected from —Calkylene-SR claim 1 , —Calkylene—C(O)NRR claim 1 , —Calkylene-NR—C(O)R claim 1 , —NH—Calkylene-P(O)(OR) claim 1 , —Calkylene-P(O)ORR claim 1 , —Calkylene-CHR—COOH claim 1 , and —Calkylene—C(O)NR—CHR—COOH; Ris H; Ris —OH; Ris H; Ris H; and Ris H.21. The compound of claim 1 , wherein Ris selected from —Calkyl claim 1 , —Calkylenearyl claim 1 , and —Calkylene-Ccycloalkyl.22. The compound of claim 1 , wherein Ris H.2329-. (canceled)31. The compound of claim 30 , wherein: r is 1; Ris —COOR claim 30 , and Ris H or —Calkyl; n is 1; Ris —Calkyl; Ris —Calkyl; X is selected from —CH—NHC(O)— claim 30 , —NHC(O)— claim 30 , and —C(O)NH—; Ris selected from —Calkylene-SR claim 30 , —Calkylene—C(O)—NRR claim 30 , and —Calkylene-NR—C(O)R; Ris H or —C(O)—R; Ris —Calkyl; Ris —OH; Ris H; Ris H or —Calkyl; Ris selected from —Calkyl claim 30 , —Calkylenearyl claim 30 , and —Calkylene-Ccycloalkyl; Ris H; the alkyl in Ris optionally substituted ...

BUMETANIDE DERIVATIVES FOR THE THERAPY OF HYPERHIDROSIS

The present invention relates to bumetanide derivatives of formula (I) as well as pharmaceutical compositions comprising these compounds for use in the treatment or prevention of diseases/disorders involving Na—K2Cl-cotransporters (NKCCs), and particularly for use in the treatment or prevention of hyperhidrosis. 3. The compound for use according to claim 2 , wherein Ris —COO—(Calkyl) claim 2 , wherein the alkyl moiety of said —COO—(Calkyl) is optionally substituted with one or more groups independently selected from halogen claim 2 , —CF claim 2 , —CN claim 2 , —NO claim 2 , —NH claim 2 , —NH(Calkyl) claim 2 , —N(Calkyl)(Calkyl) claim 2 , —OH claim 2 , —O(Calkyl) claim 2 , —SH and —S(Calkyl) claim 2 , and further wherein one or two —CH— units comprised in the alkyl moiety of said —COO—(Calkyl) are each optionally replaced by a group independently selected from —O— claim 2 , —CO— claim 2 , —COO— claim 2 , —O—CO— claim 2 , —NH— claim 2 , —N(Calkyl)- claim 2 , —NH—CO— claim 2 , —N(Calkyl)-CO— claim 2 , —CO—NH— claim 2 , —CO—N(Calkyl)- claim 2 , —S— claim 2 , —SO— claim 2 , —SO— claim 2 , —SO—NH— claim 2 , —SO—N(Calkyl)- claim 2 , —NH—SO— and —N(Calkyl)-SO—.4. The compound for use according to or claim 2 , wherein Ris —COO—CH.5. The compound for use according to claim 2 , wherein Ris —COOH.6. The compound for use according to claim 2 , wherein Ris selected from —(Calkylene)-NH—(Calkylene)-R claim 2 , —COO—(Calkylene)-R claim 2 , —O—CO—(Calkylene)-R claim 2 , —CO—(Calkylene)-R claim 2 , —CO—NH—(Calkylene)-R claim 2 , —CO—N(Calkyl)-(Calkylene)-R claim 2 , —NH—CO—(Calkylene)-Rand —N(Calkyl)-CO—(Calkylene)-R claim 2 , wherein Ris independently selected from —CF claim 2 , —CN and halogen.7. The compound for use according to or claim 2 , wherein Ris —(Calkylene)-NH—(Calkylene)-CF.8. The compound for use according to any one of to claim 2 , wherein Ris hydrogen.9. The compound for use according to any one of to claim 2 , wherein Ris selected from —SO—NH claim 2 , —SO—NH(Calkyl ...

COMPOUNDS USEFUL AS INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND/OR TRYPTOPHAN DIOXYGENASE

The present invention relates to bicyclic compounds and compositions and methods which may be useful as inhibitors of IDO1, IDO2, and TDO for the treatment or prevention of diseases such as cancer. 2. The compound as recited in claim 1 , wherein Lis L-Rand Lis H.3. The compound as recited in claim 2 , wherein Ris Rand Ris H.4. The compound as recited in claim 2 , wherein Ris H and Ris R.5. The compound as recited in claim 1 , or a salt or tautomer thereof claim 1 , wherein{'sup': 1', '5, 'Lis chosen from a bond, —O— and —N(R)—;'}{'sup': '2', 'Lis chosen from —C(O)NH— and NHC(O)—;'}{'sup': 1', '7, 'Ris aryl or heteroaryl, and is optionally substituted with one or more Rgroups;'}{'sup': 2', '8, 'Ris H or is chosen from alkyl, cycloalkyl, and heterocycloalkyl, any of which is optionally substituted with one or more Rgroups;'}{'sup': 3', '9, 'Ris H or is chosen from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (aryl)aryl, (aryl)heteroaryl, (heteroaryl)aryl, (heteroaryl)heteroaryl, aryl(cycloalkyl), and heteroaryl(cycloalkyl), any of which is optionally substituted with one or more Rgroups;'}{'sup': 4', '10, 'Ris H or is chosen from alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, any one of which is optionally substituted with one or more Rgroups;'}{'sup': 3', '4', '10, 'or Rand R, together with the intervening atoms, form a first heteroaryl ring, which is optionally fused with a second aryl or heteroaryl ring to form a bicyclic heteroaryl system, said first heteroaryl ring or bicyclic heteroaryl system is optionally substituted with one or more Rgroups;'}{'sup': '5', 'Ris H or is chosen from alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and'}{'sup': 7', '8', '9', '10, 'sub': '3-6', 'each R, R, R, and Ris independently chosen from alkyl, Ccycloalkyl, halo, hydroxy, alkoxy, and cyano.'}7. The compound as recited in claim 6 , or a salt or tautomer thereof claim 6 , wherein{'sup': 1', '5, 'Lis chosen from a bond, —O—, and —N(R)—;'}{'sup': 1 ...

Organic electroluminescent device

An organic electroluminescent device having high luminous efficiency, low driving voltage, and particularly a long lifetime is provided by combining various materials for an organic electroluminescent device, which have excellent hole and electron injection/transport performances, electron blocking ability, stability in a thin-film state, and durability as materials for an organic electroluminescent device having high luminous efficiency and high durability so as to allow the respective materials to effectively reveal their characteristics. In the organic electroluminescent device having at least an anode, a hole transport layer, a light emitting layer, an electron transport layer and a cathode in this order, the hole transport layer includes an arylamine compound represented by the following general formula (1), and the light emitting layer includes an amine derivative of the following general formula (2) having a condensed ring structure.

HYDROXIDE-CATALYZED FORMATION OF SILICON-OXYGEN BONDS BY DEHYDROGENATIVE COUPLING OF HYDROSILANES AND ALCOHOLS

The present disclosure is directed to methods for dehydrogenatively coupled hydrosilanes and alcohols, the methods comprising contacting an organic substrate having at least one organic alcohol moiety with a mixture of at least one hydrosilane and sodium and/or potassium hydroxide, the contacting resulting in the formation of a dehydrogenatively coupled silyl ether. The disclosure further described associated compositions and methods of using the formed products. 1. A method comprising contacting an organic substrate having at least one alcohol moiety with a mixture of at least one hydrosilane and sodium and/or potassium hydroxide , the contacting resulting in the formation of a dehydrogenatively coupled silyl ether , wherein the contacting is done in the absence of a crown ether.2. The method of claim 1 , wherein the hydrosilane has a structure of Formula (I) or of Formula (II):{'br': None, 'sub': 3−m', 'm+1, '(R)Si(H)\u2003\u2003(I)'}{'br': None, 'sub': 2−m', 'm+1', '3−m', 'm, '(R)(H)Si—Si(R)(H)\u2003\u2003(II)'}{'sub': 1-24', '2-24', '2-24', '1-24', '1', '20', '5', '20', '1', '20', '5', '20', '1', '20', '1', '20', '5', '20', '2', '20', '5', '20', '1', '20, 'where: m is independently 0, 1, or 2; and each R is independently optionally substituted Calkyl or heteroalkyl, optionally substituted Calkenyl or heteroalkenyl, optionally substituted Calkynyl or heteroalkynyl, optionally substituted 6 to 18 ring membered aryl or 5 to 18 ring membered heteroaryl, optionally substituted 6 to 18 ring-membered alkaryl or 5 to 18 ring-membered heteroalkaryl, optionally substituted 6 to 18 ring-membered aralkyl or 5 to 18 ring-membered heteroaralkyl, optionally substituted —O—Calkyl or heteroalkyl, optionally substituted 6 to 18 ring-membered aryloxy or 5 to 18 ring-membered heteroaryloxy, optionally substituted 6 to 18 ring-membered alkaryloxy or 5 to 18 ring-membered heteroalkaryloxy, or optionally substituted 6 to 18 ring-membered aralkoxy or 5 to 18 ring-membered ...

DETERMINATION OF AQUEOUS NITRATE CONCENTRATION

A method of measuring nitrate concentration in an aqueous sample includes mixing the aqueous sample with a water-soluble thioether chosen to reduce nitrate in the aqueous sample to nitrite in the presence of a water soluble catalyst, and a water soluble reagent system adapted to interact with nitrite to generate a color; measuring color generation, and correlating the color generation to nitrate concentration. 1. A method of measuring nitrate concentration in an aqueous sample , comprisinga. mixing the aqueous sample with a water-soluble thioether chosen to reduce nitrate in the aqueous sample to nitrite in the presence of a water soluble catalyst, and a water soluble reagent system adapted to interact with nitrite to generate a color,b. measuring color generation, andc. correlating the color generation to nitrate concentration.2. The method of wherein the water soluble thioether comprises a thioether-containing a five-membered claim 1 , aromatic heterocyclic compound claim 1 , a phenylalkyl thioether or a substituted phenylalkyl thioether.4. The method of wherein the hydrophilic polymer is a polyalkyleneoxide.5. The method of wherein at least one of R claim 3 , R claim 3 , R claim 3 , R claim 3 , and Ris —ORwherein Ris selected from the group consisting of H claim 3 , a C-Calkyl group claim 3 , a C-Csulfonate terminated alkyl group claim 3 , a phenyl group claim 3 , and a polyalkylene oxide group claim 3 , —NRRwherein RE and Rare selected independently from the group consisting of H claim 3 , a C-Calkyl group claim 3 , a C-Csulfonate terminated alkyl group claim 3 , and a polyalkylene oxide group claim 3 , a dihydroxybenzene group claim 3 , a phenyl diamine group claim 3 , a phenyl diether group claim 3 , a carboxy late group claim 3 , and a polyalkyleneoxide group; or Rand Rtogether form a chain of four or five members selected from the group of CH claim 3 , CH claim 3 , NH claim 3 , CC(O)OH or NR claim 3 , wherein Ris an C-Calkyl group or C-Csulfonate terminated ...

Imaging histone deacetylases with a radiotracer using positron emission tomography

wherein R1 is a moiety including a positron emitter; R2 represents hydrogen, or substituted or unsubstituted alkyl, or substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and n is an integer selected from 0 or 1. In one version of the compound of formula (I), R1 is a moiety including an adamantyl group.

Organic Material for an Electronic Optoelectronic Device and Electronic Device Comprising the Organic Material

The present invention relates to an organic material and to an electronic device comprising the organic material, particularly to an electroluminescent device, particularly to an organic light emitting diode (OLED), wherein the semiconducting material comprises a multiple-substituted phenyl moiety, an aryl moiety with at least two fused rings, a polar moiety and optional linkers between these moieties. 2. The compound of claim 1 , wherein the compound has a dipole moment of about ≥0.6 Debye.3. The compound of claim 1 , wherein R is chosen so that the dipole moment of the compound R-phenyl is about ≥0.6 Debye.6. The compound of any of claim 1 ,wherein 1≤a+b+c+d+e≤4.7. The compound of claim 1 ,wherein 2≤a+b+c+d+e≤3.8. The compound of claim 1 ,{'sub': 2', '30, 'wherein R is selected from substituted or unsubstituted Cto Cheteroaryl group and CN'}10. The compound of claim 1 ,wherein n is 1 or 2.11. An electronic device comprising a first electrode claim 1 , a second electrode claim 1 , and arranged between the first and second electrode claim 1 , a layer comprising a compound according to .12. The electronic device of claim 1 , wherein the electronic device comprises a hole blocking layer comprising a compound according to .13. The electronic device of claim 1 , wherein the electronic device comprises an electron transport layer comprising a compound according to .14. The electronic device according to claim 11 , wherein the electronic device is an electroluminescent device.15. The electronic device according to claim 11 , wherein the electronic device is an organic light emitting diode.16. A display device comprising an electronic device according to .17. A display device according to claim 11 , wherein the display device comprises an organic light emitting diode according to . The present invention relates to an organic material and to an electronic device comprising the organic material, particularly to an electroluminescent device, particularly to an organic light ...

