CA2288741A1 - 4-aryl-3(5)-heteroaryl substituted pyrazoles as p38 kinase inhibitors - Google Patents
4-aryl-3(5)-heteroaryl substituted pyrazoles as p38 kinase inhibitors Download PDFInfo
- Publication number
- CA2288741A1 CA2288741A1 CA002288741A CA2288741A CA2288741A1 CA 2288741 A1 CA2288741 A1 CA 2288741A1 CA 002288741 A CA002288741 A CA 002288741A CA 2288741 A CA2288741 A CA 2288741A CA 2288741 A1 CA2288741 A1 CA 2288741A1
- Authority
- CA
- Canada
- Prior art keywords
- pyridinyl
- pyrazol
- fluorophenyl
- methyl
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 title claims abstract description 36
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 title claims abstract description 36
- 150000003217 pyrazoles Chemical class 0.000 title abstract description 19
- 229940043355 kinase inhibitor Drugs 0.000 title description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
- -1 amino, aminocarbonyl Chemical group 0.000 claims abstract description 337
- 150000001875 compounds Chemical class 0.000 claims abstract description 104
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 51
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 36
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 33
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 32
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 31
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 29
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 25
- 125000001769 aryl amino group Chemical group 0.000 claims abstract description 24
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 23
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 22
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 21
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 21
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 17
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 15
- 125000003118 aryl group Chemical group 0.000 claims abstract description 15
- 230000001404 mediated effect Effects 0.000 claims abstract description 15
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 15
- 125000006319 alkynyl amino group Chemical group 0.000 claims abstract description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 11
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims abstract description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 9
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 8
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims abstract description 7
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims abstract description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract description 4
- 150000003254 radicals Chemical group 0.000 claims description 106
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 41
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 32
- 208000035475 disorder Diseases 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 27
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 125000001145 hydrido group Chemical group *[H] 0.000 claims description 20
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 12
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 11
- 206010061218 Inflammation Diseases 0.000 claims description 10
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 10
