AR045445A1 - Compuestos ihinibidores de canales ionicos regulados por voltaje - Google Patents

Compuestos ihinibidores de canales ionicos regulados por voltaje

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Publication number
AR045445A1
AR045445A1 ARP040102793A ARP040102793A AR045445A1 AR 045445 A1 AR045445 A1 AR 045445A1 AR P040102793 A ARP040102793 A AR P040102793A AR P040102793 A ARP040102793 A AR P040102793A AR 045445 A1 AR045445 A1 AR 045445A1
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AR
Argentina
Prior art keywords
ring
chr4
hydrogen
unsubstituted phenyl
optionally substituted
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ARP040102793A
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English (en)
Inventor
Dean Mitchell Wilson
Andreas Peter Termin
Thimothy Neubert
Jian Wang
Yulian Zhang
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Vertex Pharma
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Publication of AR045445A1 publication Critical patent/AR045445A1/es

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Abstract

La presente se refiere para el tratamiento de dolor agudo, crónico, neuropático o inflamatorio, artritis, migraña, cefaleas acuminadas, neuralgia del trigémino, neuralgia herpética, neuralgia generales, epilepsia, trastornos neurodegenerativos, ansiedad, depresión, miotonia, ataxia, esclerosis múltiple. Reivindicación 1: Un compuesto de la fórmula (1), o una de sus sales farmacéuticamente aceptables, en donde: p es 0, 1 ó 2; X1, X2, X3 y X4 se seleccionan, cada uno de modo independiente, de NR3, C=O, CHR4, S, O, S=O o SO2; R1 y R2 son cada uno, de modo independiente, hidrógeno o un grupo opcionalmente sustituido seleccionado de alifático C16, un anillo arilo de 5-6 miembros que tiene 0-5 heteroátomos seleccionados de modo independiente de nitrógeno, oxígeno o azufre o un anillo saturado o parcialmente insaturado de 3-7 miembros que tiene 0-3 heteroátomos seleccionados de modo independiente de nitrógeno, oxígeno o azufre; o R1 y R2 forman, junto con el átomo de nitrógeno al que están unidos, un anillo heterociclilo o heteroarilo opcionalmente sustituido de 3-8 miembros que tiene 1-3 heteroátomos seleccionados de modo independiente de nitrógeno, oxígeno o azufre, en donde R1, R2 o cualquier anillo formado por R1 y R2 tomados juntos están opcionalmente sustituidos cada uno, de modo independiente, en uno o varios átomos de carbono con 0-4 apariciones de -R5 y en uno o varios átomos de nitrógeno sustituibles con -R6; Anillo A es un anillo arilo monocíclico de 5-6 miembros o bicíclicos de 8-10 miembros que tiene 0-5 heteroátomos seleccionados de modo independiente de nitrógeno, oxígeno o azufre o un anillo saturado o parcialmente insaturado de 3-7 miembros que tiene 0-3 heteroátomos seleccionados de modo independiente de nitrógeno, oxígeno o azufre, opcionalmente sustituidos en uno o varios átomos de carbono con 0-5 apariciones de -R7 y en uno o varios átomos de nitrógeno sustituibles con -R8; cada aparición de R4, R5 y R7 es, de modo independiente, Q-Rx; en donde Q es un enlace o es una cadena de alquilideno C1-6, en donde hasta dos unidades de