BG64533B1 - Заместени азотсъдържащи хетероцикли като инхибитори на р38 протеинкиназа, фармацевтични състави и използването им в медицината - Google Patents
Заместени азотсъдържащи хетероцикли като инхибитори на р38 протеинкиназа, фармацевтични състави и използването им в медицината Download PDFInfo
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Classifications
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US3428896P | 1996-12-18 | 1996-12-18 | |
US08/822,373 US5945418A (en) | 1996-12-18 | 1997-03-20 | Inhibitors of p38 |
US08/862,925 US6147080A (en) | 1996-12-18 | 1997-06-10 | Inhibitors of p38 |
Publications (2)
Publication Number | Publication Date |
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BG103575A BG103575A (en) | 2000-06-30 |
BG64533B1 true BG64533B1 (bg) | 2005-06-30 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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BG103575A BG64533B1 (bg) | 1996-12-18 | 1999-07-13 | Заместени азотсъдържащи хетероцикли като инхибитори на р38 протеинкиназа, фармацевтични състави и използването им в медицината |
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US (1) | US6147080A (no) |
EP (1) | EP0951467B1 (no) |
JP (1) | JP4171072B2 (no) |
CN (2) | CN1284783C (no) |
AP (1) | AP1136A (no) |
AT (1) | ATE236165T1 (no) |
AU (1) | AU738000B2 (no) |
BG (1) | BG64533B1 (no) |
BR (1) | BR9714415A (no) |
CA (1) | CA2274825C (no) |
CZ (1) | CZ299600B6 (no) |
DE (1) | DE69720522T2 (no) |
DK (1) | DK0951467T3 (no) |
EA (1) | EA002855B1 (no) |
EE (1) | EE04191B1 (no) |
ES (1) | ES2202658T3 (no) |
HK (1) | HK1023340A1 (no) |
HU (1) | HUP0001125A3 (no) |
ID (1) | ID21919A (no) |
IL (1) | IL130349A0 (no) |
IS (1) | IS5069A (no) |
NO (1) | NO315047B1 (no) |
NZ (1) | NZ336146A (no) |
PL (1) | PL202464B1 (no) |
PT (1) | PT951467E (no) |
SK (1) | SK284578B6 (no) |
TR (1) | TR199902194T2 (no) |
TW (1) | TW521071B (no) |
WO (1) | WO1998027098A1 (no) |
Families Citing this family (126)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7091181B2 (en) | 1994-12-12 | 2006-08-15 | Omeros Corporation | Method of inhibition of pain and inflammation during surgery comprising administration of soluble TNF receptors |
WO2000023072A1 (en) * | 1998-10-20 | 2000-04-27 | Omeros Medical Systems, Inc. | Irrigation solution containing mapk inhibitors and their use for treating pain and inflammation |
US6608060B1 (en) | 1996-12-18 | 2003-08-19 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
WO1999019471A1 (en) | 1997-10-16 | 1999-04-22 | Board Of Regents, The University Of Texas System | Models and treatments for cardiac hypertrophy in relation with nf-at3 function |
US6335340B1 (en) | 1997-12-19 | 2002-01-01 | Smithkline Beecham Corporation | compounds of heteroaryl substituted imidazole, their pharmaceutical compositons and uses |
MY132496A (en) * | 1998-05-11 | 2007-10-31 | Vertex Pharma | Inhibitors of p38 |
WO1999061039A2 (en) * | 1998-05-22 | 1999-12-02 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Novel composition for modulating ischemic cell death |
US6858617B2 (en) | 1998-05-26 | 2005-02-22 | Smithkline Beecham Corporation | Substituted imidazole compounds |