METHODS OF TREATING A FLAVIVIRIDAE FAMILY VIRAL INFECTION, COMPOSITIONS FOR TREATING A FLAVIVIRIDAE FAMILY VIRAL INFECTION, AND SCREENING ASSAYS FOR IDENTIFYING COMPOSITIONS FOR TREATING A FLAVIVIRIDAE FAMILY VIRAL INFECTION

Briefly described, embodiments of this disclosure include compositions, pharmaceutical compositions, methods of treating a host infected with a virus from the Flaviviridae family of viruses, methods of identifying a candidate agent for the treatment of hepatitis C virus (HCV) infection, and the like. 1. A method of treating a host infected with a virus from the Flaviviridae family of viruses , the method comprising administering to the host a therapeutically effective amount of an inhibiting agent to reduce the viral load in the host.2. The method of claim 1 , wherein the Flaviviridae family of viruses includes viruses selected from the group consisting of: a flavivirus claim 1 , a pestivirus claim 1 , a Hepatitis C virus claim 1 , a yellow fever virus (YFV); a Dengue virus; a Japanese Encephalitis virus; a Murray Valley Encephalitis virus; a St. Louis Encephalitis virus; a West Nile virus; a tick-borne encephalitis virus; a Hepatitis C virus; a Kunjin virus; a Central European encephalitis virus; a Russian spring-summer encephalitis virus; a Powassan virus; a Kyasanur Forest disease virus; and a Omsk hemorrhagic fever virus.3. The method of claim 1 , wherein the virus is Hepatitis C virus.4. The method of claim 1 , wherein the inhibiting agent is selected from the group consisting of: clemizole claim 1 , a clemizole analog claim 1 , and a compound having a clemizole scaffold; an H1 antagonist claim 1 , an H1 receptor antagonist that share structural similarity with clemizole; cinoxacin claim 1 , a cinoxacin analog claim 1 , and a compound having a cinoxacin scaffold; norepinephrine claim 1 , a norepinephrine analog claim 1 , and a compound having a norepinephrine scaffold; glybenclamide claim 1 , a glybenclamide analog claim 1 , and a compound having a glybenclamide scaffold; spiradoline claim 1 , a spiradoline analog claim 1 , and a compound having a spiradoline scaffold; tropicamide claim 1 , a tropicamide analog claim 1 , and a compound having a tropicamide ...

Heterocyclic Derivative and Pharmaceutical Drug

The present invention provides a novel heterocyclic derivative or a pharmaceutically acceptable salt thereof. For example, the present invention provides a heterocyclic derivative of the general formula [1] or its tautomer, or a pharmaceutically acceptable salt thereof: 2. The compound according to claim 1 , wherein the ring A is a group of formula [4] and Xis NH.3. The compound according to claim 1 , wherein Ris phenyl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthalen-5-yl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthalen-6-yl claim 1 , 2 claim 1 ,3-dihydro-1H-inden-4-yl claim 1 , 2 claim 1 ,3-dihydro-1H-inden-5-yl claim 1 , 1 claim 1 ,2-dihydrocyclobutabenzen-3-yl claim 1 , or 1 claim 1 ,2-dihydrocyclobutabenzen-4-yl claim 1 , and said phenyl is optionally substituted with one to three groups selected from the group consisting ofi) halogen,ii) alkyl optionally substituted with one to three halogens,iii) alkoxy, andiv) cyano.4. The compound according to claim 1 , wherein Ris phenyl and said phenyl is optionally substituted with one to three groups selected from the group consisting ofi) halogen,ii) alkylsulfonyl,iii) alkoxy optionally substituted with alkoxy,iv) alkynyl optionally substituted with alkoxyalkyl or cycloalkyl, andv) alkyl optionally substituted with one to three groups selected from the group consisting of halogen, alkoxy, alkoxyalkoxy, cycloalkyl and phenyl.5. The compound according to claim 1 , whereinthe ring A is a group of formula [4],{'sup': '1', 'Xis NH,'}{'sup': '2', 'claim-text': i) hydrogen,', 'ii) alkyl optionally substituted with a group selected from the group consisting of halogen, monoalkylamino, dialkylamino, monoalkylaminocarbonyl, dialkylaminocarbonyl, a saturated cyclic aminocarbonyl, alkoxy, alkoxyalkoxy and alkylcarbonyloxy,', 'iii) cycloalkyl optionally substituted with alkyl optionally substituted with one to three halogens,', 'iv) alkoxy,', 'v) a saturated heterocyclic group optionally ...

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 ...

NOVEL COMPOUNDS AND COMPOSITIONS FOR INHIBITION OF FASN

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

Organometallic compound and organic light-emitting device including same

Provided are an organometallic compound represented by Formula 1 and an organic light-emitting device including the organometallic compound. The organic light-emitting device includes; a first electrode; a second electrode facing the first electrode; an organic layer between the first electrode and the second electrode and comprising an emission layer; and at least one of the organometallic compound represented by Formula 1.

NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS

The present invention discloses compounds according to Formula I: 2. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris Me.6. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris H claim 1 , F claim 1 , or Cl.7. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris H claim 1 , Me claim 1 , or Et.8. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris CN claim 1 , F claim 1 , Cl claim 1 , —SOMe or —SOEt.10. A compound claim 1 , or pharmaceutically acceptable salt thereof claim 1 , according to wherein the compound is (1R claim 1 ,2R)—N-[6-[(6-cyano-4-methyl-3-pyridyl)oxy]-1-methyl-benzimidazol-4-yl]-2-fluoro-cyclopropanecarboxamide.11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , according to .12. The pharmaceutical composition according to comprising a further therapeutic agent.13. (canceled)14. A method for the treatment claim 1 , prevention or prophylaxis of allergic diseases claim 1 , inflammatory diseases claim 1 , autoimmune diseases claim 1 , proliferative diseases claim 1 , transplantation rejection claim 1 , diseases involving impairment of cartilage turnover claim 1 , congenital cartilage malformations claim 1 , and/or diseases associated with hypersecretion of IL6 or hypersecretion of interferons claim 1 , said method comprising administering an amount of a compound according to claim 1 , sufficient to effect said treatment claim 1 , prevention or prophylaxis.15. The pharmaceutical composition according to claim 12 , wherein the further therapeutic agent is an agent for the treatment of allergic diseases claim 12 , inflammatory diseases claim 12 , autoimmune diseases claim 12 , proliferative diseases claim 12 , transplantation rejection claim 12 , diseases involving impairment of cartilage ...

2-ARYLBENZIMIDAZOLES AS PPARGC1A ACTIVATORS FOR TREATING NEURODEGENERATIVE DISEASES

The compound 2-(4-tert-Butylphenyl)-1H-benzo[d]imidazol-5-ol: 2. A compound according to claim 1 , in free base form.3. A compound according to claim 1 , in the form of a pharmaceutically acceptable salt.4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to .5. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to . This application is a continuation of U.S. application Ser. No. 16/888,040, filed May 29, 2020, which is a continuation under 35 USC § 111(a) of PCT/US2019/045229, filed Aug. 6, 2019. PCT/US2019/045229 claimed priority from U.S. Provisional application 62/714,962, which was filed Aug. 6, 2018. The contents of each of these applications are incorporated herein by reference in their entirety.The invention relates to the use of 2-arylbenzimidazole, 2-arylbenzoxazole, 2-arylbenzothiazole, 2-arylimidazo[1,2-a]pyridine, and prodrug derivatives thereof as chemical activators of Ppargc1a to treat neurodegenerative diseases.Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that is characterized by the loss of motor neurons, leading to progressive decline in motor function and ultimately death. The motor symptoms of ALS include muscle weakness, twitching and wasting, which leads to difficulties in speaking, swallowing and breathing. The cause of motor neuron death in ALS is unknown and 5-10% of the ALS cases are inherited.Activation of immune cells in the central as well as peripheral nervous system has been suggested to be a critical determinant of disease progression in ALS (Phani et al, Front Pharmacol. 3:150, 2012). Specifically, microglia and macrophages have been shown to play distinct roles in the orchestration of neuroinflammation in this disease (Dibaj et al, PLoS One. 6(3):e17910, 2011; Boillee et al, Science, 312:1389-92, 2006). Of note, bone marrow transplantation (BMT) to replace host myeloid cells has been shown to ...

Benzimidazole Derivatives As PI3 Kinase Inhibitors

This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer.

Compounds which have a protective activity with respect to the action of toxins and of viruses with an intracellular mode of action

The subject matter of the present invention is novel families of compounds which are aromatic amine, imine, aminoadamantane and benzodiazepine derivatives, medicaments comprising same and the use thereof as inhibitors of the toxic effects of toxins with intracellular activity, such as, for example, ricin, and of viruses that use the internalization pathway for infecting cells.

Prostaglandin Receptor EP2 Antagonists, Derivatives, Compositions, and Uses Related Thereto

The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, neuroinflammation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof. 2. The composition of claim 1 , wherein n is 2 and Ris phenyl substituted with one or more halogen claim 1 , alkyl claim 1 , or alkoxy.3. The composition of claim 1 , wherein U is CX claim 1 , wherein Xis alkyl substituted with one or more halogen.4. The composition of claim 1 , wherein W is CXand Xis hydrogen.5. A compound of Formula IB as in claim 1 , selected from the group consisting of:N-(2-(2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,3-(3,4-dimethoxyphenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,N-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,3-(3,4-dimethoxyphenyl)-N-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)ethyl)acrylamide,3-(benzo[d][1,3]dioxol-5-yl)-N-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)ethyl)acrylamide,N-(2-(1H-benzo[d]imidazol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,3-(3,4-dimethoxyphenyl)-N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)acrylamide,N-(2-(5-fluoro-2-(trifluoromethyl)-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,3-(3,4-dimethoxyphenyl)-N-(2-(5-fluoro-2-(trifluoromethyl)-1H-indol-1-yl)ethyl)acrylamide,N-(3-(2-methyl-1H-indol-1-yl)propyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,N-methyl-N-(2-(2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,N-(2 ...

Compounds for treating respiratory disease

Compounds of general formula (I) and their tautomeric forms all enantiomers and isotopic variants and salts and solvates thereof:whereinrepresents a single or a double bond and R1, R2, X1, X2, X3, X4, X5, Y and Z are as defined herein;are useful for treating respiratory disease and other diseases and conditions modulated by TMEM16A.

POLYCYCLIC COMPOUND AND ORGANIC LIGHT EMITTING DEVICE INCLUDING THE SAME

The present specification provides a polycyclic compound and an organic light emitting device including the same. 4. The compound of claim 3 , wherein Ain Chemical Formula 3 is hydrogen; a nitrile group; a substituted or unsubstituted pyridyl group; or a substituted or unsubstituted benzimidazole group; and Ais hydrogen; a nitrile group; a substituted or unsubstituted pyridyl group; a substituted or unsubstituted benzimidazole group; or a substituted or unsubstituted benzoimidazophenanthridine group.10. An organic light emitting device comprising:a first electrode;a second electrode provided opposite to the first electrode; andone or more organic material layers provided between the first electrode and the second electrode,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein one or more layers of the organic material layers include the compound of .'}11. The organic light emitting device of claim 10 , wherein the organic material layer including the compound is an electron transfer layer. This application claims priority to and the benefits of Korean Patent Application No. 10-2014-0127112, filed with the Korean Intellectual Property Office on Sep. 23, 2014, the entire contents of which are incorporated herein by reference.The present specification relates to a polycyclic compound and an organic light emitting device including the same.An organic light emission phenomenon generally refers to a phenomenon converting electrical energy to light energy using an organic material. An organic light emitting device using an organic light emission phenomenon normally has a structure including an anode, a cathode, and an organic material layer therebetween. Herein, the organic material layer is often formed in a multilayer structure formed with different materials in order to increase efficiency and stability of the organic light emitting device, and for example, may be formed with a hole injection layer, a hole transfer layer, a light emitting layer, an electron ...

CRYSTALLINE POLYMORPHS OF PRACINOSTAT AND PRACINOSTAT SALTS

The present disclosure encompasses crystalline polymorphs of Pracinostat and of Pracinostat salts, and pharmaceutical compositions thereof. 1. A crystalline polymorph of Pracinostat , designated Form P3 , characterized by data selected from one or more of the following:{'figref': {'@idref': 'DRAWINGS', 'FIG. 3'}, 'a) an X-ray powder diffraction pattern substantially as depicted in ;'}b) an X-ray powder diffraction pattern having peaks at 5.7, 8.4, 10.2, 14.3 and 15.3 degrees 2-theta±0.2 degrees 2-theta;{'sup': '13', 'figref': {'@idref': 'DRAWINGS', 'i': a', 'b, 'FIGS. 14, 14'}, 'b': '14', 'i': 'c;', 'c) a solid state C NMR spectrum substantially as depicted in any one of and'}{'sup': '13', 'd) a solid state C NMR spectrum having peaks at the range of 100-200 ppm at 157.29, 141.28, 137.17, 130.06 and 120.57 ppm±2 ppm;'}{'sup': '13', 'e) a solid state C NMR spectrum having the following chemical shift absolute differences from a peak at 165.62 ppm±2 ppm of 8.33, 24.34, 28.45, 35.56 and 45.05±2 ppm;'}{'sup': '13', 'f) a solid state C NMR spectrum having chemical shift difference from a peak at 165.62 ppm±1 ppm to 130.06 ppm±1 ppm of 35.36 ppm±1 ppm;'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 17'}, 'g) a FTIR spectrum substantially as depicted in ; and'}h) combinations of these data.2. The crystalline polymorph of Pracinostat according to claim 1 , characterized by an X-ray powder diffraction pattern having peaks at 5.7 claim 1 , 8.4 claim 1 , 10.2 claim 1 , 14.3 and 15.3 degrees 2-theta±0.2 degrees 2-theta claim 1 , and also having any one claim 1 , two claim 1 , three claim 1 , four or five additional peaks selected from the group consisting of 16.5 claim 1 , 17.8 claim 1 , 20.1 claim 1 , 20.9 and 23.3 degrees 2-theta±0.2 degrees 2-theta.3. The crystalline polymorph of Pracinostat according to claim 1 , wherein the crystalline form is anhydrous.4. A crystalline polymorph of Pracinostat claim 1 , designated Form P7 claim 1 , characterized by data selected from one or ...

PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS

The present application provides the compounds of formula I 11. A pharmaceutical composition comprising the compound of and at least one pharmaceutically acceptable vehicle.12. A method of treating a disease or condition in a human in need thereof comprising administering to the human a therapeutically effective amount of the compound of claim 1 , wherein the disease or condition is selected from cancer claim 1 , hematologic malignancies claim 1 , leukemias claim 1 , lymphomas claim 1 , myeloproliferative disorders claim 1 , myelodysplastic syndromes claim 1 , plasma cell neoplasms claim 1 , or solid tumor.13. A method of treating a disease or condition in a human in need thereof comprising administering to the human a therapeutically effective amount of the compound of claim 1 , wherein the disease or condition is selected from inflammation claim 1 , fibrosis claim 1 , autoimmune disorders claim 1 , allergic conditions claim 1 , hypersensitivity claim 1 , cardiovascular diseases claim 1 , neurodegenerative diseases claim 1 , renal disorders claim 1 , viral infections claim 1 , obesity claim 1 , and autoimmune diseases.14. A method of treating prostate cancer in a human in need thereof comprising administering to the human a therapeutically effective amount of the compound of .15. A method of inhibiting the activity of phosphatidylinositol 3-kinase polypeptide by contacting the polypeptide with the compound of .16. A method of inhibiting excessive or destructive immune reactions or growth or a proliferation of cancer cells claim 1 , comprising administering an effective amount of the compound of .17. A method of treating a disease or condition in a human in need thereof comprising administering to the human a therapeutically effective amount of the compound of in combination with therapeutically effective amount of a compound that inhibits or modulates the activity of poly(ADP-ribose) polymerases (PARP) claim 1 , Tankyrases (TANKs) claim 1 , matrix ...

BICYCLIC ACETYL-COA CARBOXYLASE INHIBITORS AND USES THEREOF

The present invention provides compounds of formula (I); 3. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Xis —NR—.4. The compound according to claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Ris hydrogen.5. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris Calkyl claim 2 , benzyl claim 2 , or pyrazinylmethyl claim 2 , wherein Ris optionally substituted on one or more carbon atom with one or more R; and wherein when Ris pyrazinyl claim 2 , the hydrogen of the{'sub': '1-7', '—NH— group may be independently optionally replaced with a Calkyl.'}6. The compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein R claim 5 , for each occurrence claim 5 , is independently halo claim 5 , Calkyl claim 5 , wherein Rmay be optionally substituted on one or more carbon atoms with one or more independently selected R.7. The compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein R claim 6 , for each occurrence claim 6 , is independently halo claim 6 , hydroxy claim 6 , carboxy claim 6 , Calkoxycarbonyl claim 6 , Calkanoyloxy claim 6 , 2-amino-3-phenyl-propanoyloxy claim 6 , 2-amino-3-methyl-butanoyloxy claim 6 , phosphonooxy claim 6 , or di-(Calkoxy)phosphoryloxy.8. The compound according to claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Rand Rtogether with the nitrogen atom to which they are attached form a 3- to 7-membered heterocyclyl claim 3 , wherein the heterocyclyl may be optionally substituted on one or more carbon atoms with one or more R; and wherein when the heterocyclyl comprises one or more —NH— claim 3 , the hydrogen of each —NH— group may be independently optionally replaced with R.9. The compound according to claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein Rand Rtogether with the nitrogen atom to which they ...

CHEMOSELECTIVE METHYLENE HYDROXYLATION IN AROMATIC MOLECULES

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

Hydrazide compound and kinase inhibitor

The present invention aims to provide a novel compound capable of promoting cell proliferation in a cell culture (particularly three-dimensional cell culture). The hydrazide compound represented by the formula (I); wherein each symbol is as defined in DESCRIPTION, or a salt thereof, and a composition containing same can remarkably promote cell proliferation, sphere formation, cyst formation and/or organoid formation, and can also remarkably inhibit the activities of kinase such as LATS1, LATS2 and the like.

PROSTAGLANDIN RECEPTOR EP2 ANTAGONISTS, DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO

The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, neuroinflammation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof. 2. The composition of claim 1 , wherein n is 2 and Ris phenyl substituted with one or more halogen claim 1 , alkyl claim 1 , or alkoxy.3. The composition of claim 1 , wherein U is CX claim 1 , wherein Xis alkyl substituted with one or more halogen.4. The composition of claim 1 , wherein W is CXand Xis hydrogen.5. A compound of Formula IB as in claim 1 , selected from the group consisting of:N-(2-(2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,3-(3,4-dimethoxyphenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,N-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,3-(3,4-dimethoxyphenyl)-N-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)ethyl)acrylamide,3-(benzo[d][1,3]dioxol-5-yl)-N-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)ethyl)acrylamide,N-(2-(1H-benzo[d]imidazol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,3-(3,4-dimethoxyphenyl)-N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)acrylamide,N-(2-(5-fluoro-2-(trifluoromethyl)-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,3-(3,4-dimethoxyphenyl)-N-(2-(5-fluoro-2-(trifluoromethyl)-1H-indol-1-yl)ethyl)acrylamide,N-(3-(2-methyl-1H-indol-1-yl)propyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,N-methyl-N-(2-(2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,N-(2 ...

ORGANIC ELECTRONIC MATERIAL AND ORGANIC ELECTROLUMINESCENT DEVICE

An organic light-emitting material having the structure of formula (I) or (II) as described below and an organic light-emitting device (OLED) are disclosed. The OLED adopts the compound containing fluoranthene group as the electron transport material possessing good electron transport and injection ability. The material also enhances the luminous efficiency and lifetime of the device because of its excellent thermal stability and film-forming properties. At the same time, the high triplet energy and excellent electron transport capacity of the material containing fluoranthene group make it suitable to be used as the host for phosphorescent devices, increasing the number of electrons in the light-emitting layer and the efficiency of the device. 2. The organic electronic material according to claim 1 , wherein any four of R-Rare hydrogen and the other is five-membered or six-membered heteroaromatic ring substituted with fluorenyl or alkyl or phenyl or naphthyl claim 1 , diphenyl amino claim 1 , phenyl-naphthylamine claim 1 , triphenylsilyl claim 1 , diphenyl phosphine oxide claim 1 , phenyl carbonyl or phenyl sulfonyl.3. The organic electronic material according to claim 2 , wherein the said five-membered or six-membered heteroaromatic ring is carbazolyl claim 2 , pyrimidinyl claim 2 , pyridyl claim 2 , thiazolyl claim 2 , triazole group or triazine group.4. The organic electronic material according to claim 2 , wherein the said fluorenyl is 9 claim 2 ,9-dimethyl-fluorenyl claim 2 , 9 claim 2 ,9-diphenyl fluorenyl claim 2 , 9 claim 2 ,9-di-p-tolyl-9H-fluorenyl or spiro fluorenyl.5. The organic electronic material according to claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , Rare hydrogen.6. An organic light-emitting material according to claim 1 , wherein A is C(R) claim 1 , N(R) claim 1 , S claim 1 , O claim 1 , S(O); R claim 1 , Rindependently represent hydrogen claim 1 , methyl claim 1 , phenyl claim 1 , or methyl phenyl claim 1 , or five-membered cyclic ...

NOVEL BENZIMIDAZOLE COMPOUND AND MEDICAL USE THEREOF

The present invention provides a medicament for treating a disease involving Nav 1.7 such as neuropathic pain, nociceptive pain, inflammatory pain, small-fiber neuropathy, erythromelalgia, paroxysmal extreme pain disorder, dysuria, and multiple sclerosis, which comprises a compound of formula (I): 1. A compound selected from the group of compounds consisting of:a) 1-[6-(4-fluorophenoxy)-1H-benzimidazol-1-yl]-2-methylpropan-2-ol;b) 1-[6-(4-chlorophenoxy)-1H-benzimidazol-1-yl]-2-methylpropan-2-ol;c) 2-methyl-1-(6-{[5-(trifluoromethyl)pyridin-2-yl]oxy}-1H-benzimidazol-1-yl)propan-2-ol;d) 2-methyl-4-(6-{[5-(trifluoromethyl)pyridin-2-yl]oxy}-1H-benzimidazol-1-yl)butan-2-ol;e) 3-({6-[4-(trifluoromethoxy)phenoxy]-1H-benzimidazol-1-yl}methyl)oxetan-3-ol;f) 4-[6-(4-chlorophenoxy)-1H-benzimidazol-1-yl]-2-methylbutan-2-ol;g) cis-4-(6-{[5-(trifluoromethyl)pyridin-2-yl]oxy}-1H-benzimidazol-1-yl)cyclohexanol;h) 3-({6-[2-methoxy-4-(trifluoromethyl)phenyl]-1H-benzimidazol-1-yl}methyl)oxetan-3-ol;i) 3-({5-[2-methoxy-4-(trifluoromethyl)phenyl]-1H-benzimidazol-1-yl}methyl)oxetan-3-ol; andj) (3S)-2-methyl-3-(6-{[5-(trifluoromethyl)pyridin-2-yl]oxy}-1H-benzimidazol-1-yl)butan-2-ol;or a pharmaceutically acceptable salt of the compound of a)-j).2. The compound of wherein the compound is 1-[6-(4-fluorophenoxy)-1H-benzimidazol-1-yl]-2-methylpropan-2-ol claim 1 , or a pharmaceutically acceptable salt thereof.3. The compound of wherein the compound is 1-[6-(4-chlorophenoxy)-1H-benzimidazol-1-yl]-2-methylpropan-2-ol claim 1 , or a pharmaceutically acceptable salt thereof.4. The compound of wherein the compound is 2-methyl-1-(6-{[5-(trifluoromethyl)pyridin-2-yl]oxy}-1H-benzimidazol-1-yl)propan-2-ol claim 1 , or a pharmaceutically acceptable salt thereof.5. The compound of wherein the compound is 2-methyl-4-(6-{[5-(trifluoromethyl)pyridin-2-yl]oxy}-1H-benzimidazol-1-yl)butan-2-ol claim 1 , or a pharmaceutically acceptable salt thereof.6. The compound of wherein the compound is 3-({6-[4-( ...

Organic light-emitting device

Provided is an organic light emitting device including a positive electrode, a negative electrode, and an organic material layer provided between the positive electrode and the negative electrode, wherein the organic material layer comprises a hole transport material having a HOMO absolute value of 4.30 eV to 4.60 eV, and a reversibility value (I r /I f ) of 0.83 or higher within an oxidation range at a scan rate of 100 mV/s, or the organic material layer comprises an electron blocking material having a reversibility value (I r /I f ) of more than 0.5 within an oxidation range at a scan rate of 100 mV/s, or the organic material layer comprises an electron transport material having a LUMO absolute value of 2.60 eV to 2.90 eV, and a reversibility value (I r /I f ) larger than [ 4.96−1.535 ×(the LUMO absolute value)] within a reduction range at a scan rate of 100 mV/s.

Use of Organic Compound for the Treatment of Noonan Syndrome

The use of a MEK inhibitor compound of Formula (I), as defined herein, or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the treatment of Noonan Syndrome, a method of treating a warm-blooded animal, especially a human, having Noonan Syndrome, comprising administering to said animal a therapeutically effective amount of a MEK inhibitor compound of Formula (I), as defined herein, or a pharmaceutically acceptable salt thereof; and to a pharmaceutical composition and a commercial package comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and a package insert or other labeling including directions for treating Noonan Syndrome.

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.

AROMATIC SULFONAMIDE DERIVATIVES

Substituted aromatic sulfonamides of formula (I) pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease. 7: The compound according to claim 1 , wherein:{'sup': '2', 'Ris phenyl,'}{'sup': 11', '11a', '11', '11, 'wherein said phenyl group is optionally independently substituted one to three times with R, or independently substituted one time with Rand optionally one to two times with R, or substituted with two adjacent substituents Rwhich together represent a methylendioxy group to form a 5-membered ring.'}8: The compound according to claim 1 , wherein:{'sup': '2', 'Ris a 5-membered monocyclic heteroaryl,'}{'sup': '11', 'claim-text': {'sup': 11a', '11, 'independently substituted one time with Rand optionally one to two times with R.'}, 'wherein said heteroaryl is optionally independently substituted one to three times with R, or'}11: The compound according to claim 1 , wherein:{'sup': '2', 'Ris a 6-membered monocyclic heteroaryl,'}{'sup': '11', 'claim-text': {'sup': 11a', '11, 'independently substituted one time with Rand optionally one to two times with R.'}, 'wherein said heteroaryl group is optionally independently substituted one to three times with R, or'}12: The compound according to claim 1 , wherein:{'sup': '2', 'Ris a [5,6]-annellated bicyclic heteroaryl,'}{'sup': '11', 'claim-text': {'sup': 11a', '11, 'independently substituted one time with Rand optionally one to two times with R.'}, 'wherein said heteroaryl group is optionally independently substituted one to three times with R, or'}13: The compound according to claim 1 , wherein:{'sup': '3', 'Ris hydrogen; and'}{'sup': '4', 'Ris hydrogen, methyl, or OH.'}14: The compound according to claim 1 , wherein:{'sup': '8', 'sub': 1', '4', '3', '6', '1', '4, 'Ris C-C-alkyl, C-C-cycloalkyl, or C-C-haloalkyl.'}15: The compound according to claim 1 , wherein:{'sup': '9', 'sub': 1', ...

INHIBITORS OF WDR5 PROTEIN-PROTEIN BINDING

The present application is directed to compounds of Formula I: (I) compositions comprising these compounds and their uses, for example as medicaments for the treatment of diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners. 2. The compound of claim 1 , wherein Ris a heterocycloalkyl that is unsubstituted or substituted with one claim 1 , two or three substituents selected from halo claim 1 , Calkyl claim 1 , Cfluoroalkyl claim 1 , CalkyleneOR claim 1 , NRRand CalkyleneNRR claim 1 , provided that Rcomprises at least one basic nitrogen atom.3. (canceled)4. (canceled)6. (canceled)7. (canceled)8. The compound of claim 1 , wherein Ris selected from Caryl and heteroaryl claim 1 , and Ris unsubstituted or substituted with one claim 1 , two or three substituents selected from halo claim 1 , Calkyl claim 1 , Cfluoroalkyl claim 1 , ═O claim 1 , OR claim 1 , SRand NRR.9. (canceled)10. (canceled)12. (canceled)13. (canceled)14. The compound of claim 1 , wherein Ris selected from H claim 1 , Calkyl and C(O)Calkyl.15. The compound of claim 1 , wherein Rand Rare independently selected from H claim 1 , Calkyl and heterocycloalkyl.16. (canceled)17. The compound of claim 1 , wherein Rand Rtogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one claim 1 , two or three substituents selected from halo and Calkyl.18. (canceled)19. The compound of claim 1 , wherein Ris selected from H and Calkyl.20. The compound of claim 1 , wherein one of X claim 1 , X claim 1 , Xand Xis N and the others of X claim 1 , X claim 1 , Xand Xis CR.21. The compound of claim 1 , wherein X claim 1 , X claim 1 , Xand Xare CR.22. The compound of claim 1 , wherein one of X claim 1 , Xand Xis N and the others of X claim 1 , Xand Xare CH.23. The compound of claim 1 , wherein X claim 1 , Xand Xare CH.24. The compound of claim 1 , wherein Ris selected from H claim 1 ...