metileno no adyacentes de Q están opcional e independientemente reemplazados por CO, CO2, COCO, CNR, OCONR, NRNR, NRNRCO, NRCO, NRCO2, NRCONR, SO, SO2, NRSO2, SO2NR, NRSO2NR, O, S o NR; cada aparición de Rx se selecciona de modo independiente de R', halógeno, NO2 o CN; cada aparición de R se selecciona del modo independiente de hidrógeno o un grupo alifático C1-6 opcionalmente sustituido; cada aparición de R' se selecciona de modo independiente de hidrógeno o un grupo opcionalmente sustituido seleccionado de alifático C1-8, arilo C6-10, un anillo heteroarilo que tiene 5-10 átomos de anillo o un anillo heterociclilo que tiene 3-10 átomos de anillo o en donde R y R' tomados junto con los átomos a los que están unidos o dos apariciones de R' tomadas junto con los átomos a los que están unidas, forman un anillo cicloalquilo, heterociclilo, arilo o heteroarilo de 5-8 miembros que tiene 0-3 heteroátomos seleccionados de modo independiente de nitrógeno, oxígeno o azufre; y cada aparición de R3, R6 o R8 es, de modo independiente, R', -COR', -CO2(alifático C1-6), -CON(R')2 o -SO2R'; con la condición de que: a) R1 no sea hidrógeno cuando R2 es indazol-3-ilo opcionalmente sustituido; b) R1 no sea hidrógeno cuando R2 es pirazol-3-ilo opcionalmente sustituido; c) R1 no sea hidrógeno cuando R2 es 1,2,4-triazol-3-ilo; d) cuando p es 1, entonces: i) cuando R1 y R2, tomados con el átomo de nitrógeno, es N-morfolino y Anillo A es fenilo insustituido, entonces X1, X2, X3, y X4 no sean, respectivamente: a) CH2, CH(CH2)Ph, NR3 y CHCH3; b) CH2, CH2, CH2 y S; c) CH2, S, CH2 y S; d) CH2, CH2, S y CH2; e) CH2, CHMe, S y CH2; o f) CHMe, CH2, N(CH2)Ph y CH2; ii) R1 no sea hidrógeno y R2 no sea CH2Ph, (CH2)2O(CH2)2OH o -CH2(1,3-benzodioxol-5-il) cuando el Anillo A es imidazol-1-ilo; iii) cuando R1 y R2, tomados junto con el átomo de nitrógeno, es N-piperidinilo, entonces: a) cuando X1, X2 y X3 son CH2 Y CH4 es S, entonces el Anillo A no sea fenilo insustituido; y b) cuando X1, X2 y X4 son CH2; y X3 es S, entonces el Anillo A no sea fenilo insustituido; iv) cuando R1 y R2, tomados junto con el átomo de nitrógeno, es N-piperizinilo, X1, X2 y X3 son CH2, y X4 es S, entonces el Anillo A no sea 3-NO2Ph, 4-piridinilo o fenilo insustituido; v) cuando uno de X1, X2, X3 o X4 es NR3 y los otros de X1, X2, X3 o X4 son cada uno CH2 y R1 y R2 son cada uno Me, H, CH2Ph o (CH2)2NMe2, entonces el Anillo A no sea pirid-2-ilo sustituido en la posición (6); vi) cuando X1, X2 y X3 son cada uno CH2, X4 es S, R1 es H y R2 es -CH-C:::CH, entonces el Anillo A no sea fenilo insustituido; vii) cuando X1 es NMe; X2, X3 y X4 son cada uno CH2, R1 es H y R2 es fenilo insustituido, entonces el Anillo A no sea fenilo insustituido; y viii) cuando X1, X2 y X4 son cada uno CH2, X3 es S, R1 y R2 son cada uno Me, entonces el Anillo A no sea fenilo insustituido; y e) cuando o es 0, entonces: i) cuando X1 es CH2, X2 es NR3, X3 es C=O; o X1 es C=O, X2 es ChR4 y X3 es NR3; o X2 es NR3, X2 es C=O, y X3 es CHR4; o X1 es CH2, X2 es O y X3 es C=O, entonces cuando R1 es hidrógeno y R2 es fenilo insustituido o -CH2CH2Cl o cuando R1 y R2, tomados juntos forman piperazinilo, morfolino, piperidinilo