EP1277740A1 (en) * | 1998-06-12 | 2003-01-22 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
EP1086085A1 (en) | 1998-06-12 | 2001-03-28 | Vertex Pharmaceuticals Incorporated | INHIBITORS OF p38 |
US6184226B1 (en) | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
AR023659A1 (es) | 1998-09-18 | 2002-09-04 | Vertex Pharma | Un compuesto inhibidor de p38, una composicion farmaceutica que lo comprende y el uso de dicha composicion en el tratamiento y prevencion de estados patologicos |
CA2337755C (en) * | 1998-09-18 | 2008-07-29 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
AU1909200A (en) | 1998-11-04 | 2000-05-22 | Smithkline Beecham Corporation | Pyridin-4-yl or pyrimidin-4-yl substituted pyrazines |
UA73492C2 (en) | 1999-01-19 | 2005-08-15 | Aromatic heterocyclic compounds as antiinflammatory agents | |
CA2360934A1 (en) | 1999-02-22 | 2000-08-31 | Lin-Hua Zhang | Polycyclo heterocyclic derivatives as antiinflammatory agents |
NZ514711A (en) | 1999-03-12 | 2004-02-27 | Boehringer Ingelheim Pharma | Compounds useful as anti-inflammatory agents |
MXPA01009077A (es) | 1999-03-12 | 2002-03-27 | Boehringer Ingelheim Pharma | Composiciones heterociclicos aromaticos como agentes anti-inflamatorios. |
JP2000281588A (ja) * | 1999-03-30 | 2000-10-10 | Sankyo Co Ltd | ガンの予防又は治療薬及びそのスクリーニング方法 |
WO2001001986A1 (en) * | 1999-07-02 | 2001-01-11 | Lipton Stuart A | Method of reducing neuronal injury or apoptosis |
ATE312823T1 (de) | 1999-07-09 | 2005-12-15 | Boehringer Ingelheim Pharma | Verfahren zur herstellung heteroarylsubstituierter ureaverbindungen |
HUP0203564A3 (en) * | 1999-10-21 | 2004-07-28 | Hoffmann La Roche | Heteroalkylamino-substituted bicyclic nitrogen heterocycles as inhibitors of p38 protein kinease, process for their preparation and pharmaceutical compositions containing them |
EP1226144B1 (en) * | 1999-10-21 | 2006-12-27 | F. Hoffmann-La Roche Ag | Alkylamino substituted bicyclic nitrogen heterocycles as inhibitors of p38 protein kinase |
WO2001038313A1 (en) | 1999-11-23 | 2001-05-31 | Smithkline Beecham Corporation | 3,4-DIHYDRO-(1H)QUINAZOLIN-2-ONE COMPOUNDS AS CSBP/p39 kINASE INHIBITORS |
US6759410B1 (en) | 1999-11-23 | 2004-07-06 | Smithline Beecham Corporation | 3,4-dihydro-(1H)-quinazolin-2-ones and their use as CSBP/p38 kinase inhibitors |
ATE296809T1 (de) * | 1999-11-23 | 2005-06-15 | Smithkline Beecham Corp | 3,4-dihydro-(1h)chinazolin-2-on-verbindungen als csbp/p38-kinase-inhibitoren |
US6525046B1 (en) | 2000-01-18 | 2003-02-25 | Boehringer Ingelheim Pharmaceuticals, Inc. | Aromatic heterocyclic compounds as antiinflammatory agents |
US6608052B2 (en) | 2000-02-16 | 2003-08-19 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compounds useful as anti-inflammatory agents |
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 |
WO2001070695A1 (en) * | 2000-03-22 | 2001-09-27 | Vertex Pharmaceuticals Incorporated | Pyridine derivatives as inhibitors of p38 |
JP4993838B2 (ja) * | 2000-08-11 | 2012-08-08 | バーテックス ファーマシューティカルズ インコーポレイテッド | P38のインヒビターとしてのピリジン誘導体 |
PE20020506A1 (es) * | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
US7998507B2 (en) * | 2000-09-21 | 2011-08-16 | Elan Pharma International Ltd. | Nanoparticulate compositions of mitogen-activated protein (MAP) kinase inhibitors |