FIVE-MEMBERED HETEROCYCLES USEFUL AS SERINE PROTEASE INHIBITORS

The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): 2. A compound according to claim 1 , wherein:{'sup': 10', '10', '10', '10, 'sub': 2', '2, 'L is —C(O)NR—, —NRC(O)—, —CHCONR—, or —NRCOCH—;'}{'sup': 3', '8', '9', '8', '3b', '3b', '3a', '3d', '3a', '3d', '3a', '3d, 'sub': 2', 'r', '2', 'r', '2', 's', '2', '2', 'r', '2', '2', 'r', '2', 'r', '2', 'r', '2', 'r, 'Ris —(CH)C(O)NRR, —(CH)C(O)NR(CH)COR, —(CH)COR, —(CH)-phenyl substituted with 0-3 Rand 0-1 R, —(CH)-naphthyl substituted with 0-3 Rand 0-1 R, —(CH)-indanyl substituted with 0-3 Rand 0-1 R, or —(CH)-5-10 membered heterocycle comprising{'sub': 'p', 'sup': 3a', '3d, 'carbon atoms and 1-4 heteroatoms selected from N, O, and S(O), wherein said heterocycle is substituted with 0-3 Rand 0-1 R;'}{'sup': 4', 'a', 'a', 'a', 'a', '7', '8', '8', '9', '7', 'b', '8', '9', '8', 'c', 'c', 'c', '4a', '4a', '4a', '4b', '4b, 'sub': 3', '3', '2', 'p', 'p', '2', '1-6', '2-6', '2-6', 'p, 'Ris H, F, Cl, Br, I, OCF, CF, OR, SR, CN, NO, —C(O)R, —C(O)OR, —NRR, —C(O)NRR, —NRC(O)R, —S(O)NRR, —NRS(O)R, —S(O)R, —S(O)R, Calkyl substituted with 0-2 R, Calkenyl substituted with 0-2 R, Calkynyl substituted with 0-2 R, phenyl substituted with 0-2 R, or a 5-10 membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, O, and S(O), wherein said heterocycle is substituted with 0-3 R;'}{'sup': 10', '10a', 'd', 'd, 'sub': 1-6', '2', 'r', '2', 'r', 'p, 'Ris, independently at each occurrence, H, Calkyl substituted with 0-2 R, —(CH)-phenyl substituted with 0-2 R, or —(CH)-5-10 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O), wherein said heterocycle is substituted with 0-2 R; and'}{'sup': 11', '8', '9', '11a', '11a', '11a', '11b, 'sub': 1-4', '2', 'r', '1-6', '2-6', '2-6', '2', 'r', 'p, 'Ris Chaloalkyl, —(CH)— ...

IMIDAZOLYL TRICYCLIC ENONES AS ANTIOXIDANT INFLAMMATION MODULATORS

Disclosed herein are compounds of the formula: (I), wherein the variables are defined herein. Also provided are pharmaceutical compositions thereof. In some aspects, the compounds and compositions provided herein may be used as antioxidant inflammation modulators. In some aspects, the present disclosure provides methods wherein the compounds and composition described herein are used for the treatment of diseases and disorders associated with inflammation and cancer. 972-. (canceled)73. The compound of claim 4 , wherein the carbon atom labeled 4 is in the S configuration.74. The compound of claim 4 , wherein the carbon atom labeled 5 is in the S configuration.75. The compound of claim 4 , wherein the carbon atom labeled 10 is in the R configuration.78. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) a compound of ; and'}b) an excipient.79. A method of treating a disease or disorder comprising administering to a patient in need thereof a therapeutically effective amount of a compound of .80. (canceled)81. The method of claim 79 , wherein the patient is a human.82. The method of claim 79 , where in the disease or disorder is associated with inflammation.83. The method of claim 79 , wherein the disease or disorder is characterized by overexpression of iNOS genes in the patient.84. The method of claim 79 , wherein the disease or disorder is characterized by overexpression of COX-2 genes in the patient.85. (canceled) This application claims the benefit of U.S. Provisional Application Ser. No. 62/115,247, filed on Feb. 12, 2015, the entire contents of which is hereby incorporated by reference.The present invention relates generally to the fields of biology and medicine. More particularly, it concerns compounds, compositions and methods for the treatment and prevention of diseases such as those associated with oxidative stress and inflammation.The anti-inflammatory and anti-proliferative activity of the naturally occurring ...

Nanomaterials containing constrained lipids and uses thereof

Compositions for delivering nucleic acids to cells or tissue microenvironments are provided. In one embodiment, the compositions are lipid nanoparticle compositions formulated to have reduced splenic and hepatic clearance. It has been discovered that the chemical composition of lipid nanoparticles significantly influences the natural trafficking of the lipid nanoparticles. More specifically, it has been discovered that conformationally constrained ionizable lipids can modify the tropism and clearance profile of lipid nanoparticles without the need of a targeting ligand. It has also been discovered that tropism of the disclosed lipid nanoparticles is size-independent.

NOVEL INHIBITORS

The invention relates to a compound of formula (1): 12. The compound according to claim 1 , which is a compound selected from:5-[3-({4′-fluoro-[1,1′-biphenyl]-2-yl}amino)propyl]-1,3,4-thiadiazol-2-amine;5-{[2-({4′-fluoro-[1,1′-biphenyl]-2-yl}amino)ethyl]sulfanyl}-1,3,4-thiadiazol-2-amine;5-{[2-({3′,4′-dimethoxy-[1,1′-biphenyl]-2-yl}amino)ethyl]sulfanyl}-1,3,4-thiadiazol-2-amine;5-[4-({4′-fluoro-[1,1′-biphenyl]-2-yl}amino)phenyl]-1,3,4-thiadiazol-2-amine;5-(4-{[2-(3,4-dimethoxyphenyl)phenyl]amino}phenyl)-1,3,4-thiadiazol-2-amine;5-(4-{[2-(4-methoxyphenyl)phenyl]amino}phenyl)-1,3,4-thiadiazol-2-amine;N-[4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl]-3-(4-methoxyphenyl)pyridin-2-amine;N-[4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl]-3-(4-methoxyphenyl)pyridin-4-amine;N-[4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl]-3-(3,4-dimethoxyphenyl)pyridin-4-amine;N-[4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl]-3-(4-fluorophenyl)pyridin-2-amine;N-[4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl]-3-(4-fluorophenyl)pyrazin-2-amine;5-(4-{[2-(4-phenoxyphenyl)phenyl]amino}phenyl)-1,3,4-thiadiazol-2-amine;5-(4-{[2-(4-propoxyphenyl)phenyl]amino}phenyl)-1,3,4-thiadiazol-2-amine;5-[4-({2-[4-(propan-2-yloxy)phenyl]phenyl}amino)phenyl]-1,3,4-thiadiazol-2-amine;N-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]-4-fluorobenzene-1-sulfonamide;N-{2-[(5-amino-1,3,4-thiadiazol-2-yl)sulfanyl]ethyl}-4-fluorobenzene-1-sulfonamide;5-(3-{[(4-fluorophenyl)(methyl)oxo-λω-sulfanylidene]amino}propyl)-1,3,4-thiadiazol-2-amine;N-[4-(2-amino-1,3-thiazol-5-yl)phenyl]-4-fluorobenzene-1-sulfonamide;N-[4-(2-amino-1,3-thiazol-5-yl)phenyl]-3,4-dimethoxybenzene-1-sulfonamide;5-(1-{4′-fluoro-[1,1′-biphenyl]-2-yl}piperidin-4-yl)-1,3,4-thiadiazol-2-amine;5-[1-(4-fluorobenzenesulfonyl)piperdino-4-yl]-1,3-thiazol-2-amine;5-[1-(4-fluorobenzenesulfonyl)piperidin-4-yl]-1,3,4-thiadiazol-2-amine;or a pharmaceutically acceptable salt or solvate thereof, including all tautomers and stereoisomers.13. A pharmaceutical composition comprising a compound according ...

HETEROCYCLIC CARBOXYLIC ACID AMIDE LIGAND AND APPLICATIONS THEREOF IN COPPER CATALYZED COUPLING REACTION OF ARYL HALOGENO SUBSTITUTE

Provided are a heterocyclic carboxylic acid amide ligand and applications thereof in a copper catalyzed coupling reaction. Specifically, provided are uses of a compound represented by formula (I), definitions of radical groups being described in the specifications. The compound represented by formula (I) can be used as the ligand in the copper catalyzed coupling reaction of the aryl halogeno substitute, and is used or catalyzing the coupling reaction for forming the aryl halogeno substitute having C—N, C—O, C—S and other bonds. 5: The method of claim 4 , wherein in the reaction claim 4 , the molar ratio of the ligand to the reactant aryl halide is 1-50:100 claim 4 , preferably 5-20:100; and/orthe molar ratio of the ligand to the copper catalyst is 1-5:1, preferably 1-2:1.7: The method of claim 4 , wherein the reaction temperature is 50-180° C. claim 4 , preferably 100-130° C.9: The method of wherein the copper catalyst is selected from the group consisting of CuI claim 4 , CuBr claim 4 , CuCl claim 4 , CuTc claim 4 , Cu(OAc) claim 4 , CuSO claim 4 , CuO claim 4 , CuBr claim 4 , CuCl claim 4 , CuO claim 4 , CuSCN claim 4 , CuCN claim 4 , Cu(acac) claim 4 , and combinations thereof; preferably CuI.10: The method of claim 4 , wherein the reaction is carried out in the presence of a base.11: The method of claim 8 , wherein claim 8 ,in the reaction (1), the ligand is preferably L-53 or L-103; and/orin the reaction (2), the ligand is preferably: L-13, L-15 or L-31; and/orin the reaction (3), the ligand is preferably: L-13, L-15 or L-35; and/orin the reaction (4), the ligand is preferably: L-92, and/or L-105; and/orin the reaction (5), the ligand is preferably L-13, L-112, L-114. The present invention relates to the field of organic synthesis. In particular, a copper-catalyzed coupling reaction of aryl halide catalyzed by a heterocyclic carboxylic acid amide ligand, especially a coupling reaction to form C—N, C—O, and C—S bonds is provided in the present invention. ...

Organic electroluminescent element and electronic device

An organic electroluminescence device includes: an anode; an emitting layer; and a cathode, the emitting layer containing a first material, a second material and a third material, the first material being a fluorescent material, the second material being a delayed fluorescent material, the third material having a singlet energy larger than a singlet energy of the second material.

IMIDAZOQUINOLYL COMPOUNDS HAVING ANTI-INFLAMMATORY, ANTIFUNGAL, ANTIPARASITIC, AND ANTICANCER ACTIVITY

Amine compounds having activity against inflammation, fungi, unicellular parasitic microorganisms, and cancer are described. The compounds contain a monocyclic, bicyclic, or tricyclic aromatic ring having one, two, or three ring nitrogen atoms. 2. The compound or salt of claim 1 , wherein Ris hydrogen.3. The compound or salt of claim 2 , wherein the compound is selected from the group consisting of:1-[2-(Ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol,1-(4-Amino-1-isobutyl-1H-imidazo[4,5-c]quinolin-2-yl)pentyl acetate,1-Isobutyl-2-pentadecyl-1H-imidazo[4,5-c]quinolin-4-ol,1-Octyl-1H-imidazo[4,5-c]quinoline,1-Hexadecyl-1H-imidazo[4,5-c]quinoline,1-Hexadecyl-1H-imidazo[4,5-c]quinolin-4-amine,1-Dodecyl-1H-imidazo[4,5-c]quinoline,1-{5-[3-(Hexyloxy)propoxy]pentyl}-1H-imidazo[4,5-c]quinoline,1-{3-[3-(Hexyloxy)phenoxy]propyl}-1H-imidazo[4,5-c]quinoline.4. The compound or salt of claim 2 , wherein Ris an unbranched alkyl having from 2 to 10 carbon atoms claim 2 , substituted by alkoxy having from 1 to 12 carbon atoms.5. The compound or salt of claim 4 , wherein the compound is selected from the group consisting of:1-[2-(Dodecyloxy)ethyl]-1H-imidazo[4,5-c]quinoline,1-[2-(Dodecyloxy)ethyl]-N,N-dimethyl-1H-imidazo[4,5-c]quinolin-4-amine,1-[6-(Octyloxy)hexyl]-1H-imidazo[4,5-c]quinoline,1-(8-Ethoxyoctyl)-1H-imidazo[4,5-c]quinoline,1-(8-Methoxyoctyl)-1H-imidazo[4,5-c]quinoline,1-(8-Butoxyoctyl)-1H-imidazo[4,5-c]quinoline,1-[9-(Hexyloxy)nonyl]-1H-imidazo[4,5-c]quinoline,1-(10-Butoxydecyl)-1H-imidazo[4,5-c]quinoline,1-[3-(Decyloxy)propyl]-1H-imidazo[4,5-c]quinoline,1-[4-(Decyloxy)butyl]-1H-imidazo[4,5-c]quinoline,1-[8-(Hexyloxy)octyl]-1H-imidazo[4,5-c]quinoline.6. A pharmaceutical composition comprising an effective amount of the compound or pharmaceutically acceptable salt of any one of - and a pharmaceutically acceptable carrier.7. A method for treating or preventing a condition in a mammalian subject; the condition being selected from the group consisting of an ...