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- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 9
- OHAXWEJEKCXBIP-UHFFFAOYSA-N 4-(4-fluorophenyl)-5-pyridin-4-yl-1h-pyrazol-3-amine Chemical compound NC1=NNC(C=2C=CN=CC=2)=C1C1=CC=C(F)C=C1 OHAXWEJEKCXBIP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
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- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 9
- 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims description 8
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 8
- FNEJUCNPMRBTLD-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-1-methylpyrazol-3-yl]pyridine Chemical compound N=1N(C)C=C(C=2C=CC(F)=CC=2)C=1C1=CC=NC=C1 FNEJUCNPMRBTLD-UHFFFAOYSA-N 0.000 claims description 7
- UCYCFYFNBWRJIL-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-1h-pyrazol-5-yl]pyridine Chemical compound C1=CC(F)=CC=C1C1=CNN=C1C1=CC=NC=C1 UCYCFYFNBWRJIL-UHFFFAOYSA-N 0.000 claims description 7
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 7
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 claims description 7
- 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 7
- ZVCFVJLZJGIPAY-UHFFFAOYSA-N n-[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-pyrazol-3-yl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=NNC(C=2C=CN=CC=2)=C1C1=CC=C(F)C=C1 ZVCFVJLZJGIPAY-UHFFFAOYSA-N 0.000 claims description 7
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 7
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 6
- 239000004305 biphenyl Substances 0.000 claims description 6
- 235000010290 biphenyl Nutrition 0.000 claims description 6
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
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- ZTVUVHMVLWWIAS-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-pyrazol-3-yl]-3-methylurea Chemical compound CNC(=O)NC1=NNC(C=2C=CN=CC=2)=C1C1=CC=C(F)C=C1 ZTVUVHMVLWWIAS-UHFFFAOYSA-N 0.000 claims description 5
- JSFYQSJJVQMXLF-UHFFFAOYSA-N 2-[4-(4-fluorophenyl)-3-pyridin-4-ylpyrazol-1-yl]-n,n-dimethylethanamine Chemical compound N=1N(CCN(C)C)C=C(C=2C=CC(F)=CC=2)C=1C1=CC=NC=C1 JSFYQSJJVQMXLF-UHFFFAOYSA-N 0.000 claims description 5
- LZTNKQMWDZLVCY-UHFFFAOYSA-N 2-[4-(4-fluorophenyl)-3-pyridin-4-ylpyrazol-1-yl]ethanol Chemical compound N=1N(CCO)C=C(C=2C=CC(F)=CC=2)C=1C1=CC=NC=C1 LZTNKQMWDZLVCY-UHFFFAOYSA-N 0.000 claims description 5
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
- FXTBNPRXFDHPMN-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-methyl-5-pyridin-4-ylpyrazol-3-amine Chemical compound NC=1N(C)N=C(C=2C=CN=CC=2)C=1C1=CC=C(Cl)C=C1 FXTBNPRXFDHPMN-UHFFFAOYSA-N 0.000 claims description 5
- DKUGHDSTBVGJJW-UHFFFAOYSA-N 4-(5-methyl-4-phenyl-1h-pyrazol-3-yl)pyridine Chemical compound CC1=NNC(C=2C=CN=CC=2)=C1C1=CC=CC=C1 DKUGHDSTBVGJJW-UHFFFAOYSA-N 0.000 claims description 5
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- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000006003 dichloroethyl group Chemical group 0.000 claims description 5
- 125000006001 difluoroethyl group Chemical group 0.000 claims description 5
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- 125000006343 heptafluoro propyl group Chemical group 0.000 claims description 5
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- 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 5