o pirrolidinilo opcionalmente sustituido, entonces el Anillo A no es piperidinilo, piperazinilo, morfolino o pirrolidinilo opcionalmente sustituido; ii) cuando X1 es CHR4, X2 es SO2 y X3 es CHR4 y R1 y R2, tomados juntos son piperazinilo, entonces el Anillo A no sea fenilo insustituido; iii) cuando X1 y X2 son CHR2, X3 es O, R1 es hidrógeno y R2 es - C(=O)CH3, entonces el Anillo A no sea furilo sustituido; iv) cuando X1 es S, X2 es CHR4, X3 es CHR4; o X1 es CHR4, X2 es S y X3 es CHR4; o X1 y X2 son CHR4 y X3 es S, entonces el Anillo A no sea morfolino, pirrolidinilo, piperazinilo, piperidinilo ligado con N opcionalmente sustituido o no sea fenilo insustituido o ciclopropilo; v) cuando X1 es CHR4, X2 es NR3, X3 es CHR4 y R1 y R2 son ambos metilo, entonces el Anillo A no sea 6-metil-2-piridilo; vi) cuando X1 es NR3, X2 es C=O, X2 es NR3 y R1 y R2 son ambos metilo, entonces el Anillo A no sea fenilo insustituido; y vii) cuando X1 y X2 son CHR4, X3 es NR3, R1 es hidrógeno y R2 es fenilo insustituido, entonces el Anillo A no sea fenilo insustituido; y además, con la condición de que: a) cuando cada uno de X1, X2, X3 y X4 es CHR4 y p es 0 ó 1, entonces al menos un r4 sea distinto de hidrógeno; b) cuando cada uno de X1, X2, X3 y X4 es CHR4 y el Anillo A es un grupo piperizinilo sustituido o insustituido, entonces al menos un R4 sea distinto de hidrógeno; c) cuando cada uno de X1, X2, X3 y X4 es CHR4, R1 es hidrógeno y R2 es 1H-indazol-3-ilo, 7-fluoro-1H-indazol-3-ilo, 5-fluoro-1H-indazol-3-ilo, 5,7-difluoro-1H-indazol-3-ilo o 5-metil-1H-pirazolilo y el Anillo A es un grupo fenilo insustituido o es un grupo fenilo sustituido en la posición orto con Cl o CF3, entonces al menos un R4 sea distinto de hidrógeno; y d) 5(6H)-quinazolinona, 4-anilino-7,8-dihidro-2,7-difenil- y 5(6H)-quinazolinona, 4-anilino-7,8-dihidro-7,7- dimetil-2-fenil- quedan excluidos.
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Families Citing this family (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2271958T3 (es) * 1996-09-04 2007-04-16 Intertrust Technologies Corp Sistemas, procedimientos y tecnicas fiables de soporte de infraestructuras para comercio electronico seguro, transacciones electronicas, control y automatizacion de procedimientos comerciales, informatica distribuida y gestion de derechos.
US7235551B2 (en) * 2000-03-02 2007-06-26 Smithkline Beecham Corporation 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases
MXPA03003612A (es) * 2000-10-23 2003-06-19 Smithkline Beecham Corp Compuestos novedosos.
BR0309053A (pt) * 2002-04-19 2005-02-22 Smithkline Beecham Corp Compostos
US7968545B2 (en) * 2003-08-05 2011-06-28 Vertex Pharmaceuticals Inc. Compositions useful as inhibitors of voltage-gated ion channels
JP4862654B2 (ja) * 2004-10-08 2012-01-25 アステラス製薬株式会社 芳香環縮合ピリミジン誘導体
TW200621257A (en) * 2004-10-20 2006-07-01 Astellas Pharma Inc Pyrimidine derivative fused with nonaromatic ring
US20060128710A1 (en) * 2004-12-09 2006-06-15 Chih-Hung Lee Antagonists to the vanilloid receptor subtype 1 (VR1) and uses thereof
ES2359931T3 (es) * 2005-03-11 2011-05-30 Merck Patent Gmbh Tetrahidro- y dihidroquinazolinonas.