N-biphenylmethylbenzimidazole modulators of pparg

The invention provides molecular entities that bind with high affinity to PPARG (PPARγ), inhibit cdk5 -mediated phosphorylation of PPARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes or obesity. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided.

NOVEL COMPOSITION FOR PREVENTING OR TREATING HEPATITIS C VIRUS, REGULATING PHOSPHORYLATION OF REPLICASE

The present invention relates a novel composition for preventing or treating hepatitis C virus, regulating the phosphorylation of a replicase. More specifically, it is possible to prevent or treat hepatitis C using a novel PRK2 inhibitor discovered through structure modeling, and to prevent or treat hepatitis C, particularly, interferon-insensitive hepatitis C through coadministration of an Hsp90 inhibitor. 2. The composition for preventing or treating hepatitis C virus of claim 1 , wherein Arrepresents aryl or nitrogen-containing heteroaryl having 6 to 10 carbon atoms claim 1 , or a nitrogen-containing substituted heterocyclic having 6 to 10 carbon atoms claim 1 ,{'sub': '1', 'Rrepresents alkyl having 1 to 2 carbon atoms substituted with —NH—(O)— or nitrile, and'}{'sub': 2', '2', '2, 'Arrepresents cycloalkyl having 6 to 12 carbon atoms, a nitrogen-containing substituted heterocyclic having 6 to 12 carbon atoms, nitrogen-containing heteroaryl having 6 to 10 carbon atoms, heteroaryloxy containing at least one of oxygen, nitrogen, and sulfur atoms and having 6 to 10 carbon atoms substituted or unsubstituted with aryl having 6 to 10 carbon atoms, or aryl having 6 to 10 carbon atoms substituted with —NH—(O)—R, and the Rrepresents alkyl having 1 to 2 carbon atoms.'}3. The composition for preventing or treating hepatitis C virus of claim 1 , wherein the compound expressed by Chemical Formula 1 is any one of 3-[(2-ethylbutanoyl)amino-N-(pyridine-4-yl)benzamide] claim 1 , cyclohexanecarboxylic acid (1H-benzoimidazole-5-yl)-amide claim 1 , (3r claim 1 ,5r claim 1 ,7r)-N-(quinolin-5-yl)adamantane-1-carboxamide claim 1 , 1-methyl-4-phenylpiperidine-4-carbonitrile) claim 1 , 2-oxo-N-4-pyridinyl-3-piperidinecarboxamide claim 1 , N-(2-oxoazepan-3-yl)pyridine-4-carboxamide claim 1 , 2-oxo-N-(pyridine-4-yl)-2H-chromene-3-carboxamide claim 1 , 2-oxo-N-(4-pyridinyl)-1 claim 1 ,2-dihydro-3-pyridinecarboxamide claim 1 , 1-benzyl-2-oxo-N-(4-pyridinyl)-1 claim 1 ,2-dihydro-3- ...

Heterocyclic Derivative and Pharmaceutical Drug

The present invention provides a novel heterocyclic derivative or a pharmaceutically acceptable salt thereof. For example, the present invention provides a heterocyclic derivative of the general formula [1] or its tautomer, or a pharmaceutically acceptable salt thereof: 2. The heterocyclic derivative according to claim 1 , wherein the ring A is a group of formula [4] and Xis NH claim 1 , or its tautomer or a pharmaceutically acceptable salt thereof.7. The heterocyclic derivative according to selected from the following (1)-(239) claim 1 , or its tautomer or a pharmaceutically acceptable salt thereof:(1) N-[2-(trifluoromethyl)benzyl]-6-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-benzimidazole-4-carboxamide,(2) N-cyclohexyl-6-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-benzimidazole-4-carboxamide,(3) N-(3-chloro-2-methylphenyl)-6-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-benzimidazole-4-carboxamide,(4) N-[(1-hydroxycyclohexyl)methyl]-6-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-benzimidazole-4-carboxamide,(5) N-[2-(trifluoromethyl)benzyl]-5-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-2,3-dihydro-1-benzofuran-7-carboxamide,(6) N-cyclohexyl-5-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-2,3-dihydro-1-benzofuran-7-carboxamide,(7) N-(3-chloro-2-methylphenyl)-5-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-2,3-dihydro-1-benzofuran-7-carboxamide,(8) N-cyclohexyl-5-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-indazole-7-carboxamide,(9) N-[2-(trifluoromethyl)benzyl]-5-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-indazole-7-carboxamide,(10) N-(3-chloro-2-methylphenyl)-2-(methoxymethyl)-6-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-benzimidazole-4-carboxamide,(11) 2-methyl-N-[2-(trifluoromethyl)benzyl]-6-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-benzimidazole-4-carboxamide,(12) N-cyclohexyl-2-methyl-6-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-benzimidazole-4-carboxamide,(13) N-(3-chloro-2-methylphenyl)-2-methyl-6-({[2-(trifluoromethyl) ...

NOVEL HYDROGEN SULFATE SALT

The present invention relates to Compound 1 hydrogen sulfate salt and solvates, crystalline forms and amorphous forms thereof, and to processes for their preparation. 2. A hydrogen sulfate salt of Compound 1 according to in anhydrous form.3. A hydrogen sulfate salt of Compound 1 according to in the form of a solvate.4. A hydrogen sulfate salt of Compound 1 according to which is crystalline.5. A hydrogen sulfate salt of Compound 1 according to claim 4 , wherein said hydrogen sulfate salt of Compound 1 has an X-ray powder diffraction pattern with at least one specific peak at about 24.59°.6. A hydrogen sulfate salt of Compound 1 according to claim 5 , wherein said hydrogen sulfate salt of Compound 1 has an X-ray powder diffraction pattern with specific peaks at about 2-theta equal to 24.59° claim 5 , 20.97° claim 5 , 23.99° claim 5 , 27.65° claim 5 , 12.24° claim 5 , 23.49° claim 5 , 24.30° claim 5 , 17.02° claim 5 , 25.91° and 22.50°.7. A hydrogen sulfate salt of Compound 1 according to which has a powder X-ray diffraction pattern substantially the same as the X-ray powder diffraction pattern shown in .8. A hydrogen sulfate salt of Compound 1 according to in amorphous form.9. A method for preparing a hydrogen sulfate salt of Compound 1 according to claim 1 , said method comprising(i) reacting a slurry of Compound 1 in an organic liquid with at least a stoichiometric amount of sulfuric acid and water;(ii) recovering the salt from the resultant solution; and(iii) thereafter, if desired or necessary, forming a solvate thereof.10. The method according to wherein the amount of water added in step (i) is restricted to that amount necessary to ensure that the salt is formed.11. The method according to wherein step (i) is carried out at a temperature of from 40-80° C.12. The method according to claim 9 , wherein the organic liquid is a Calkyl ketone.13. The method according to claim 9 , wherein the hydrogen sulfate salt is recovered in step (ii) by cooling the reaction ...

MODULATORS OF THE RELAXIN RECEPTOR 1

Disclosed are modulators of the human relaxin receptor 1, for example, of formula (I), wherein A, R, and Rare as defined herein, that are useful in treating mammalian relaxin receptor 1 mediated facets of human health, e.g., cardiovascular disease. Also disclosed is a composition comprising a pharmaceutically suitable carrier and at least one compound of the disclosure, and a method for therapeutic intervention in a facet of mammalian health that is mediated by a human relaxin receptor 1. 120-. (canceled)21. A method for therapeutic intervention in a facet of mammalian health that is mediated by a mammalian relaxin receptor 1 claim 104 , the method comprising administering to a mammal in need thereof an effective amount of a compound or salt of .2239-. (canceled)40. The method of claim 21 , whereinthe facet of mammalian health is cardiovascular disease.41. The method of claim 40 , wherein the cardiovascular disease is selected from myocardial ischemia-reperfusion injury claim 40 , cardiac fibrosis claim 40 , acute congestive heart failure claim 40 , cerebrovascular disease and stroke claim 40 , post-infarction heart claim 40 , cardiac anaphylaxis claim 40 , cerebral ischemia (stroke) claim 40 , intestinal ischemia-reperfusion injury claim 40 , systemic and pulmonary hypertension claim 40 , vascular inflammation claim 40 , hypertension claim 40 , high blood pressure; left ventricular hypertrophy (LVH); vasodilation; renal hypertension; diuresis; nephritis; natriuresis; scleroderma renal crisis; angina pectoris (stable and unstable); myocardial infarction; heart attack; coronary artery disease; coronary heart disease; cardiac arrhythmias; atrial fibrillation; portal hypertension; raised intraocular pressure; vascular restenosis; chronic hypertension; valvular disease; myocardial ischemia; acute pulmonary edema; acute coronary syndrome; hypertensive retinopathy; hypertensive pregnancy sickness; Raynaud's phenomenon; erectile dysfunction claim 40 , glaucoma claim 40 , ...

Organic electroluminescent element and electronic device using same

An organic electroluminescence device comprising: a cathode, an anode, and an organic layer disposed between the cathode and the anode, wherein the organic layer comprises a compound represented by the following formula (1), and a compound A having a Stokes shift of 20 nm or smaller and an emission peak wavelength of 440 nm to 465 nm (at least one of Ar1 and Ar2 is a monovalent group having a structure represented by the following formula (2)).

NOVEL ONE-POT HOMOGENEOUS PROCESS FOR THE LARGE SCALE MANUFACTURE OF 2-SUBSTITUTED BENZIMIDAZOLES

2-substituted benzimidazoles and methods of preparing the same are disclosed. The compositions may include a compound or salt thereof, an acid, and a polar aprotic solvent. The compositions may be used to inhibit corrosion of a metal surface in contact with an aqueous system, and provide enhanced protection against corrosion of metals in the aqueous system. 2. The composition of claim 1 , further comprising water.3. The composition of claim 1 , whereinX is independently hydrogen or halogen;{'sup': '1', 'Ris hydrogen;'}{'sup': '2', 'Ris absent; and'}{'sup': 3', '4, 'Ris CHR.'}4. The composition of claim 1 , wherein at least one Z is nitrogen.5. The composition of claim 1 , wherein Ris a bond and at least one Z is nitrogen.7. The composition of claim 1 , wherein the acid is selected from sulfuric acid claim 1 , hydrochloric acid claim 1 , nitric acid claim 1 , methanesulfonic acid claim 1 , phosphoric acid claim 1 , sulfamic acid claim 1 , aminomethylphosphonic acid claim 1 , p-toluenesulfonic acid claim 1 , and any combination thereof.8. The composition of claim 1 , wherein the polar aprotic solvent is selected from acetonitrile claim 1 , N claim 1 ,N-dimethylformamide claim 1 , acetone claim 1 , dimethylsulfoxide claim 1 , sulfolane claim 1 , N-methylpyrrolidinone claim 1 , methylsulfonylmethane claim 1 , chlorobenzene claim 1 , o-dichlorobenzene claim 1 , nitromethane claim 1 , an ionic liquid claim 1 , and any combination thereof.9. The composition of claim 1 , wherein the composition is homogenous liquid.10. The composition of claim 1 , further comprising a high temperature stable phase transfer catalyst.11. The composition of claim 10 , wherein the high temperature stable phase transfer catalyst is selected from the group consisting of an alkyl guanidinium salt claim 10 , an aryl guanidinium salt claim 10 , an alkyl phosphonium salt claim 10 , an aryl phosphonium salt claim 10 , a peralkylated phosphazenium salt claim 10 , and any combination thereof.13. The ...

HETEROCYCLIC COMPOUND

One of the purposes of the present invention is to provide a heterocyclic derivative that has an IAP (particularly XIAP) binding (inhibiting) activity. Another of the purposes of the present invention is to provide a heterocyclic derivative that has an IAP (particularly XIAP) binding (inhibiting) activity and exhibits a protein degradation induction activity. The present invention provides a compound represented by formula (I) (the symbols in the formula are as defined in the present Description) and salts thereof. 12: A medicament comprising the compound or salt thereof according to .13: The medicament according to claim 12 , wherein it is an IAP inhibitor.14: The medicament according to claim 12 , wherein it is a targeted protein degrader.15: The medicament according to claim 12 , wherein it is a prophylactic or therapeutic agent for cancers.16: The medicament according to claim 12 , wherein it is a prophylactic or therapeutic agent for pathogenic protein-related diseases.17: A method of inhibiting IAP(s) in mammals claim 2 , comprising administering an effective amount of the compound or salt thereof according to to the mammals.18: A method of inducing targeted protein degradation in mammals claim 2 , comprising administering an effective amount of the compound or salt thereof according to to the mammals.19: A method of prophylaxis or treatment of cancers in mammals claim 2 , comprising administering an effective amount of the compound or salt thereof according to to the mammals.2021-. (canceled)22: A method for producing a protein degrader claim 2 , comprising using the compound or salt thereof according to as at least a part of the protein degrader.2324-. (canceled) The present invention relates to a novel heterocyclic compound and its use.Development of compounds that induce ubiquitination of target proteins and proteasome degradation by E3 ligase (referred to as Proteolysis Targeting Chimeras (PROTAC (registered trademark) or Specific and Nongenetic IAP- ...