DK1333833T3 (da) | 2000-10-23 | 2011-12-12 | Glaxosmithkline Llc | Ny trisubstitueret 8H-pyridol[2,3-d]pyrimidin-7-on-forbindelse til behandling af CSBP/RK/p38-kinnasemedierede sygdomme |
US6867300B2 (en) * | 2000-11-17 | 2005-03-15 | Bristol-Myers Squibb Company | Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors |
US6670357B2 (en) * | 2000-11-17 | 2003-12-30 | Bristol-Myers Squibb Company | Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors |
EP1345603A4 (en) * | 2000-12-20 | 2004-09-08 | Merck & Co Inc | P38 KINASE INHIBITORS (HALO-BENZO CARBONYL) HETEROCYCLO- FUSIONNES PHENYL |
JP4064818B2 (ja) * | 2001-02-12 | 2008-03-19 | エフ.ホフマン−ラ ロシュ アーゲー | 6−置換ピリド−ピリミジン類 |
GB0112348D0 (en) * | 2001-05-19 | 2001-07-11 | Smithkline Beecham Plc | Compounds |
GB2375771A (en) * | 2001-05-24 | 2002-11-27 | Univ Leeds | Decellularisation of tissue implant material |
EP1414455B1 (en) * | 2001-06-11 | 2008-11-26 | Vertex Pharmaceuticals Incorporated | Isoquinoline inhibitors of p38 |
US6819845B2 (en) | 2001-08-02 | 2004-11-16 | Ultradots, Inc. | Optical devices with engineered nonlinear nanocomposite materials |
US6710366B1 (en) | 2001-08-02 | 2004-03-23 | Ultradots, Inc. | Nanocomposite materials with engineered properties |
US6794265B2 (en) | 2001-08-02 | 2004-09-21 | Ultradots, Inc. | Methods of forming quantum dots of Group IV semiconductor materials |
US7005669B1 (en) | 2001-08-02 | 2006-02-28 | Ultradots, Inc. | Quantum dots, nanocomposite materials with quantum dots, devices with quantum dots, and related fabrication methods |
US20030066998A1 (en) | 2001-08-02 | 2003-04-10 | Lee Howard Wing Hoon | Quantum dots of Group IV semiconductor materials |
GB0124939D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124936D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124934D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124933D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124931D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124938D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124941D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124932D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
WO2003060102A2 (en) * | 2002-01-11 | 2003-07-24 | Vertex Pharmaceuticals Incorporated | Crystal structures of jnk-inhibitor complexes and binding pockets thereof |
EP1470112A1 (en) * | 2002-01-18 | 2004-10-27 | Pharmacia Corporation | Substituted pyridazinones as inhibitors of p38 |
DK1474395T3 (da) * | 2002-02-12 | 2008-02-11 | Smithkline Beecham Corp | Nicotinamidderivater, der er nyttige som p38-inhibitorer |
AU2003213806A1 (en) | 2002-02-25 | 2003-09-09 | Boehringer Ingelheim Pharmaceuticals, Inc. | 1,4-disubstituted benzofused cycloalkyl urea compounds useful in treating cytokine mediated diseases |
WO2003088958A2 (en) * | 2002-04-18 | 2003-10-30 | Pharmacia Corporation | Combinations of cox-2 inhibitors and other agents for the treatment of parkinson’s disease |
CA2482022A1 (en) | 2002-04-19 | 2003-10-30 | Smithkline Beecham Corporation | Novel compounds |
US7388009B2 (en) * | 2002-04-23 | 2008-06-17 | Bristol-Myers Squibb Company | Heteroaryl-substituted pyrrolo-triazine compounds useful as kinase inhibitors |