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- JCJQRHJXLMGLSV-UHFFFAOYSA-N 4-[2-[4-(4-fluorophenyl)-3-pyridin-4-ylpyrazol-1-yl]ethyl]morpholine Chemical compound C1=CC(F)=CC=C1C(C(=N1)C=2C=CN=CC=2)=CN1CCN1CCOCC1 JCJQRHJXLMGLSV-UHFFFAOYSA-N 0.000 claims description 4
- RLBDPHUIKKSEPY-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-pyridin-4-yl-1h-pyrazol-3-yl]urea Chemical compound NC(=O)NC1=NNC(C=2C=CN=CC=2)=C1C1=CC=C(F)C=C1 RLBDPHUIKKSEPY-UHFFFAOYSA-N 0.000 claims description 4
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- WUFIEVBIPYUAGD-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-3-(sulfamoylamino)-1h-pyrazol-5-yl]pyridine Chemical compound NS(=O)(=O)NC1=NNC(C=2C=CN=CC=2)=C1C1=CC=C(F)C=C1 WUFIEVBIPYUAGD-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
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- Dermatology (AREA)
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- Diabetes (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4753597P | 1997-05-22 | 1997-05-22 | |
| US60/047,535 | 1997-05-22 | ||
| PCT/US1998/010807 WO1998052937A2 (en) | 1997-05-22 | 1998-05-22 | 4-aryl-3(5)-heteroaryl substituted pyrazoles as p38 kinase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2288741A1 true CA2288741A1 (en) | 1998-11-26 |
Family
ID=21949533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002288741A Abandoned CA2288741A1 (en) | 1997-05-22 | 1998-05-22 | 4-aryl-3(5)-heteroaryl substituted pyrazoles as p38 kinase inhibitors |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US5932576A (https=) |
| EP (1) | EP0983260A2 (https=) |
| JP (1) | JP2002502379A (https=) |
| KR (1) | KR20010012808A (https=) |
| CN (1) | CN1264376A (https=) |
| AR (1) | AR037061A1 (https=) |
| AU (1) | AU755498B2 (https=) |
| BR (1) | BR9809451A (https=) |
| CA (1) | CA2288741A1 (https=) |
| IL (1) | IL132736A0 (https=) |
| NO (1) | NO995635L (https=) |
| PL (1) | PL336990A1 (https=) |
| RU (1) | RU2249591C2 (https=) |
| WO (1) | WO1998052937A2 (https=) |
Families Citing this family (125)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US5559137A (en) * | 1994-05-16 | 1996-09-24 | Smithkline Beecham Corp. | Compounds |
| US6087496A (en) * | 1998-05-22 | 2000-07-11 | G. D. Searle & Co. | Substituted pyrazoles suitable as p38 kinase inhibitors |
| US6514977B1 (en) * | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
| EP1019394A1 (en) | 1997-05-22 | 2000-07-19 | G.D. Searle & Co. | PYRAZOLE DERIVATIVES AS p38 KINASE INHIBITORS |
| US6979686B1 (en) | 2001-12-07 | 2005-12-27 | Pharmacia Corporation | Substituted pyrazoles as p38 kinase inhibitors |
| AU7966198A (en) | 1997-06-13 | 1998-12-30 | Smithkline Beecham Corporation | Novel pyrazole and pyrazoline substituted compounds |
| US6339099B1 (en) * | 1997-06-20 | 2002-01-15 | Dupont Pharmaceuticals Company | Guanidine mimics as factor Xa inhibitors |
| US7301021B2 (en) | 1997-07-02 | 2007-11-27 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| ATE529109T1 (de) * | 1997-12-22 | 2011-11-15 | Bayer Healthcare Llc | Hemmung der p38 kinase aktivität durch substituierte heterocyclische harnstoffe |
| MY132496A (en) * | 1998-05-11 | 2007-10-31 | Vertex Pharma | Inhibitors of p38 |