US7402596B2 (en) 2005-03-24 2008-07-22 Renovis, Inc. Bicycloheteroaryl compounds as P2X7 modulators and uses thereof
AR053450A1 (es) 2005-03-25 2007-05-09 Glaxo Group Ltd Derivados de 3,4-dihidro-pirimido(4,5-d)pirimidin-2-(1h)-ona 1,5,7 trisustituidos como inhibidores de la quinasa p38
CN101495475A (zh) * 2005-03-25 2009-07-29 葛兰素集团有限公司 制备吡啶并[2,3-d]嘧啶-7-酮和3,4-二氢嘧啶并[4,5-d]嘧啶-2(1H)-酮衍生物的方法
US7423042B2 (en) 2005-03-25 2008-09-09 Glaxo Group Limited Compounds
PE20100737A1 (es) 2005-03-25 2010-11-27 Glaxo Group Ltd Nuevos compuestos
CA2606760C (en) * 2005-05-04 2014-12-23 Renovis, Inc. Tetrahydronaphthyridine and tetrahydropyrido[4,3-d]pyrimidine compounds and compositions thereof useful in the treatment of conditions associated with neurological and inflammatory disorders and disfunctions
EP1904491A2 (en) 2005-05-31 2008-04-02 Vertex Pharmaceuticals Incorporated Heterocycles useful as modulators of ion channels
US7718641B2 (en) 2005-11-23 2010-05-18 Aros Pharma Aps Pyrrolo [3,4-H] isoquinoline compounds and methods for modulating gated ion channels
PE20080145A1 (es) 2006-03-21 2008-02-11 Janssen Pharmaceutica Nv Tetrahidro-pirimidoazepinas como moduladores de trpv1
WO2007117465A2 (en) 2006-03-31 2007-10-18 Abbott Laboratories Indazole compounds
WO2007115409A1 (en) * 2006-04-10 2007-10-18 Painceptor Pharma Corporation Compositions and methods for modulating gated ion channels
GB0608820D0 (en) 2006-05-04 2006-06-14 Piramed Ltd Pharmaceutical compounds
CN101500575A (zh) * 2006-06-12 2009-08-05 沃泰克斯药物股份有限公司 可用作离子通道调控剂的噻吩并嘧啶
EP2044086A2 (en) * 2006-06-30 2009-04-08 Janssen Pharmaceutica N.V. Thiazolopyrimidine modulators of trpv1
JP5231411B2 (ja) 2006-07-06 2013-07-10 アレイ バイオファーマ、インコーポレイテッド Ａｋｔプロテインキナーゼ阻害剤としてのジヒドロチエノピリミジン
US8063050B2 (en) 2006-07-06 2011-11-22 Array Biopharma Inc. Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors
US8329701B2 (en) 2006-07-06 2012-12-11 Array Biopharma Inc. Dihydrofuro pyrimidines as AKT protein kinase inhibitors
KR101527232B1 (ko) 2006-07-06 2015-06-09 어레이 바이오파마 인크. Ａｋｔ 단백질 키나제 억제제로서의 시클로펜타〔ｄ〕피리미딘
CA2687764A1 (en) * 2007-05-25 2008-12-04 Vertex Pharmaceuticals Incorporated Ion channel modulators and methods of use