DE60325469D1 (de) * | 2002-04-23 | 2009-02-05 | Bristol Myers Squibb Co | Als kinase inhibitoren geeignete arylketonpyrrolotriazin-verbindungen |
EP1497019B1 (en) | 2002-04-23 | 2015-05-20 | Bristol-Myers Squibb Company | Pyrrolo-triazine aniline compounds useful as kinase inhibitors |
TW200400034A (en) * | 2002-05-20 | 2004-01-01 | Bristol Myers Squibb Co | Pyrazolo-pyrimidine aniline compounds useful as kinase inhibitors |
DE60317198T2 (de) * | 2002-05-23 | 2008-12-04 | Cytopia Research Pty. Ltd., Richmond | Proteinkinaseinhibitoren |
EP1707205A2 (en) | 2002-07-09 | 2006-10-04 | Boehringer Ingelheim Pharma GmbH & Co. KG | Pharmaceutical compositions of anticholinergics and p38 kinase inhibitors in the treatment of respiratory diseases |
GB0217757D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Novel compounds |
CN1980948B (zh) | 2002-11-27 | 2011-08-10 | Dmi生物科学公司 | 治疗由增强磷酸化介导的疾病和病况 |
GB0308201D0 (en) * | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
GB0308185D0 (en) * | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
GB0308186D0 (en) * | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
ES2386784T3 (es) * | 2003-05-01 | 2012-08-30 | Bristol-Myers Squibb Company | Compuestos de pirazol-amina útiles como inhibidores de quinasas |
CA2526285A1 (en) | 2003-05-15 | 2004-12-23 | Arqule, Inc. | Inhibitors of p38 and methods of using the same |
CA2528438A1 (en) * | 2003-06-03 | 2005-01-06 | Novartis Ag | P-38 inhibitors |
PT1641764E (pt) | 2003-06-26 | 2011-10-27 | Novartis Ag | Inibidores de p38 quinase a base de heterociclo de 5 elementos |
WO2005007632A1 (en) * | 2003-07-18 | 2005-01-27 | Pharmacia Corporation | Substituted pyridazinones as inhibitors of p38 |
ES2315703T3 (es) | 2003-07-25 | 2009-04-01 | Novartis Ag | Inhibidores de la quinasa p-38. |
GB0318814D0 (en) * | 2003-08-11 | 2003-09-10 | Smithkline Beecham Corp | Novel compounds |
US7419978B2 (en) * | 2003-10-22 | 2008-09-02 | Bristol-Myers Squibb Company | Phenyl-aniline substituted bicyclic compounds useful as kinase inhibitors |
ES2528302T3 (es) | 2003-12-03 | 2015-02-06 | Ym Biosciences Australia Pty Ltd | Heterociclos con 6 anillos de nitrógeno fenilsustituidos como inhibidores de la polimerización de microtúbulos |
GB0402143D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
WO2006010082A1 (en) | 2004-07-08 | 2006-01-26 | Arqule, Inc. | 1,4-disubstituted naphtalenes as inhibitors of p38 map kinase |
US7504521B2 (en) * | 2004-08-05 | 2009-03-17 | Bristol-Myers Squibb Co. | Methods for the preparation of pyrrolotriazine compounds |
US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
US7148348B2 (en) | 2004-08-12 | 2006-12-12 | Bristol-Myers Squibb Company | Process for preparing pyrrolotriazine aniline compounds useful as kinase inhibitors |
WO2006021848A1 (en) * | 2004-08-27 | 2006-03-02 | Ranbaxy Laboratories Limited | Anti-inflammatory agents |
US20080051416A1 (en) * | 2004-10-05 | 2008-02-28 | Smithkline Beecham Corporation | Novel Compounds |
JP2008517064A (ja) | 2004-10-19 | 2008-05-22 | アークル インコーポレイテッド | P38mapキナーゼのイミダゾオキサゾールおよびイミダゾチアゾール阻害剤の合成 |
PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
US20060178388A1 (en) * | 2005-02-04 | 2006-08-10 | Wrobleski Stephen T | Phenyl-substituted pyrimidine compounds useful as kinase inhibitors |