| US6858617B2 (en) | 1998-05-26 | 2005-02-22 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| US7605149B1 (en) | 1998-07-13 | 2009-10-20 | University Of South Florida | Modulation of the phospholipase A2 pathway as a therapeutic |
| US6649617B1 (en) | 1998-10-07 | 2003-11-18 | Smithkline Beecham Corporation | Treatment for stroke management |
| DE69914357T2 (de) | 1998-11-04 | 2004-11-11 | Smithkline Beecham Corp. | Pyridin-4-yl oder pyrimidin-4-yl substituierte pyrazine |
| SA99191255B1 (ar) | 1998-11-30 | 2006-11-25 | جي دي سيرل اند كو | مركبات سيليكوكسيب celecoxib |
| CA2355075C (en) | 1998-12-16 | 2009-12-08 | Aventis Pharma Limited | Heteroaryl-cyclic acetals |
| KR100711538B1 (ko) * | 1998-12-25 | 2007-04-27 | 아스카 세이야쿠 가부시키가이샤 | 아미노피라졸 유도체 |
| EP1158985B1 (en) | 1999-01-13 | 2011-12-28 | Bayer HealthCare LLC | OMEGA-CARBOXY ARYL SUBSTITUTED DIPHENYL UREAS AS p38 KINASE INHIBITORS |
| US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| 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 |
| US7122666B2 (en) * | 1999-07-21 | 2006-10-17 | Sankyo Company, Limited | Heteroaryl-substituted pyrrole derivatives, their preparation and their therapeutic uses |
| US6808902B1 (en) | 1999-11-12 | 2004-10-26 | Amgen Inc. | Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules |
| ATE281439T1 (de) | 1999-11-23 | 2004-11-15 | Smithkline Beecham Corp | 3,4-dihydro-(1h)chinazolin-2-on-verbindungen als csbp/p38-kinase-inhibitoren |
| JP2003514900A (ja) | 1999-11-23 | 2003-04-22 | スミスクライン・ビーチャム・コーポレイション | ＣＳＢＰ／ｐ３８キナーゼ阻害剤としての３，４−ジヒドロ−（１Ｈ）−キナゾリン−２−オン化合物 |
| EP1233950B1 (en) | 1999-11-23 | 2005-10-05 | Smithkline Beecham Corporation | 3,4-DIHYDRO-(1H)QUINAZOLIN-2-ONE COMPOUNDS AS CSBP/P39 kINASE INHIBITORS |
| CA2369502A1 (en) * | 2000-02-05 | 2001-08-09 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of erk |
| KR20010111298A (ko) | 2000-02-05 | 2001-12-17 | 버텍스 파마슈티칼스 인코포레이티드 | Ｅｒｋ의 억제제로서 유용한 피라졸 조성물 |
| 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 |
| GB0016787D0 (en) | 2000-07-07 | 2000-08-30 | Pfizer Ltd | Compounds useful in therapy |
| PE20020506A1 (es) * | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| 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 |
| ATE291020T1 (de) * | 2001-02-02 | 2005-04-15 | Smithkline Beecham Corp | Pyrazolderivate gegen tgf überexprimierung |
| AU2002338642A1 (en) * | 2001-04-13 | 2002-10-28 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
| US7074801B1 (en) | 2001-04-26 | 2006-07-11 | Eisai Co., Ltd. | Nitrogen-containing condensed cyclic compound having a pyrazolyl group as a substituent group and pharmaceutical composition thereof |
| GB0112348D0 (en) * | 2001-05-19 | 2001-07-11 | Smithkline Beecham Plc | Compounds |
| EP2295081B1 (en) | 2001-06-26 | 2018-10-31 | Amgen Inc. | Antibodies to OPGL |
| EP1423380B1 (en) * | 2001-08-03 | 2010-12-15 | Vertex Pharmaceuticals Incorporated | Pyrazole-derived kinase inhibitors and uses thereof |
| US20040248950A1 (en) * | 2001-08-24 | 2004-12-09 | Natsuki Ishizuka | Apo ai expression accelerating agent |
| AU2002330096B2 (en) | 2001-09-25 | 2007-11-08 | Pharmacia Corporation | Process for making substituted pyrazoles |
| US7057049B2 (en) | 2001-09-25 | 2006-06-06 | Pharmacia Corporation | Process for making substituted pyrazoles |
| 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 |