METHOD FOR PREPARATION OF BENZIMIDAZOLE DERIVATIVES

The present invention provides a method for preparing a compound with a benzimidazole structure with an excellent yield using a low-cost starting material, not requiring an additional separation process, or not using a dangerous reagent during the manufacturing process. Furthermore, the present invention also provides an intermediate and a final product produced by the preparing method. 5. The method of claim 1 , wherein Rand Rare independently methyl claim 1 , ethyl claim 1 , propyl or tert-butyl.6. The method of claim 1 , wherein Ris methyl claim 1 , trifluoromethyl or phenyl.7. The method of claim 1 , wherein step 1) is performed in the presence of a base selected from the group consisting of potassium tert-butoxide claim 1 , sodium ethoxide and sodium methoxide.8. The method of claim 1 , wherein step 1) is performed using a solvent selected from the group consisting of methanol claim 1 , ethanol claim 1 , acetonitrile and methylene chloride.9. The method of claim 1 , wherein step 2) is performed using acetonitrile as a solvent.11. The method of claim 10 , wherein Ris methyl claim 10 , ethyl claim 10 , propyl or tert-butyl.12. The method of claim 10 , wherein Ris methyl or ethyl.13. The method of claim 10 , wherein hydrochloric acid claim 10 , bromic acid or acetic acid is added in step a).14. The method of claim 10 , wherein acetyl chloride is added in step a).15. (canceled)16. The method of claim 10 , wherein step c) is performed in the presence of a base selected from the group consisting of potassium carbonate claim 10 , triethylamine claim 10 , sodium hydroxide and diisopropylethylamine.17. (canceled)18. (canceled)19. The method of claim 3 , wherein the reaction is performed using a solvent selected from the group consisting of methanol claim 3 , ethanol claim 3 , water and a mixed solution thereof.21. The compound of claim 20 , wherein Rand Rare independently methyl claim 20 , ethyl; propyl or tert-butyl.22. The compound of claim 20 , wherein Ris methyl ...

NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS

The present invention discloses compounds according to Formula I: 2. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris Me.6. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris H claim 1 , F claim 1 , or Cl.7. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris H claim 1 , Me claim 1 , or Et.8. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris CN claim 1 , F claim 1 , Cl claim 1 , —SOMe or —SOEt.10. A compound or pharmaceutically acceptable salt according to claim 1 , wherein the compound is (1R claim 1 ,2R)—N-[6-[(6-cyano-4-methyl-3-pyridyl)oxy]-1-methyl-benzimidazol-4-yl]-2-fluoro-cyclopropanecarboxamide.11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt according to .12. The pharmaceutical composition according to claim 11 , comprising a further therapeutic agent.13. (canceled)14. A method for treating or preventing allergic diseases claim 1 , inflammatory diseases claim 1 , autoimmune diseases claim 1 , proliferative diseases claim 1 , transplantation rejection claim 1 , diseases involving impairment of cartilage turnover claim 1 , congenital cartilage malformations claim 1 , and/or diseases associated with hypersecretion of IL6 or hypersecretion of interferons comprising administering an effective amount of the compound or pharmaceutically acceptable according to .15. The pharmaceutical composition according to claim 12 , wherein the further therapeutic agent is an agent for the treatment of allergic diseases claim 12 , inflammatory diseases claim 12 , autoimmune diseases claim 12 , proliferative diseases claim 12 , transplantation rejection claim 12 , diseases involving impairment of cartilage turnover claim 12 , congenital cartilage malformations claim 12 , and/or diseases associated with hypersecretion of IL6 or ...

Polymorphic forms of 3-[2-butyl-1-(2-diethylamino-ehtyl)-1h-benzoimidazol-5-yl]-n-hydroxy-acrylamide and uses thereof

Crystalline polymorph forms of 3-[2-butyl-1-(2-diethylamino-ethyl)-1H-benzoimidazol-5-yl]-N-hydroxy-acrylamide are described. Pharmaceutical compositions and the uses of such compounds, compound forms, and compositions for the treatment of diseases and conditions are also presented.

FTO Inhibitors

The invention provides compounds that inhibit FTO (fat mass and obesity), including pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof, particularly obesity, with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition. 4. The composition of wherein:R1 and R2 are independently H or Me;R3 is H, OH or NHR, wherein R is H or C1-C4 alkyl; andR4 is optionally substituted, heterocyclic C3-C18 hydrocarbyl comprising an n-membered ring wherein n=3-18, including 1 to n−1 heteroatoms independently selected from N, O, S and P.5. The composition of wherein the heterocyclic C3-C18 hydrocarbyl is:a 3 membered ring that is an optionally substituted aziridine, oxirane or oxaziridine;a 4 membered ring that is an optionally substituted azetidine, oxetane or oxazetidine;a 5 membered ring that is an optionally substituted pyrrole, 1,2-diazole (pyrazole), 1,3 diazole (imidazole), thiazole, isothiazole, oxazole, isoxazole, furan, dioxole or thiophene;a 6 membered ring that is an optionally substituted pyridine, diazine, triazine, oxazine, thiazine, dioxine, oxathiine or dithiine;a 9 membered ring that is an optionally substituted indole, benzothiazole, benzooxazole, benzofuran, benzodioxole, benzothiophene or benzodithiole; ora 10 membered ring that is an optionally substituted quinoline, quinoxaline, quinazoline, chromene, benzodioxine, thiochromene or benzodithiine.6. The composition of wherein the heterocyclic C3-C18 hydrocarbyl is:a 4 membered ring that is an optionally substituted azetidine, oxetane or oxazetidine.7. The composition of wherein the heterocyclic C3-C18 hydrocarbyl is:a 5 membered ring that is an optionally substituted pyrrole, 1,2-diazole (pyrazole), 1,3 diazole (imidazole), thiazole, isothiazole, oxazole, isoxazole, furan, dioxole or thiophene.8. ...

PARASITICIDAL COMPOSITIONS COMPRISING BENZIMIDAZOLE DERIVATIVES, METHODS AND USES THEREOF

The invention relates to oral, topical or injectable compositions for combating liver fluke parasites in mammals, comprising at least one benzimidazole derivative active agent. The invention also provides for an improved method for eradicating and controlling liver fluke parasite infections and infestations in a mammal comprising administering the compositions of the invention to the mammal in need thereof. 2. A compound according to wherein Ris phenoxy substituted with one or more methyl groups.3. A compound according to wherein Ris 2-bromophenoxy.4. A compound according to wherein Ris chlorine or fluorine.5. A compound according to that is 6-chloro-5-(2 claim 1 ,3-dimethylphenoxy)-2-methylthiobenzimidazole.6. A compound according to that is 6-chloro-5-(2-bromophenoxy)-2-methylthiobenzimidazole.7. A compound according to that is 6-chloro-5-hexyl-2-methylthiobenzimidazole. (#24)8. A composition for treating helminth infestation comprising an anthelmintically effective amount of the compound of and a pharmaceutically acceptable carrier.9. A composition for treating helminth infestation according to wherein the composition of formula (I) is combined with an additional active agent.10. A composition for treating helminth infestation according to wherein the active agent is a macrocyclic lactone.11. A composition for treating helminth infestation according to wherein the macrocyclic lactone is selected from the group consisting of abamectin claim 10 , dimadectin claim 10 , doramectin claim 10 , emamectin claim 10 , eprinomectin claim 10 , ivermectin claim 10 , latidectin claim 10 , lepimectin claim 10 , selamectin or ML-1 claim 10 ,694 claim 10 ,554.12. A composition for treating helminth infestation according to wherein the composition of formula (I) is combined with verapamil.13. A method for treating helminth infestation comprising the step of administering an anthelmintically effective amount of the compound of to an animal in need thereof.14. A method according to ...

COMPOUNDS

Compounds of general formula (I) wherein R, R, R, Rand X are as defined herein are inhibitors of the epithelial sodium channel (ENaC) and are useful for the treatment or prevention respiratory diseases and conditions, skin conditions and ocular conditions. 3. The compound according to claim 1 , wherein Ris H claim 1 , halo claim 1 , —R claim 1 , —C(O)OR claim 1 , or —OR.4. The compound according to claim 3 , wherein Ris H claim 3 , chloro claim 3 , C(O)OH claim 3 , methyl claim 3 , trifluoromethyl claim 3 , methoxy or trifluoromethoxy.5. The compound according to claim 1 , wherein Ris -LR.6. The compound according to claim 5 , wherein Lis:{'sup': 1', '1', '1', '1', '1', '1', '1', '1', '2', '1', '2', '1', '2', '1', '1', '2', '1', '3', '2, '—Z—, Q-, ZQ-, -QZ—, —ZQZ—, -QQ-, -QQZ—, or -QQZQZ—;'}{'sup': 1', '1', '1', '1', '2, '—OZQ-, or —OZQZ—;'}{'sup': 1', '7', '2', '1', '1', '7', '2, '—ZN(R)Z—, or -QZN(R)Z—;'}{'sup': 1', '1', '1', '1', '2', '1', '2', '1', '1', '7', '1', '1', '7', '1', '2, '—C(O)Q-, —C(O)QZ—, —C(O)QQ-, —C(O)QQZ—, —C(O)QN(R)C(O)Z—, or —C(O)QN(R)C(O)ZQ-;'}{'sup': 7', '1', '7', '1', '7', '1', '1', '7', '1', '1', '2', '7', '1', '1', '7', '1', '2', '7', '1', '2', '1', '7', '1', '1', '2', '2, '—C(O)N(R)Z—, —C(O)N(R)Q-, —C(O)N(R)ZQ-, —C(O)N(R)ZQZ—, —C(O)N(R)QZ—, —C(O)N(R)QQ-, —C(O)N(R)QQZ—, —C(O)N(R)ZQQZ—,'}{'sup': 7', '1', '2', '7', '1', '2', '7', '1', '1', '2', '8', '3', '7', '1', '8', '2', '7', '1', '1', '8', '2', '7', '1', '1', '2', '3', '7', '1', '1', '2', '3', '2, 'sub': 2', '2', 'n', '2', 'n, '—C(O)N(R)ZO(CHCHO)Z—, —C(O)N(R)ZO(CHO)Z—, —C(O)N(R)ZQZN(R)Z—, —C(O)N(R)ZN(R)Z—, —C(O)N(R)QZN(R)Z—, —C(O)N(R)ZQOQOQ-, or —C(O)N(R)ZQOQOQZ—;'}{'sup': 1', '1', '1', '1', '1', '2, '—C(O)OZ—, —C(O)OZQ-, or C(O)OZQZ—; or'}{'sup': 1', '2', '1', '1', '1', '2', '1', '1', '2', '3', '1', '1', '2', '1', '2', '3', '1, '-QC(O)O—, QC(O)Z—, -QC(O)QZ—, QC(O)QQ-, QC(O)ZQ- or QC(O)QQZ—.'}7. The compound according to claim 6 , wherein Lis:{'sup': 1', '1', '1', '1', '1', '2', '1', '2 ...

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro -3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound. 1. (canceled)2. A method of treating a proliferative disease in a patient in need thereof , comprising administering to said mammal a pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and a pharmaceutically acceptable carrier or excipient.3. The method according to claim 2 , wherein the proliferative disease is cancer.4. The method according to claim 3 , wherein the cancer is selected from melanoma claim 3 , pancreatic cancer claim 3 , ovarian cancer claim 3 , carcinoma of the fallopian tubes claim 3 , peritoneal cancer claim 3 , biliary cancer claim 3 , colon cancer claim 3 , or rectal cancer.5. The method according to claim 4 , wherein the cancer is melanoma.6. The method according to claim 5 , wherein said melanoma is BRAFV600 or NRAS-mutant melanoma.7. The method according to claim 6 , wherein the pharmaceutical composition is formulated as a tablet.8. The method according to claim 7 , wherein the pharmaceutical composition comprises approximately 15 mg crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.9. The method according to claim 8 , wherein the pharmaceutical composition further comprises lactose monohydrate claim 8 , microcrystalline cellulose claim 8 , colloidal silicon dioxide claim 8 , croscarmellose sodium claim 8 , and magnesium stearate.10. The method according to claim 9 , wherein said melanoma is NRAS-mutant melanoma.11. The ...

NOVEL BENZIMIDAZOLE COMPOUND AND MEDICAL USE THEREOF

The present invention provides a medicament for treating a disease involving Nav 1.7 such as neuropathic pain, nociceptive pain, inflammatory pain, small-fiber neuropathy, erythromelalgia, paroxysmal extreme pain disorder, dysuria, and multiple sclerosis, which comprises a compound of formula (I): 2. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': 1a', '1b', '1c', '1d, 'sub': 1-4', '1-4', '6-10', '6-10, 'R, R, R, and Rare each independently hydrogen, halogen, cyano, Calkyl, Calkoxy, Caryl, Caryloxy, 5- to 12-membered heteroaryl, or 5- to 12-membered heteroaryloxy;'}{'sup': 1a', '1b', '1c', '1d, 'wherein each alkyl moiety of the alkyl and the alkoxy of R, R, R, and Ris optionally substituted with 1 to 3 independently selected halogens;'}{'sup': 1a', '1b', '1c', '1d, 'sub': 1-4', '1-4', '1-4, 'wherein each aryl moiety of the aryl and the aryloxy and each heteroaryl moiety of the heteroaryl and the heteroaryloxy of R, R, R, and Ris optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, cyano, Calkyl optionally-substituted with 1 to 3 substituents independently selected from Substituent-group A, Calkoxy optionally-substituted with 1 to 3 substituents independently selected from Substituent-group A, and Calkylsulfonyl optionally-substituted with 1 to 3 substituents independently selected from Substituent-group A.'}3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': 1a', '1b', '1c', '1d', '1a', '1b', '1c', '1d, 'sub': 6-10', '6-10', '1-4, 'R, R, R, and Rare each independently hydrogen, Caryl, Caryloxy, 5- to 12-membered heteroaryl, or 5- to 12-membered heteroaryloxy, wherein each aryl moiety of the aryl and the aryloxy and each heteroaryl moiety of the heteroaryl and the heteroaryloxy of R, R, R, and Ris optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen and Calkyl optionally ...