EP2404907B1 (en) 2007-07-05 2015-01-14 Array Biopharma, Inc. Pyrimidyl cyclopentanes as AKT protein kinase inhibitors
ES2551352T3 (es) 2007-07-05 2015-11-18 Array Biopharma, Inc. Pirimido ciclopentanos útiles para el tratamiento de enfermedades inflamatorias o hiperproliferativas
US8846683B2 (en) 2007-07-05 2014-09-30 Array Biopharma, Inc. Pyrimidyl cyclopentanes as Akt protein kinase inhibitors
US9409886B2 (en) 2007-07-05 2016-08-09 Array Biopharma Inc. Pyrimidyl cyclopentanes as AKT protein kinase inhibitors
EP2224929B1 (en) 2007-12-17 2016-05-04 Janssen Pharmaceutica, N.V. Imidazolo-, oxazolo-, and thiazolopyrimidine modulators of trpv1
CN101959887B (zh) 2008-01-08 2013-07-31 阵列生物制药公司 作为激酶抑制剂的吡咯并吡啶
WO2009089359A1 (en) 2008-01-09 2009-07-16 Array Biopharma Inc. Pyrazolopyridines as kinase inhibitors
CN101932564B (zh) 2008-01-09 2012-12-26 阵列生物制药公司 作为akt蛋白激酶抑制剂的羟基化嘧啶基环戊烷类
JP5539225B2 (ja) 2008-01-09 2014-07-02 アレイ バイオファーマ、インコーポレイテッド Ａｋｔタンパク質キナーゼ阻害剤としての水酸化されたピリミジルシクロペンタン
GB0813144D0 (en) 2008-07-17 2008-08-27 Glaxo Group Ltd Novel compounds
RU2473549C2 (ru) * 2008-07-31 2013-01-27 Дженентек, Инк. Пиримидиновые соединения, композиции и способы применения
SG176959A1 (en) * 2009-06-24 2012-01-30 Genentech Inc Oxo-heterocycle fused pyrimidine compounds, compositions and methods of use
AU2010276537B2 (en) 2009-07-27 2015-04-16 Gilead Sciences, Inc. Fused heterocyclic compounds as ion channel modulators
MX2012005463A (es) * 2009-11-12 2012-09-12 Hoffmann La Roche Compuestos de purina n/9 sustituida, composiciones y metodos de uso.
RU2515541C2 (ru) * 2009-11-12 2014-05-10 Ф.Хоффманн-Ля Рош Аг N-7 замещенные пурины и пиразолопиримидины, их композиции и способы применения
CA2802288C (en) 2010-07-02 2018-08-21 Gilead Sciences, Inc. Triazolopyridinone compounds as ion channel modulators
CN105859735B (zh) 2010-12-16 2018-03-09 霍夫曼-拉罗奇有限公司 三环pi3k抑制剂化合物和使用方法
CN103492575A (zh) 2011-01-18 2014-01-01 安姆根有限公司 NaV1.7敲除小鼠及其用途
WO2012099581A1 (en) 2011-01-19 2012-07-26 Takeda Pharmaceutical Company Limited Dihydrofuropyrimidine compounds
JP2014509859A (ja) 2011-03-16 2014-04-24 アムジエン・インコーポレーテツド １７ｎａｖ１．３およびｎａｖ１．７の強力かつ選択的阻害剤
TR201815685T4 (tr) 2011-04-01 2018-11-21 Genentech Inc Kanser tedavisi için akt ve mek inhibe edici bileşiklerin kombinasyonları.