| GB0124932D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124939D0 (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 |
| GB0124933D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| JP4518378B2 (ja) * | 2001-10-29 | 2010-08-04 | ベーリンガー インゲルハイム インテルナツィオナール ゲゼルシャフト ミット ベシュレンクテル ハフツング | エネルギー恒常性および細胞小器官代謝の調節に関与するＭｎｋキナーゼ相同性タンパク質 |
| ATE374753T1 (de) * | 2001-12-21 | 2007-10-15 | Vernalis Cambridge Ltd | 3-(2,4)dihydroxyphenyl-4-phenylpyrazole und deren medizinische verwendung |
| SI1478358T1 (sl) | 2002-02-11 | 2013-09-30 | Bayer Healthcare Llc | Sorafenib tozilat za zdravljenje bolezni, značilnih po abnormalni angiogenezi |
| ATE375980T1 (de) | 2002-02-12 | 2007-11-15 | Smithkline Beecham Corp | Nicotinamide und deren verwendung als p38 inhibitoren |
| AR039241A1 (es) * | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
| US20050124620A1 (en) * | 2002-04-09 | 2005-06-09 | Martyn Frederickson | Pharmaceutical compounds |
| PT1497019E (pt) | 2002-04-23 | 2015-09-10 | Bristol Myers Squibb Co | Compostos de pirrolotriazina anilina úteis como inibidores de quinase |
| JP2005529919A (ja) * | 2002-05-10 | 2005-10-06 | スミスクライン ビーチャム コーポレーション | 治療用化合物 |
| ES2278170T3 (es) | 2002-07-09 | 2007-08-01 | BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG | Composiciones farmaceuticas de anticolinergicos e inhibidores de la quinasa p38 en el tratamiento de enfermedades respiratorias. |
| GB0217757D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Novel compounds |
| UA80295C2 (en) * | 2002-09-06 | 2007-09-10 | Biogen Inc | Pyrazolopyridines and using the same |
| PL379544A1 (pl) * | 2002-09-09 | 2006-10-02 | Amgen Inc. | 1,4,5-podstawione pochodne 1,2-dihydro-pirazol-3-onu i 3-alkoksy 1H-pirazolu jako środki obniżające poziom TNF-alfa oraz interleukin do leczenia stanów zapalnych |
| CA2496295C (en) | 2002-09-18 | 2010-11-23 | Michael John Munchhof | Novels pyrazole compounds as transforming growth factor (tgf) inhibitors |
| CA2497971A1 (en) | 2002-09-18 | 2004-04-01 | Pfizer Products Inc. | Triazole derivatives as transforming growth factor (tgf) inhibitors |
| EP1542995A1 (en) | 2002-09-18 | 2005-06-22 | Pfizer Products Inc. | Novel isothiazole and isoxazole compounds as transforming growth factor (tgf) inhibitors |
| AU2003256003A1 (en) | 2002-09-18 | 2004-04-08 | Pfizer Products Inc. | Novel oxazole and thiazole compounds as transforming growth factor (TGF) inhibitors |
| MXPA05002981A (es) | 2002-09-18 | 2005-06-22 | Pfizer Prod Inc | Nuevos compuestos de imidazol como inhibidores del factor de crecimiento transformante (tgf). |
| CN100519552C (zh) | 2002-09-25 | 2009-07-29 | 宇部兴产株式会社 | 吡唑化合物 |
| US7622471B2 (en) | 2003-02-07 | 2009-11-24 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives having a pyridazine and pyridine functionality |
| CL2004000234A1 (es) * | 2003-02-12 | 2005-04-15 | Biogen Idec Inc | Compuestos derivados 3-(piridin-2-il)-4-heteroaril-pirazol sustituidos, antagonistas de aik5 y/o aik4; composicion farmaceutica y uso del compuesto en el tratamiento de desordenes fibroticos como esclerodermia, lupus nefritico, cicatrizacion de herid |