Methods of Forming Carbene-Functionalized Composite Materials

Deposition of carbene monolayers that excluded starting anions, such as iodide ions, has been achieved. Anions such as iodide are a typical contaminant in carbene hydrogen carbonate salts when synthesized using the state-of-the-art method. A method is described for eliminating substantially all starting anion (e.g., iodide) contamination from the monolayer. Air stable, purified carbenes precursors were used to deposit an intact monolayer on the surface of some industrially relevant metals. The monolayer's ability to protect these metals against, for example, oxidation has been demonstrated. 1. A method for forming a carbene-functionalized composite material , comprising:forming a carbene precursor by{'sub': '2', 'claim-text': forming a purified carbene precursor comprising a final hydrogen carbonate anion that is substantially free of the starting anion;', 'placing a material having at least a metal surface in fluid communication with the purified carbene precursor, thermally decomposing the purified precursor in the presence of a material having at least a metal surface, or vacuum depositing the purified carbene precursor in the presence of a material having at least a metal surface; and', 'forming a carbene monolayer on the metal surface, the monolayer being uniform, stable, substantially free of contamination, and substantially free of the starting anion., 'oxidizing a starting anion of a carbene precursor in the presence of water and CO, or exchanging a starting anion of a carbene salt via a hydrogen carbonate-anion exchange resin, and'}2. The method of claim 1 , wherein the purified carbene precursor comprises ≤10% of the starting anion; or claim 1 , ≤5%; or claim 1 , ≤2%; or claim 1 , ≤1%; or claim 1 , ≤1.5%; or claim 1 , ≤0.1%.35.-. (canceled)7. The method of claim 6 , wherein for{'sup': o', 'q', '1', '2', '7', '8, 'claim-text': {'sup': 2', '3', '5', '6', '11', '12', '3', '4', '9', '10, 'Formula (IIa) or Formula (Va): m is 1; each Y is N; Yand Yare C; Rand ...

SYNTHESIS OF A COMPOUND THAT MODULATES THE ACTIVITY OF BROMODOMAIN-CONTAINING PROTEINS

The present disclosure provides processes for the preparation of a compound of formula I: 2. The process of claim 1 , wherein the process comprises a base.3. The process of claim 2 , wherein the base is a carbonate claim 2 , bicarbonate claim 2 , acetate or phosphate.4. The process of claim 3 , wherein the base is potassium carbonate claim 3 , sodium carbonate claim 3 , cesium carbonate claim 3 , potassium bicarbonate claim 3 , sodium bicarbonate claim 3 , sodium acetate claim 3 , potassium acetate claim 3 , a dibasic phosphate or a tribasic phosphate.5. The process of claim 4 , wherein the base is sodium carbonate.6. The process of claim 1 , wherein the process comprises a Pd(0) or a Pd(II) catalyst.7. The process of claim 1 , wherein the process comprises a solvent selected from tetrahydrofuran claim 1 , 2-methyltetrahydrofuran claim 1 , n-propanol claim 1 , toluene claim 1 , N claim 1 ,N-dimethylformamide claim 1 , N claim 1 ,N-dimethylacetamide claim 1 , dimethoxyethane claim 1 , isopropyl acetate claim 1 , n-butanol claim 1 , t-amyl alcohol claim 1 , methanol claim 1 , ethanol claim 1 , isopropanol claim 1 , acetone claim 1 , methyl ethyl ketone claim 1 , ethyl acetate claim 1 , and N-methyl-2-pyrrolidone claim 1 , or a combination thereof with water.8. The process of claim 7 , wherein the solvent is 2-methyltetrahydrofuran and water.9. The process of claim 1 , wherein the process comprises a temperature from about 40° C. to about 100° C.10. The process of claim 9 , wherein the temperature is from about 55° C. to about 65° C.12. The process of claim 11 , wherein step (a) comprises a solvent selected from a Calcohol or a mixture thereof13. The process of claim 11 , wherein step (a) comprises a temperature from about 20° C. to about 65° C.14. The process of claim 11 , wherein step (a) comprises methanol as a solvent and a temperature from about 45° C. to about 55° C.15. The process of claim 11 , wherein step (b) comprises a base.16. The process of claim 15 , ...

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound. 1. (canceled) This application is a continuation of U.S. application Ser. No. 15/842,715, filed Dec. 14, 2017, which is a continuation of U.S. application Ser. No. 15/445,393, filed Feb. 28, 2017, which continuation of U.S. application Ser. No. 15/053,441, filed Feb. 25, 2016, which is a continuation of U.S. application Ser. No. 14/974,655, filed Dec. 18, 2015, which is a divisional application of U.S. application Ser. No. 14/057,498, filed Oct. 18, 2013, which claims priority to U.S. Provisional Application No. 61/716,169, filed Oct. 19, 2012, which are incorporated herein by reference in their entirety.Provided herein are processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound.Growth factor-mediated proliferative signals are transmitted from the extracellular environment to the nucleus through several pathways, including the RAS/RAF/MEK pathway. The RAS/RAF/MEK kinase signal transduction pathway is activated through initial extracellular binding and stimulation of tyrosine receptor kinases (RTKs) by their respective cognate ligands. Upon autophosphorylation of specific tyrosine residues in the cytosolic domain of RTKs, the Grb2-Sos complex translocates to the plasma membrane, ...

NOVEL COMPOUNDS AND COMPOSITIONS FOR INHIBITION OF FASN

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

Compounds and methods for treatment of hedgehog pathway associated conditions

Provided herein is novel compounds of formula (I), (II), (III), (IV), and (V) as described in the specification, and pharmaceutically acceptable salts, solvates, and prodrugs and compositions thereof, and methods of measuring hedgehog pathway activation in tumor cells, examining tumor cell proliferation, differentiation and apoptosis and using the compounds and pharmaceutical compositions disclosed for treatment of diseases and disorders associated with the hedgehog signaling pathway.

SELECTIVE INHIBITORS OF HISTONE DEACETYLASE ISOFORM 6 AND METHODS THEREOF

The described invention provides histone deacetylase (HDAC) inhibitor compounds with substituted benzimidazole, benzimidazolone and benzotriazole heterocycles showing selective inhibition of histone deacetylase isoform HDAC6. The described invention further provides methods of making such compounds and methods of inhibiting HDAC, treating HDAC-associated diseases, including cell proliferative disorders, such as cancer, autoimmune or inflammatory diseases and neurodegenerative diseases. 5. The compound according to claim 1 , wherein the HDAC inhibitor inhibits the histone deacetylating activity of at least one HDAC isoform with an inhibition activity (IC) from about 0.005 μM to about 2.76 μM.6. The compound according to claim 1 , wherein the HDAC inhibitor inhibits the histone deacetylating activity of HDAC6 with an inhibition activity (IC) from about 0.000001 μM to about 0.001 μM.7. The compound according to claim 1 , wherein the HDAC inhibitor is selective toward HDAC6.8. The compound according to claim 7 , wherein a ratio of the inhibitory activity (IC) of the HDAC inhibitor obtained in the presence of an HDAC isoform selected from the group consisting of HDAC1 claim 7 , HDAC2 claim 7 , HDAC3 claim 7 , HDAC4 claim 7 , HDAC5 claim 7 , HDAC7 claim 7 , HDAC8 claim 7 , and HDAC9 claim 7 , to the inhibition activity (IC) value of the HDAC inhibitor selective toward HDAC6 obtained in vitro in the presence of HDAC6 (in vitro selectivity value) has a value of at least 100.9. The compound according to claim 7 , wherein a ratio of the inhibitory activity (IC) of the HDAC inhibitor obtained in the presence of an HDAC isoform selected from the group consisting of HDAC1 claim 7 , HDAC2 claim 7 , HDAC3 claim 7 , HDAC4 claim 7 , HDAC5 claim 7 , HDAC7 claim 7 , HDAC8 claim 7 , and HDAC9 claim 7 , to the inhibition activity (IC) value of the HDAC inhibitor selective toward HDAC6 obtained in vitro in the presence of HDAC6 (in vitro selectivity value) has a value of at least 30 ...

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

The present invention provides a compound, that is a 1-({halo-2-[(2-hydrocarbyl or substituted hydrocarbyl)oxy]phenyl}methyl)-(fused bicyclic nitrogen heteroaryl) carboxylic acid or an ester or sulfonamide thereof. The compound may be represented by the following formula 27. The compound according to claim , wherein the compound is:2-(5-Chloro-2-Isobutoxy-Benzyl)-2H-Indazole-5-Carboxylic Acid;2-(5-Bromo-2-Isobutoxy-Benzyl)-2H-Indazole-5-Carboxylic Acid;2-(5-Chloro-2-Cyclopropylmethoxy-Benzyl)-2H-Indazole-4-Carboxylic Acid;2-(5-Chloro-2-Isobutoxy-Benzyl)-2H-Indazole-4-Carboxylic Acid;2-[5-Chloro-2-(2-Ethyl-Butoxy)-Benzyl]-2H-Indazole-4-Carboxylic Acid;2-[5-Chloro-2-(4-Chloro-Benzyloxy)-Benzyl]-2H-Indazole-4-Carboxylic Acid;2-(5-Bromo-2-Isobutoxy-Benzyl)-2H-Indazole-6-Carboxylic Acid;2-(5-Bromo-2-Cyclopentylmethoxy-Benzyl)-2H-Indazole-6-Carboxylic Acid;or a pharmaceutically acceptable salt thereof.3. A compound selected from the group consisting of:1-(3-Isobutoxy-6-Methyl-Pyridin-2-Ylmethyl)-1H-Indazole-5-Carboxylic Acid;1-(5-Bromo-2-Isobutoxy-Benzyl)-1H-Pyrrolo[3,2-B]Pyridine-5-Carboxylic Acid;or a pharmaceutically acceptable salt thereof. This application is a continuation of U.S. patent application Ser. No. 16/539,835, filed Aug. 13, 2019, which is a continuation of U.S. patent application Ser. No. 15/406,295, filed Jan. 13, 2017, now U.S. Pat. No. 10,392,382, issued Aug. 27, 2019, which is a continuation of U.S. patent application Ser. No. 13/720,520, filed Dec. 19, 2012, now U.S. Pat. No. 9,567,328, issued Feb. 14, 2017, which claims the benefit of U.S. Provisional Application Serial No. 61,578,640, filed Dec. 21, 2011, the disclosures of which are hereby incorporated by reference in their entireties and serve as the basis of a priority and/or benefit claim for the present application.This invention relates to compounds, to processes for their preparation, to pharmaceutical compositions containing them and to their use in medicine, in particular their use in the ...

NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS

The present invention discloses compounds according to Formula I: 2. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris Me.6. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris H claim 1 , F claim 1 , or Cl.7. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris H claim 1 , Me claim 1 , or Et.8. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris CN claim 1 , F claim 1 , Cl claim 1 , —SOMe or —SOEt.10. A compound claim 1 , or pharmaceutically acceptable salt thereof claim 1 , according to wherein the compound is (1R claim 1 ,2R)—N-[6-[(6-cyano-4-methyl-3-pyridyl)oxy]-1-methyl-benzimidazol-4-yl]-2-fluoro-cyclopropanecarboxamide.11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , according to .12. The pharmaceutical composition according to comprising a further therapeutic agent.13. (canceled)14. A method for the treatment claim 1 , prevention or prophylaxis of allergic diseases claim 1 , inflammatory diseases claim 1 , autoimmune diseases claim 1 , proliferative diseases claim 1 , transplantation rejection claim 1 , diseases involving impairment of cartilage turnover claim 1 , congenital cartilage malformations claim 1 , and/or diseases associated with hypersecretion of IL6 or hypersecretion of interferons claim 1 , said method comprising administering an amount of a compound according to claim 1 , sufficient to effect said treatment claim 1 , prevention or prophylaxis.15. The pharmaceutical composition according to claim 12 , wherein the further therapeutic agent is an agent for the treatment of allergic diseases claim 12 , inflammatory diseases claim 12 , autoimmune diseases claim 12 , proliferative diseases claim 12 , transplantation rejection claim 12 , diseases involving impairment of cartilage ...

RING-FUSED COMPOUND

The present invention relates to a compound that has URAT1 inhibitory action, and a URAT1 inhibitor, a blood uric acid level-reducing agent and a pharmaceutical composition comprising the compound. More specifically, the present invention relates to a compound represented by Formula (I) below. 3. The compound according to claim 2 , wherein{'sup': 3', '4', '5, 'W, Wand Ware each independently a nitrogen atom, or a methine group that may have a substituent selected from the group consisting of a halogen atom and a lower alkyl group, or a pharmaceutically acceptable salt or ester of the compound.'}4. The compound according to claim 3 , wherein{'sup': 'X', 'X is a single bond, an oxygen atom, a carbonyl group, a vinylene group or a group represented by the general formula: —N(R)—, or a pharmaceutically acceptable salt or ester of the compound.'}5. The compound according to claim 4 , wherein{'sup': 1', '1', '1, 'Ris a group represented by a general formula -Q-A, or a pharmaceutically acceptable salt or ester of the compound.'}6. The compound according to claim 5 , wherein{'sup': '1', 'Qis a single bond or a lower alkylene group that may be substituted with a lower alkyl group, or a pharmaceutically acceptable salt or ester of the compound.'}7. The compound according to claim 6 , wherein{'sup': Yi', 'Yi′', 'Yi', 'Yi′', 'Y1', 'Y1′', 'Y1', 'Y1′', 'Y2', 'Y2′', 'Y1', 'Y1′', 'Y2', 'Y2′', 'Y3', 'Y3′', 'Y1', 'Y1′', 'Y2', 'Y2′', 'Y3', 'Y3′', 'Y4', 'Y4′', 'Y1', 'Y1′', 'Y2', 'Y2′', 'Y3', 'Y3′', 'Y4', 'Y4′', 'Y5', 'Y5′', 'Y1', 'Y1′', 'Y2', 'Y2′', 'Y3', 'Y3′', 'Y4', 'Y4′', 'Y5', 'Y5′', 'Y6', 'Y6′', 'Y1', 'Y1′', 'Y2', 'Y2′', 'Y3', 'Y3′', 'Y4', 'Y4′', 'Y5', 'Y5′', 'Y6', 'Y6′, 'sub': n', 'n, 'Y is a single bond or (CRR)(herein n is any integer of 1 to 6, i is any integer of 1 to n, and (CRR)represents (CRR) when n=1; represents (CRR)—(CRR) when n=2; represents (CRR)—(CRR)—(CRR) when n=3; represents (CRR)—(CRR)—(CRR)—(CRR) when n=4; represents (CRR)—(CRR)—(CRR)—(CRR)—(CRR) when n=5; and ...