ES2620644T3 (es) 2011-04-01 2017-06-29 Genentech, Inc. Combinaciones de compuestos inhibidores de AKT y agentes quimioterapéuticos, y métodos de uso
PL2707361T3 (pl) 2011-05-10 2018-01-31 Gilead Sciences Inc Skondensowane związki heterocykliczne stosowane jako modulatory kanału sodowego
UY34171A (es) 2011-07-01 2013-01-31 Gilead Sciences Inc Compuestos heterocíclicos fusionados como moduladores del canal iónico
NO3175985T3 (es) 2011-07-01 2018-04-28
US8846656B2 (en) * 2011-07-22 2014-09-30 Novartis Ag Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
US9944634B2 (en) * 2012-10-31 2018-04-17 Raqualia Pharma Inc. Pyrazolopyridine derivatives as TTX-S blockers
AR096927A1 (es) 2013-03-12 2016-02-10 Amgen Inc INHIBIDORES POTENTES Y SELECTIVOS DE NaV1.7
US10344060B2 (en) 2013-03-12 2019-07-09 Amgen Inc. Potent and selective inhibitors of Nav1.7
TW201512189A (zh) 2013-04-16 2015-04-01 Gruenenthal Chemie 新型被取代之嘧啶縮合化合物
WO2015006280A1 (en) * 2013-07-10 2015-01-15 Vertex Pharmaceuticals Incorporated Fused piperidine amides as modulators of ion channels
ES2819867T3 (es) * 2014-01-20 2021-04-19 Cleave Biosciences Inc Pirimidinas condensadas como inhibidores del complejo p97
AU2015214366B2 (en) * 2014-02-06 2019-04-18 Abbvie, Inc. 6-heteroaryloxy- and 6-aryloxy-quinoline-2-carboxamides and uses thereof
JP6742331B2 (ja) * 2015-03-02 2020-08-19 アムジエン・インコーポレーテツド 二環式ケトンスルホンアミド化合物
US10435645B2 (en) * 2016-12-20 2019-10-08 International Flavors & Fragrances Inc. Organoleptic compounds
JP2021535213A (ja) * 2018-08-24 2021-12-16 ジャガー セラピューティクス ピーティーイーリミテッド ＡｈＲモジュレーターとしてのテトラヒドロピリドピリミジン誘導体
KR20220153595A (ko) * 2020-02-26 2022-11-18 재규어 테라퓨틱스 피티이 리미티드 AhR 신호전달의 조절에 유용한 피리도피리미딘 유도체
AU2021263818A1 (en) 2020-04-28 2022-11-03 Global Blood Therapeutics, Inc. Cycloalkyl pyrimidines as ferroportin inhibitors
US20240101632A1 (en) * 2021-01-27 2024-03-28 Sri International Genetically engineered electrically-stimulated effector cells for in situ synthesis of proteins
CN113880859B (zh) * 2021-11-16 2022-06-21 江西科技师范大学 2-芳基-4-芳甲胺基嘧啶类化合物及其应用

Family Cites Families (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2450E (fr) * 1903-02-09 1904-04-07 Sulzer Freres Soc Palier pour pompes et autres machines analogues
DE1197466B (de) 1962-03-22 1965-07-29 Thomae Gmbh Dr K Verfahren zur Herstellung von neuen 5, 6, 7, 8-Tetrahydropyrido-[4, 3-d]pyrimidinen
DE1470336A1 (de) 1962-07-04 1969-03-20 Thomae Gmbh Dr K Neue Dihydrothieno-[3,4-d]-pyrimidine und Verfahren zu ihrer Herstellung
DE1251765B (de) * 1963-07-23 1967-10-12 Dr Karl Thomae Gesellschaft mit beschrankter Haftung Biberach/Riß Verfahren zur Herstellung von neuen 5H - Dihydrothiopyrano [4 3 d] pynmidinen
US3346452A (en) * 1963-08-19 1967-10-10 Ciba Geigy Corp 5, 6-lower alkylene-pyrimidines
FR1455810A (fr) 1963-12-16 1966-05-20 Thomae Gmbh Dr K Procédé pour fabriquer des nouvelles 4-h-m-dithiino [5, 4-d] pyrimidines
DE1470354A1 (de) * 1963-12-16 1969-10-09 Thomae Gmbh Dr K Neue 4H-m-Dithiino[5,4-d]-pyrimidine und Verfahren zu ihrer Herstellung
GB1152883A (en) * 1967-01-25 1969-05-21 Ucb Sa 4,5-Polymethylene-Pyrimidine Derivatives
FR2190818B1 (es) * 1972-06-28 1975-03-07 Roussel Uclaf
EP0022481A1 (en) 1979-06-21 1981-01-21 Mitsubishi Yuka Pharmaceutical Co., Ltd. 5,6-Alkylenepyrimidine derivatives, processes for preparing the same and pharmaceutical compositions
JPS562968A (en) * 1979-06-21 1981-01-13 Mitsubishi Yuka Yakuhin Kk Novel pyrimidine derivative
JPS60226882A (ja) * 1984-04-24 1985-11-12 Nippon Zoki Pharmaceut Co Ltd 新規ピリミドピリミジン誘導体
DE3609596A1 (de) * 1986-03-21 1987-10-01 Hoechst Ag 2-azolylmethyl-2-aryl-1,3-dioxolane und deren salze, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung
DE3888215T2 (de) 1987-01-21 1994-09-08 Merck & Co Inc Piperazinylpyrimidine als beta-adrenergische Rezeptoren blockierende Mittel.