| CL2004000366A1 (es) * | 2003-02-26 | 2005-01-07 | Pharmacia Corp Sa Organizada B | USO DE UNA COMBINACION DE UN COMPUESTO DERIVADO DE PIRAZOL INHIBIDOR DE QUINASA p38, Y UN INHIBIDOR DE ACE PARA TRATAR DISFUNCION RENAL, ENFERMEDAD CARDIOVASCULAR Y VASCULAR, RETINOPATIA, NEUROPATIA, EDEMA, DISFUNCION ENDOTELIAL O INSULINOPATIA. |
| PA8595001A1 (es) | 2003-03-04 | 2004-09-28 | Pfizer Prod Inc | Nuevos compuestos heteroaromaticos condensados que son inhibidores del factor de crecimiento transforante (tgf) |
| EP1606019A1 (en) * | 2003-03-07 | 2005-12-21 | The University Court of The University of Aberdeen | Cannabinoid receptor inverse agonists and neutral antagonists as therapeutic agents for the treatment of bone disorders |
| GB0308201D0 (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 |
| GB0308185D0 (en) * | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| ES2275218T3 (es) | 2003-05-07 | 2007-06-01 | Osteologix A/S | Sales de estroncio hidrosolubles para el tratamiento de afecciones de cartilagos y/o huesos. |
| EP1636585B2 (en) | 2003-05-20 | 2012-06-13 | Bayer HealthCare LLC | Diaryl ureas with kinase inhibiting activity |
| US7652044B2 (en) * | 2003-06-03 | 2010-01-26 | Novartis A.G. | P-38 inhibitors |
| PL2298743T3 (pl) | 2003-06-26 | 2013-02-28 | Novartis Ag | Inhibitory kinaz P38 na bazie 5-członowych heterocykli |
| EP1663978B1 (en) | 2003-07-23 | 2007-11-28 | Bayer Pharmaceuticals Corporation | Fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions |
| EP1687284B1 (en) * | 2003-07-25 | 2008-10-29 | Novartis AG | p-38 KINASE INHIBITORS |
| 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 |
| GB0402143D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| 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 |
| TW200618803A (en) | 2004-08-12 | 2006-06-16 | Bristol Myers Squibb Co | Process for preparing pyrrolotriazine aniline compounds useful as kinase inhibitors |
| EA012119B1 (ru) | 2004-08-12 | 2009-08-28 | Пфайзер Инк. | ПРОИЗВОДНЫЕ ТРИАЗОЛОПИРИДИНСУЛЬФАНИЛА В КАЧЕСТВЕ ИНГИБИТОРОВ p38 MAP КИНАЗЫ |
| US20080051416A1 (en) * | 2004-10-05 | 2008-02-28 | Smithkline Beecham Corporation | Novel Compounds |
| 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 |
| TW200639163A (en) | 2005-02-04 | 2006-11-16 | Genentech Inc | RAF inhibitor compounds and methods |
| 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 |
| US20060252807A1 (en) * | 2005-04-22 | 2006-11-09 | Kalypsys, Inc. | Novel ortho-terphenyl inhibitors of p38 kinase and methods of treating inflammatory disorders |
| 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 |
| US20070054884A1 (en) * | 2005-08-31 | 2007-03-08 | Emergent Product Development Gaithersburg Inc. | 4-substituted 2-aryloxyphenol derivatives as antibacterial agents |
| JP2009513615A (ja) * | 2005-10-28 | 2009-04-02 | アストラゼネカ アクチボラグ | 癌の治療においてチロシンキナーゼ阻害剤として使用するための４−（３−アミノピラゾール）ピリミジン誘導体 |
| BRPI0620415A2 (pt) * | 2005-12-23 | 2011-11-08 | Astrazeneca Ab | composto e sais farmaceuticamente e farmacologicamente aceitáveis do mesmo, e enantiÈmeros do composto e sais do mesmo, composição farmaceutica, e, uso de um composto opcionalmente em combinação com um agonista do receptor de gabab, e, métodos para o tratamento de doença, de um distúrbio, e de sìndrome |
| KR20080107408A (ko) * | 2006-03-07 | 2008-12-10 | 브리스톨-마이어스 스큅 컴퍼니 | 키나제 억제제로서 유용한 피롤로트리아진 아닐린 전구약물화합물 |
| JP2007205153A (ja) * | 2006-08-07 | 2007-08-16 | Seiki Hanbai Co Ltd | 網戸用ネットの押さえ部材 |