WO2006110298A2 (en) | 2005-03-25 | 2006-10-19 | Glaxo Group Limited | 8-alkyl/aryl-4-aryl-2-n- (alkylamino)-n'-substituted-n'-cyanoguanidino-8h-pyrido[2,3-d]pyrimidin-7-one compounds and use thereof |
CA2603163A1 (en) | 2005-03-25 | 2006-10-05 | Glaxo Group Limited | Process for preparing pyrido[2,3-d]pyrimidin-7-one and 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1h)-one derivatives |
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 |
MY145281A (en) | 2005-03-25 | 2012-01-13 | Glaxo Group Ltd | Novel compounds |
US20060235020A1 (en) * | 2005-04-18 | 2006-10-19 | Soojin Kim | Process for preparing salts of 4-[[5-[(cyclopropylamino)carbonyl]-2-methylphenyl]amino]-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide and novel stable forms produced therein |
GB0512429D0 (en) * | 2005-06-17 | 2005-07-27 | Smithkline Beecham Corp | Novel compound |
US7473784B2 (en) * | 2005-08-01 | 2009-01-06 | Bristol-Myers Squibb Company | Benzothiazole and azabenzothiazole compounds useful as kinase inhibitors |
EP1915373B1 (en) * | 2005-08-12 | 2013-05-22 | Merck Sharp & Dohme Corp. | Heterobicyclic compounds useful as p38 kinase inhibiting agents |
EP1953148B1 (en) | 2005-10-28 | 2012-02-29 | Takeda Pharmaceutical Company Limited | Heterocyclic amide compound and use thereof |
CN101395158A (zh) * | 2006-03-07 | 2009-03-25 | 百时美施贵宝公司 | 可作为激酶抑制剂的吡咯并三嗪苯胺前体药物化合物 |
CN101616667A (zh) | 2006-10-27 | 2009-12-30 | 百时美施贵宝公司 | 可用作激酶抑制剂的杂环酰胺化合物 |
US7943617B2 (en) | 2006-11-27 | 2011-05-17 | Bristol-Myers Squibb Company | Heterobicyclic compounds useful as kinase inhibitors |
WO2008114119A2 (en) * | 2007-03-20 | 2008-09-25 | Cadila Pharmaceuticals Limited | P38 inhibitors |
EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
EP2108641A1 (en) * | 2008-04-11 | 2009-10-14 | Laboratorios Almirall, S.A. | New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors |
EP2111861A1 (en) | 2008-04-21 | 2009-10-28 | Ranbaxy Laboratories Limited | Compositions of phosphodiesterase type IV inhibitors |
CN102131805A (zh) | 2008-06-20 | 2011-07-20 | 百时美施贵宝公司 | 用作激酶抑制剂的咪唑并吡啶和咪唑并吡嗪化合物 |
EP2307411B1 (en) * | 2008-06-20 | 2014-01-01 | Bristol-Myers Squibb Company | Triazolopyridine compounds useful as kinase inhibitors |
WO2010038428A1 (ja) * | 2008-09-30 | 2010-04-08 | 武田薬品工業株式会社 | タキサン系抗がん剤の置き換え薬 |
SG10201407409WA (en) | 2009-02-06 | 2015-01-29 | Elan Pharm Inc | Inhibitors of jun n-terminal kinase |
GB0902648D0 (en) | 2009-02-17 | 2009-04-01 | Argenta Discovery Ltd | Pharmaceutical compounds and compositions |
GB0908317D0 (en) * | 2009-05-14 | 2009-06-24 | Argenta Discovery Ltd | Pharmaceutical compounds and compositions |
WO2012031057A1 (en) | 2010-09-01 | 2012-03-08 | Bristol-Myers Squibb Company | Bms- 582949 for the treatment of resistant rheumatic disease |
EP3081568B1 (en) * | 2011-05-09 | 2019-11-13 | Eip Pharma, LLC | Compositions and methods for treating alzheimer's disease |
US20150044178A1 (en) | 2011-12-28 | 2015-02-12 | Kyoto Prefectural Public University Corporation | Normalization of culture of corneal endothelial cells |
CN103772392A (zh) * | 2012-10-23 | 2014-05-07 | 杨子娇 | 一类治疗房角狭窄的化合物及其用途 |