AMINOQUINAZOLINE COMPOUNDS HAVING ANTI-INFLAMMATORY, ANTIFUNGAL, ANTIPARASITIC, AND ANTICANCER ACTIVITY

Amine compounds having activity against inflammation, fungi, unicellular parasitic microorganisms, and cancer are described. The compounds contain a monocyclic, bicyclic, or tricyclic aromatic ring having one, two, or three ring nitrogen atoms. 2. The compound or salt of claim 1 , wherein Q is absent.3. The compound or salt of claim 2 , wherein the compound is selected from the group consisting of:N-(Decyl)quinazolin-4-amine,N-Dodecylquinazolin-4-amine,N-Decyl-7-fluoroquinazolin-4-amine,N-Dodecyl-7-fluoroquinazolin-4-amine,7-Chloro-N-decylquinazolin-4-amine,7-Chloro-N-dodecylquinazolin-4-amine.4. The compound or salt of claim 1 , wherein Q is O or NHC(O).5. The compound or salt of claim 4 , wherein the compound is selected from the group consisting of:N-(6-Butoxyhexyl)quinazolin-4-amine,N-[8-(Hexyloxy)octyl]quinazolin-4-amine,N-[8-(4-Methoxyphenoxy)octyl]quinazolin-4-amine,N-{2-[2-(Hexyloxy)phenoxy]ethyl}quinazolin-4-amine,N-{3-[2- (Hexyloxy)phenoxy]propyl}quinazolin-4-amine,N-{4-[2-(Hexyloxy)phenoxy]butyl}quinazolin-4-amine,N-[8-(Quinazolin-4-ylamino)octyl]nicotinamide.6. The compound or salt of claim 1 , wherein n is 1 claim 1 , Q is absent claim 1 , and Ris phenyl substituted by alkoxy having from 1 to 10 carbon atoms or phenoxy.7. The compound or salt of claim 6 , wherein the compound is selected from the group consisting of:N-[3-(Hexyloxy)benzyl]quinazolin-4-amine,N-[3-(Decyloxy)benzyl]quinazolin- 4-amine,N-(3 -Phenoxybenzyl)quinazolin-4-amine,N-[4-(Decyloxy)benzyl]quinazolin-4-amine,N-[4-(Hexyloxy)benzyl]quinazolin-4-amine.8. A compound claim 6 , N-(Decyl)quinazolin-4-amine or a pharmaceutically acceptable salt thereof.9. A pharmaceutical composition comprising an effective amount of the compound or pharmaceutically acceptable salt of and a pharmaceutically acceptable carrier.10. A method for treating or preventing a condition in a mammalian subject; the condition being selected from the group consisting of an inflammatory disease claim 1 , a fungal infection ...

COMPOUNDS FOR TREATING DENGUE VIRUS INFECTIONS AND OTHER INFECTIONS

Provided herein are compounds, pharmaceutical compositions, methods, and kits for treating viral infections (e.g., Dengue viral infections). In certain embodiments, compounds useful in the methods described herein are of Formula (I) or (II). 2. The method of claim 1 , wherein the compound is of Formula (I) claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , hydrate claim 1 , polymorph claim 1 , co-crystal claim 1 , tautomer claim 1 , stereoisomer claim 1 , isotopically labeled derivative claim 1 , or prodrug thereof.23. The method of or claim 1 , wherein Ring A is optionally substituted phenyl.28. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Z is —NR—.29. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Z is —OC(═O)—.30. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Z is —NRC(═O)—.31. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Z is —NRS(═O)—.32. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Y is —O—.33. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Y is —C(R)—.34. The method of claim 33 , wherein Y is —C(CN)H—.35. The method of any one of - claim 33 , claim 33 , claim 33 , claim 33 , and - claim 33 , wherein Xis —Cl.36. The method of any one of - claim 33 , claim 33 , claim 33 , claim 33 , and - claim 33 , wherein Xis hydrogen.37. The method of any one of - claim 33 , claim 33 , claim 33 , claim 33 , and - claim 33 , wherein Xis optionally substituted Calkyl.38. The method of claim 37 , wherein Xis unsubstituted Calkyl.39. The method of or claim 37 , wherein Xis methyl.40. The method of any one of claim 37 , claim 37 , claim 37 , and - claim 37 , ...

STORE OVERLOAD-INDUCED CALCIUM RELEASE INHIBITORS AND METHODS FOR PRODUCING AND USING THE SAME

The present invention provides compounds having store overload-induced Ca release (SOICR) inhibitory activity and methods for producing and using the same. In particular, compounds of the invention is of the formula: R—X-L-X—R, wherein R, X, L, X, and Rare those defined herein. 2. The compound according to claim 1 , wherein Ris selected from the group consisting of carbazol-2-yl; carbazol-3-yl; carbazol-4-yl; 2 claim 1 ,3 claim 1 ,4 claim 1 ,9-tetrahydro-1H-carbazol-6-yl; 9H-fluoren-4-yl; 9H-fluoren-9-on-4-yl; dibenzo[b claim 1 ,d]furan-2-yl; (phenylamino)phenyl; 10H-phenothiazin-2-yl; naphthalenyl; adamantanyl; (adamantanyl)alkyl; N-acyl-9H-cabazol-4-yl; 10H-5 claim 1 ,5-dioxide-phenothiazin-2-yl; 2-oxo-1 claim 1 ,2 claim 1 ,3 claim 1 ,4 claim 1 ,4a claim 1 ,8a-hexahydroquinolin-6-yl; 1H-indol-5-yl claim 1 , and 1H-indazol-6-yl claim 1 , each of which is optionally substituted;3. The compound according to claim 1 , wherein Xis O or NH.7. The compound according to claim 1 , wherein Ris selected from the group consisting of phenyl claim 1 , benzyl claim 1 , pyrid-2-yl claim 1 , benzo[d]oxazol-2-yl claim 1 , and benzofuran-2-yl claim 1 , each of which is optionally substituted.8. The compound according to claim 1 , wherein said compound is any one of the compounds in Tables 1-9.9. A method of treating cardiac arrhythmia in a heart failure patient claim 1 , said method comprising administering to a heart failure patient a therapeutically effective amount of a compound of to treat cardiac arrhythmia.10. The method of claim 1 , wherein said compound of inhibits store-overload-induced calcium release (SOICR).11. The method of claim 1 , wherein SOICR inhibition of the compound of is achieved by regulating calcium efflux through the RyR2 channel.12. The method of claim 9 , wherein calcium ion-induced calcium ion release (CICR) is minimally inhibited or not inhibited.13. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or ...

2-ARYL- AND 2-ARYLALKYL-BENZIMIDAZOLES AS MIDH1 INHIBITORS

The present invention relates to 2-Aryl- and 2-Arylalkyl-benzimidazoles of general formula (I): in which A, R, R, R, R, R, R, R, Rand Rare as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients. 2. The compound according to claim 1 , wherein:{'sub': 2', '2', '2, 'claim-text': and', {'sup': '5', 'Rrepresents a group selected from, {'sup': 12', '12', '12, 'sub': 1', '6', '1', '6', '2', '6', '2', '6, '—C(O)OH, —C(═O)OR, HOC(═O)—(C-C-alkyl)-, ROC(═O)—(C-C-alkyl)-, HOC(═O)—(C-C-alkenyl)-, ROC(═O)—(C-C-alkenyl)-,'}, {'sub': 1', '6', '1', '6, 'sup': '12', 'HOC(═O)—(C-C-alkoxy)-, ROC(═O)—(C-C-alkoxy)- and cyano;'}], 'A represents a bond or a —CH— or a —(CH)— group,'}or{'sub': 3', '3', '2, 'claim-text': and', {'sup': '5', 'Rrepresents a group selected from, {'sub': 1', '6', '1', '6', '2', '6', '2', '6', '1', '6', '1', '6, 'sup': 12', '12', '12, '—C(═O)OH, HOC(═O)—(C-C-alkyl)-, ROC(═O)—(C-C-alkyl)-, HOC(═O)—(C-C-alkenyl)-, ROC(═O)—(C-C-alkenyl)-, HOC(═O)—(C-C-alkoxy)-, ROC(═O)—(C-C-alkoxy)- and cyano;'}], 'A represents a —CH(CH)— or a —C(CH)— group,'}{'sup': '1', 'claim-text': [{'sub': 1', '6', '3', '6', '1', '6', '3', '6', '1', '6', '1', '6, 'which phenyl group is optionally substituted with one, two or three substituents, which are, independently of each other, a halogen atom or a group selected from: C-C-alkyl, C-C-cycloalkyl, C-C-alkoxy, C-C-cycloalkyloxy, C-C-haloalkyl, C-C-haloalkoxy and cyano;'}, 'and', {'sub': 1', '3, 'which heteroaryl group is optionally substituted with one, two or three substituents, which are, independently of each other, a halogen atom or a group selected from: C-C-alkyl and phenyl;'}]}, ' ...

SUBSTITUTED BENZIMIDAZOLES

The present invention relates to substituted benzimidazole compounds of general formula (I) in which R, Rand A are as defined in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients. 2. A compound according to claim 1 , wherein:{'sup': 4a', '4d, 'Rand Rrepresent hydrogen;'}{'sup': 4b', '4c, 'sub': 1', '6', '1', '6', '1', '6', '1', '6, 'Rand Rare selected, independently from each other, from hydrogen, halogen, —CN, C-C-alkyl-, C-C-alkoxy-, halo-C-C-alkyl-, or halo-C-C-alkoxy-;'}or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.4. A compound according to claim 1 , wherein:{'sup': '3', 'claim-text': {'sup': '7', 'said aryl-, heteroaryl-, aryl-X— or heteroaryl-X— group being optionally substituted, identically or differently, with 1, 2 or 3 Rgroups;'}, 'Rrepresents a hydrogen atom or a halogen atom or an aryl-, heteroaryl-, aryl-X— or heteroaryl-X— group;'}or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.5. A compound according to claim 1 , wherein:{'sup': 7', '6a', '6', '6', '6, 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '5', '2, 'Rrepresents a halogen atom, or a HO—, —CN, C-C-alkoxy-, halo-C-C-alkoxy-, C-C-alkyl-, HO—C-C-alkyl-, 3- to 7-membered heterocycloalkyl-, heteroaryl-, —C(═O)N(H)R, —OR, —SR, —SFor —S(═O)Rgroup;'}or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.6. A compound according to claim 1 , wherein:{'sup': '5', 'sub': 1', '6', '2', 'm', '1', '6, 'claim-text': {'sub': 1', '6', '2', 'm', '1', '6, 'sup': '8', 'said C-C-alkyl-, —(CH)-(3- to 7-membered ...

FTO Inhibitors

The invention provides compounds that inhibit FTO (fat mass and obesity), including pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof, particularly obesity, with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition. 2. The pharmaceutical composition of claim 1 , wherein the heterocyclic C3-C18 hydrocarbyl comprises:a 3 membered ring that is an optionally substituted: aziridine, oxirane, oxaziridine;a 4 membered ring that is an optionally substituted: azetidine, oxetane, oxazetidine;a 5 membered ring that is an optionally substituted: pyrrole, 1, 2-diazole (pyrazole), 1, 3 diazole (imidazole), thiazole, isothiazole, oxazole, isoxazole, furan, dioxole, thiophene;a 6 membered ring that is an optionally substituted: pyridine, diazine, triazine, oxazine, thiazine, dioxine, oxathiine, dithiine;a 9 membered ring that is an optionally substituted: indole, benzothiazole, benzooxazole, benzofuran, benzodioxole, benzothiophene, benzodithiole; ora 10 membered ring that is an optionally substituted: quinoline, quinoxaline, quinazoline, chromene, benzodioxine, thiochromene, benzodithiine.4. The pharmaceutical composition of claim 1 , copackaged or coformulated with a second claim 1 , different medicament for inhibiting weight gain claim 1 , promoting weight loss claim 1 , reducing serum LDL claim 1 , cholesterol claim 1 , LDL-c claim 1 , or triglycerides claim 1 , or treating obesity or an obesity related disease or Alzheimer's disease.5. A method comprising administering to a person in need thereof a composition of to inhibit weight gain claim 1 , promote weight loss claim 1 , reduce serum LDL claim 1 , cholesterol claim 1 , LDL-c claim 1 , or triglycerides claim 1 , or treat obesity or an obesity related disease or Alzheimer's disease.6. The method of ...

Organic electroluminescence device

According to the present invention, there is provided an organic electroluminescent device which has an anode, a hole transport layer, a luminous layer, an electron transport layer, and a cathode arranged in order of description. The device is characterized in that: the hole transport layer includes a specific arylamine compound, and that the luminous layer includes a specific indenoindole derivative or a specific carbazole derivative. The organic EL device of the present invention has improved efficiency of hole transport from the hole transport layer to the luminous layer and also improved efficiency of electron transport from the electron transport layer to the luminous layer, in comparison to conventional organic EL devices.

KYNURENINE-3-MONOOXYGENASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF

Certain compounds, or pharmaceutically acceptable salts or prodrugs thereof, are provided herein. Also provided are pharmaceutical compositions comprising at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein as a single active agent or administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity. 121.-. (canceled)23. The method of claim 22 , wherein said condition or disorder is a neurodegenerative disease.24. The method of claim 22 , wherein said condition or disorder is Huntington's Disease.25. The method of claim 22 , wherein said condition or disorder is a polyglutamine disorder claim 22 , a spinocerebellar ataxias neurodegenerative disease claim 22 , a psychiatric of neurological disease or disorder claim 22 , Alzheimer's disease claim 22 , Parkinson's disease claim 22 , amyotropic lateral sclerosis claim 22 , Creutzfeld-Jacob disease claim 22 , trauma-induced neurodegeneration claim 22 , high-pressure neurological syndrome claim 22 , dystonia claim 22 , olivopontocerebellar atrophy claim 22 , amyotrophic lateral sclerosis claim 22 , multiple sclerosis claim 22 , epilepsy claim 22 ...