| US8128460B2 (en) * | 2006-09-14 | 2012-03-06 | The Material Works, Ltd. | Method of producing rust inhibitive sheet metal through scale removal with a slurry blasting descaling cell |
| EP2083816A2 (en) * | 2006-10-27 | 2009-08-05 | Brystol-Myers Squibb Company | Heterocyclic amide compounds useful as kinase inhibitors |
| US7943617B2 (en) * | 2006-11-27 | 2011-05-17 | Bristol-Myers Squibb Company | Heterobicyclic compounds useful as kinase inhibitors |
| US8153792B2 (en) * | 2007-02-13 | 2012-04-10 | Ab Science | Process for the synthesis of 2-aminothiazole compounds as kinase inhibitors |
| GB0702862D0 (en) * | 2007-02-14 | 2007-03-28 | Univ Aberdeen | Therapeutic compounds |
| KR20100014565A (ko) * | 2007-04-11 | 2010-02-10 | 알콘 리서치, 리미티드 | 알레르기성 비염 및 알레르기성 결막염을 치료하기 위한 ｔｎｆａ의 억제제 및 항히스타민의 용도 |
| US20090182035A1 (en) * | 2007-04-11 | 2009-07-16 | Alcon Research, Ltd. | Use of a combination of olopatadine and cilomilast to treat non-infectious rhinitis and allergic conjunctivitis |
| EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
| WO2009028631A1 (ja) * | 2007-08-29 | 2009-03-05 | Senju Pharmaceutical Co., Ltd. | 角膜内皮細胞接着促進剤 |
| AU2009235634B8 (en) * | 2008-04-08 | 2013-05-23 | Grunenthal Gmbh | Substituted sulfonamide derivatives |
| WO2009155389A1 (en) * | 2008-06-20 | 2009-12-23 | Bristol-Myers Squibb Company | Triazolopyridine compounds useful as kinase 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 |
| CN102177138A (zh) * | 2008-10-23 | 2011-09-07 | 隆萨有限公司 | 合成取代的吡唑类的方法 |
| CN102548536A (zh) * | 2009-10-01 | 2012-07-04 | 爱尔康研究有限公司 | 奥洛他定组合物及其用途 |
| EP2308866A1 (de) | 2009-10-09 | 2011-04-13 | Bayer CropScience AG | Phenylpyri(mi)dinylpyrazole und ihre Verwendung als Fungizide |
| CN102762551A (zh) | 2009-12-21 | 2012-10-31 | 拜尔农作物科学股份公司 | 噻吩基吡(嘧)啶基吡唑及其用于防治植物致病菌的用途 |
| AR081810A1 (es) | 2010-04-07 | 2012-10-24 | Bayer Cropscience Ag | Piridinilpirazoles biciclicos |
| WO2012031057A1 (en) | 2010-09-01 | 2012-03-08 | Bristol-Myers Squibb Company | Bms- 582949 for the treatment of resistant rheumatic disease |
| AR086992A1 (es) | 2011-06-20 | 2014-02-05 | Bayer Ip Gmbh | Tienilpiri(mi)dinilpirazoles |
| JP6211522B2 (ja) | 2011-10-06 | 2017-10-11 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ | ヘテロシクリルピリ（ミ）ジニルピラゾール |
| MX355016B (es) | 2011-10-06 | 2018-04-02 | Bayer Ip Gmbh | Heterociclilpiri(mi)dinilpirazoles como fungicidas. |
| CN103360315B (zh) * | 2013-07-22 | 2015-03-04 | 山东大学 | 一种芳杂氧乙酰肼类衍生物及其制备方法与应用 |
| CA3121202A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| WO2023164538A1 (en) * | 2022-02-23 | 2023-08-31 | Biohaven Therapeutics Ltd. | Pyrazolyl compounds as kv7 channel activators |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1261124B (de) * | 1961-09-22 | 1968-02-15 | Hoechst Ag | Verfahren zur Herstellung von Pyrazolen |
| GB1245283A (en) * | 1968-10-04 | 1971-09-08 | Labaz | Pyrazole derivatives |
| US3984431A (en) * | 1972-03-15 | 1976-10-05 | Claude Gueremy | Derivatives of pyrazole-5-acetic acid |
| FR2509729A1 (fr) * | 1981-07-15 | 1983-01-21 | Pharmindustrie | Nouveau procede de preparation de derives du diphenyl-3,4 methyl-5 pyrazole |
| US5051518A (en) * | 1987-05-29 | 1991-09-24 | Ortho Pharmaceutical Corporation | Pharmacologically active 2- and 3-substituted (1',5'-diaryl-3-pyrazolyl)-N-hydroxypropanamides |