DE3922735A1 (de) * 1989-07-11 1991-01-24 Hoechst Ag Aminopyrimidin-derivate, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als fungizide
DE4029654A1 (de) * 1990-09-19 1992-04-02 Hoechst Ag 2-phenyl-pyrimidine, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als fungizide
JPH04224580A (ja) * 1990-12-25 1992-08-13 Nippon Soda Co Ltd ピリミジン誘導体、その製造方法及び農園芸用殺菌剤
US5536725A (en) * 1993-08-25 1996-07-16 Fmc Corporation Insecticidal substituted-2,4-diamino-5,6,7,8-tetrahydroquinazolines
JPH07228573A (ja) 1994-02-16 1995-08-29 Dainippon Pharmaceut Co Ltd ２−フェニルシクロアルカノピリミジン誘導体
IL117659A (en) * 1995-04-13 2000-12-06 Dainippon Pharmaceutical Co Substituted 2-phenyl pyrimidino amino acetamide derivative process for preparing the same and a pharmaceutical composition containing same
AU2980797A (en) * 1996-06-11 1998-01-07 Yoshitomi Pharmaceutical Industries, Ltd. Fused heterocyclic compounds and medicinal uses thereof
JPH10130150A (ja) * 1996-09-05 1998-05-19 Dainippon Pharmaceut Co Ltd 酢酸アミド誘導体からなる医薬
ZA9810490B (en) * 1997-12-03 1999-05-20 Dainippon Pharmaceutical Co 2-Aryl-8-oxodihydropurine derivative process for the preparation thereof pharmaceutical composition containing the same and intermediate therefor
JPH11171865A (ja) * 1997-12-04 1999-06-29 Yoshitomi Pharmaceut Ind Ltd 縮合ヘテロ環化合物
DE19853278A1 (de) * 1998-11-19 2000-05-25 Aventis Pharma Gmbh Substituierte 4-Amino-2-aryl-cyclopenta[d]pyrimidine, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate
DE19904710A1 (de) * 1999-02-05 2000-08-10 Aventis Pharma Gmbh Substituierte 4-Amino-2-aryl-tetrahydrochinazoline, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate
MXPA03002299A (es) * 2000-09-15 2003-06-06 Vertex Pharma Compuestos de pirazol utiles como inhibidores de proteina cinasa.
EP1506196B1 (en) 2001-11-01 2012-01-18 Icagen, Inc. Pyrazolopyrimidines as sodium channel inhibitors
DE60236322D1 (de) * 2001-12-07 2010-06-17 Vertex Pharma Verbindungen auf pyrimidin-basis als gsk-3-hemmer
ATE468336T1 (de) * 2002-03-15 2010-06-15 Vertex Pharma Azolylaminoazine als proteinkinasehemmer
WO2003078426A1 (en) * 2002-03-15 2003-09-25 Vertex Pharmaceuticals, Inc. Azolylaminoazine as inhibitors of protein kinases
EP1485100B1 (en) * 2002-03-15 2010-05-05 Vertex Pharmaceuticals Incorporated Azinylaminoazoles as inhibitors of protein kinases
JP2006521398A (ja) * 2003-03-28 2006-09-21 サイオス・インコーポレーテツド ＴＧＦβの二−環式ピリミジン阻害剤
US7968545B2 (en) * 2003-08-05 2011-06-28 Vertex Pharmaceuticals Inc. Compositions useful as inhibitors of voltage-gated ion channels

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