US10813920B2 (en) | 2013-11-14 | 2020-10-27 | The Doshisha | Drug for treating corneal endothelium by promoting cell proliferation or inhibiting cell damage |
WO2016007616A1 (en) | 2014-07-09 | 2016-01-14 | Eip Pharma, Llc | Methods for treating neurologic disorders |
DK3368052T3 (da) | 2015-10-27 | 2022-03-14 | Childrens Hospital Med Ct | Anvendelse af mapk-hæmmere for at nedbringe tabet af hæmatopoietiske stamceller under ex vivo-dyrkning og -genmanipulation |
US20190060286A1 (en) | 2016-02-29 | 2019-02-28 | University Of Florida Research Foundation, Incorpo | Chemotherapeutic Methods |
WO2019056003A1 (en) | 2017-09-18 | 2019-03-21 | Eip Pharma, Llc | CO-CRYSTALS FROM NEFLAMAPIMOD (VX -745) |
WO2019071147A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | INHIBITORS OF KINASE P38 REDUCING EXPRESSION OF DUX4 GENE AND DOWNSTREAM GENES FOR THE TREATMENT OF FSHD |
US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
HRP20220331T1 (hr) | 2018-03-08 | 2022-05-13 | Incyte Corporation | Spojevi aminopirazin diola kao inhibitori pi3k-y |
US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
EP3889156A4 (en) * | 2018-11-30 | 2022-07-20 | Shanghai Pharmaceuticals Holding Co., Ltd. | HETEROCYCLIC COMPOUND CONTAINING NITROGEN, COMPOSITION BASED THEREOF, METHOD FOR THE PREPARATION AND USE THEREOF |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5716972A (en) * | 1993-01-13 | 1998-02-10 | Smithkline Beecham Corporation | Pyridyl substituted imidazoles |
IL110296A (en) * | 1993-07-16 | 1999-12-31 | Smithkline Beecham Corp | Imidazole compounds process for their preparation and pharmaceutical compositions containing them |
WO1995021654A1 (en) * | 1994-02-10 | 1995-08-17 | Vladimir Ivanovich Ivanov | Device for phono-electrophoresis |
US5559137A (en) * | 1994-05-16 | 1996-09-24 | Smithkline Beecham Corp. | Compounds |
WO1996021654A1 (en) * | 1995-01-12 | 1996-07-18 | Smithkline Beecham Corporation | Novel compounds |
US5717100A (en) * | 1995-10-06 | 1998-02-10 | Merck & Co., Inc. | Substituted imidazoles having anti-cancer and cytokine inhibitory activity |
NZ321738A (en) * | 1995-10-06 | 1999-11-29 | Merck & Co Inc | 3-pyridine-2-heterocyclic substituted imidazoles and medicaments having anti-cancer and cytokine inhibitory activity |
GB9523675D0 (en) * | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
ZA97175B (en) * | 1996-01-11 | 1997-11-04 | Smithkline Beecham Corp | Novel substituted imidazole compounds. |
WO1997044467A1 (en) * | 1996-05-20 | 1997-11-27 | Signal Pharmaceuticals, Inc. | MITOGEN-ACTIVATED PROTEIN KINASE p38-2 AND METHODS OF USE THEREFOR |
JP3418624B2 (ja) * | 1996-06-10 | 2003-06-23 | メルク エンド カンパニー インコーポレーテッド | サイトカイン阻害活性を有する置換イミダゾール類 |
GB9613021D0 (en) * | 1996-06-21 | 1996-08-28 | Pharmacia Spa | Bicyclic 4-aralkylaminopyrimidine derivatives as tyrosine kinase inhibitors |
US6417202B1 (en) * | 1996-07-11 | 2002-07-09 | Pfizer Inc. | Pyridylpyrrole compounds useful as interleukin-and TNF antagonists |
WO1998006715A1 (en) * | 1996-08-09 | 1998-02-19 | Smithkline Beecham Corporation | Novel piperazine containing compounds |
US5945418A (en) * | 1996-12-18 | 1999-08-31 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
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