| PH27357A (en) * | 1989-09-22 | 1993-06-21 | Fujisawa Pharmaceutical Co | Pyrazole derivatives and pharmaceutical compositions comprising the same |
| JP2753659B2 (ja) * | 1990-09-03 | 1998-05-20 | 株式会社大塚製薬工場 | ピラゾール誘導体 |
| JPH04145081A (ja) * | 1990-10-06 | 1992-05-19 | Kumiai Chem Ind Co Ltd | ピラゾールカルボン酸誘導体及び除草剤 |
| WO1992019615A2 (en) * | 1991-04-24 | 1992-11-12 | E.I. Du Pont De Nemours And Company | Fungicidal pyrazoles, pyrazolines and tetrahydropyridazines |
| US5356897A (en) * | 1991-09-09 | 1994-10-18 | Fujisawa Pharmaceutical Co., Ltd. | 3-(heteroaryl)-pyrazololi[1,5-a]pyrimidines |
| GB9204958D0 (en) * | 1992-03-06 | 1992-04-22 | Fujisawa Pharmaceutical Co | Thiazole derivatives |
| US5593992A (en) * | 1993-07-16 | 1997-01-14 | Smithkline Beecham Corporation | Compounds |
| DE4328228A1 (de) * | 1993-08-23 | 1995-03-02 | Basf Ag | Verfahren zur Herstellung von Pyrazol und dessen Derivaten |
| US5559137A (en) * | 1994-05-16 | 1996-09-24 | Smithkline Beecham Corp. | Compounds |
| US5486534A (en) * | 1994-07-21 | 1996-01-23 | G. D. Searle & Co. | 3,4-substituted pyrazoles for the treatment of inflammation |
| JPH0899975A (ja) * | 1994-08-05 | 1996-04-16 | Nippon Bayeragrochem Kk | ５員複素環置換テトラゾリノン誘導体および除草剤 |
| JP3734180B2 (ja) * | 1994-12-28 | 2006-01-11 | エーザイ株式会社 | 新規ピラゾール誘導体 |
| JPH11508267A (ja) * | 1995-06-26 | 1999-07-21 | 藤沢薬品工業株式会社 | ピラゾール化合物および医薬組成物 |
| GB2361824B (en) * | 2000-04-27 | 2004-05-26 | Roke Manor Research | Improvements in or relating to electronic timing systems |
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1998
- 1998-05-22 IL IL13273698A patent/IL132736A0/xx unknown
- 1998-05-22 KR KR1019997010771A patent/KR20010012808A/ko not_active Ceased
- 1998-05-22 CA CA002288741A patent/CA2288741A1/en not_active Abandoned
- 1998-05-22 AU AU76981/98A patent/AU755498B2/en not_active Ceased
- 1998-05-22 JP JP55075598A patent/JP2002502379A/ja not_active Abandoned
- 1998-05-22 BR BR9809451-3A patent/BR9809451A/pt not_active Application Discontinuation
- 1998-05-22 US US09/083,923 patent/US5932576A/en not_active Expired - Fee Related
- 1998-05-22 CN CN98807326A patent/CN1264376A/zh active Pending
- 1998-05-22 EP EP98924924A patent/EP0983260A2/en not_active Withdrawn
- 1998-05-22 PL PL98336990A patent/PL336990A1/xx unknown
- 1998-05-22 WO PCT/US1998/010807 patent/WO1998052937A2/en not_active Ceased
- 1998-05-22 RU RU99126510/04A patent/RU2249591C2/ru not_active IP Right Cessation
- 1998-05-22 AR ARP980102380A patent/AR037061A1/es unknown
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1999
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| RU2249591C2 (ru) | 2005-04-10 |
| IL132736A0 (en) | 2001-03-19 |
| AU7698198A (en) | 1998-12-11 |
| EP0983260A2 (en) | 2000-03-08 |
| AR037061A1 (es) | 2004-10-20 |
| NO995635D0 (no) | 1999-11-17 |
| CN1264376A (zh) | 2000-08-23 |
| AU755498B2 (en) | 2002-12-12 |
| WO1998052937A3 (en) | 1999-03-11 |
| JP2002502379A (ja) | 2002-01-22 |
| US5932576A (en) | 1999-08-03 |
| PL336990A1 (en) | 2000-07-31 |
| BR9809451A (pt) | 2000-06-20 |
| KR20010012808A (ko) | 2001-02-26 |
| WO1998052937A2 (en) | 1998-11-26 |
| NO995635L (no) | 1999-11-17 |
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Effective date: 20080522 |