ES2259331T3 - Derivados de pirazol fusionado como inhibidores de la proteina quinasa. - Google Patents
Derivados de pirazol fusionado como inhibidores de la proteina quinasa.Info
- Publication number
- ES2259331T3 ES2259331T3 ES01960928T ES01960928T ES2259331T3 ES 2259331 T3 ES2259331 T3 ES 2259331T3 ES 01960928 T ES01960928 T ES 01960928T ES 01960928 T ES01960928 T ES 01960928T ES 2259331 T3 ES2259331 T3 ES 2259331T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- formula
- fluorophenyl
- pyrazolo
- compound
- 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.)
- Expired - Lifetime
Links
- 239000003112 inhibitor Substances 0.000 title description 9
- 108090000623 proteins and genes Proteins 0.000 title description 3
- 102000004169 proteins and genes Human genes 0.000 title description 2
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 30
- 201000010099 disease Diseases 0.000 claims abstract description 28
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- 108090000695 Cytokines Proteins 0.000 claims abstract description 23
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 386
- 125000000217 alkyl group Chemical group 0.000 claims description 210
- 239000000203 mixture Substances 0.000 claims description 158
- 150000003839 salts Chemical class 0.000 claims description 107
- 125000000623 heterocyclic group Chemical group 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 239000012453 solvate Substances 0.000 claims description 55
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 125000003118 aryl group Chemical group 0.000 claims description 43
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 43
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 43
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 39
- 229910052736 halogen Inorganic materials 0.000 claims description 39
- 150000002367 halogens Chemical class 0.000 claims description 38
- 238000011282 treatment Methods 0.000 claims description 34
- 102000002569 MAP Kinase Kinase 4 Human genes 0.000 claims description 32
- 108010068304 MAP Kinase Kinase 4 Proteins 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 230000000694 effects Effects 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 230000001404 mediated effect Effects 0.000 claims description 27
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 125000004043 oxo group Chemical group O=* 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 239000003981 vehicle Substances 0.000 claims description 12
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 230000016396 cytokine production Effects 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical group C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 claims description 4
- JIIWFBWSAHKMIA-UHFFFAOYSA-N 3-[[4-[2-(4-fluorophenyl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-yl]amino]propan-1-ol Chemical compound OCCCNC1=NC=CC(C2=C3C=CC(=CN3N=C2C=2C=CC(F)=CC=2)C(F)(F)F)=N1 JIIWFBWSAHKMIA-UHFFFAOYSA-N 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- NAYYNDKKHOIIOD-UHFFFAOYSA-N phthalamide Chemical compound NC(=O)C1=CC=CC=C1C(N)=O NAYYNDKKHOIIOD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims 2
- 238000000034 method Methods 0.000 abstract description 77
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- 150000003217 pyrazoles Chemical class 0.000 abstract description 3
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 abstract description 2
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 abstract description 2
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 abstract description 2
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- 101001045447 Synechocystis sp. (strain PCC 6803 / Kazusa) Sensor histidine kinase Hik2 Proteins 0.000 abstract description 2
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- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 abstract description 2
- 230000036961 partial effect Effects 0.000 abstract description 2
- 239000003909 protein kinase inhibitor Substances 0.000 abstract description 2
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 abstract 1
- 101100481404 Danio rerio tie1 gene Proteins 0.000 abstract 1
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- 238000005481 NMR spectroscopy Methods 0.000 description 119
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
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- 238000006243 chemical reaction Methods 0.000 description 73
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
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- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 38
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 34
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
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- 235000010413 sodium alginate Nutrition 0.000 description 1
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- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-N sodium;2-hydroxybenzoic acid Chemical compound [Na+].OC(=O)C1=CC=CC=C1O ABBQHOQBGMUPJH-UHFFFAOYSA-N 0.000 description 1
- AGHLUVOCTHWMJV-UHFFFAOYSA-J sodium;gold(3+);2-sulfanylbutanedioate Chemical compound [Na+].[Au+3].[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O AGHLUVOCTHWMJV-UHFFFAOYSA-J 0.000 description 1
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- STTXQMXHCRPEOE-UHFFFAOYSA-N tert-butyl [hydroxy-(2,4,6-trimethylphenyl)sulfonylamino] carbonate Chemical compound CC1=CC(C)=C(S(=O)(=O)N(O)OC(=O)OC(C)(C)C)C(C)=C1 STTXQMXHCRPEOE-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
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- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
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- UNEPXPMBVGDXGH-UHFFFAOYSA-N tributyl(pyridin-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=NC=C1 UNEPXPMBVGDXGH-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
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- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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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
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Landscapes
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0020576 | 2000-08-22 | ||
| GB0020576A GB0020576D0 (en) | 2000-08-22 | 2000-08-22 | Fused pyrazole derivatives |
| GB0020556 | 2000-08-22 | ||
| GBGB0020556.7A GB0020556D0 (en) | 2000-08-22 | 2000-08-22 | Fused pyrazole derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2259331T3 true ES2259331T3 (es) | 2006-10-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES01960928T Expired - Lifetime ES2259331T3 (es) | 2000-08-22 | 2001-08-22 | Derivados de pirazol fusionado como inhibidores de la proteina quinasa. |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US7166597B2 (enExample) |
| EP (1) | EP1311507B1 (enExample) |
| JP (1) | JP2004506736A (enExample) |
| KR (1) | KR20030040419A (enExample) |
| AR (1) | AR034261A1 (enExample) |
| AT (1) | ATE318814T1 (enExample) |
| AU (1) | AU2001282318A1 (enExample) |
| BR (1) | BR0113448A (enExample) |
| CA (1) | CA2420024A1 (enExample) |
| DE (1) | DE60117568T2 (enExample) |
| ES (1) | ES2259331T3 (enExample) |
| HU (1) | HUP0400757A2 (enExample) |
| IL (1) | IL154402A0 (enExample) |
| MX (1) | MXPA03001593A (enExample) |
| NO (1) | NO20030779L (enExample) |
| PE (1) | PE20020506A1 (enExample) |
| PL (1) | PL362130A1 (enExample) |
| UY (1) | UY26899A1 (enExample) |
| WO (1) | WO2002016359A1 (enExample) |
Families Citing this family (93)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| DE60112609T2 (de) * | 2000-12-15 | 2006-01-19 | Glaxo Group Ltd., Greenford | Pyrazolopyridine |
| US7163940B2 (en) | 2000-12-15 | 2007-01-16 | Smithkline Beecham Corporation | Pyrazolopyridinyl pyrimidine therapeutic compounds |
| ES2227451T3 (es) * | 2001-03-08 | 2005-04-01 | Smithkline Beecham Corporation | Derivados de pirazolopiridina. |
| JP4237497B2 (ja) | 2001-03-30 | 2009-03-11 | スミスクライン ビーチャム コーポレーション | ピラゾロピリジン類、その調製方法及びその治療用化合物としての使用 |
| GB0108770D0 (en) | 2001-04-06 | 2001-05-30 | Eisai London Res Lab Ltd | Inhibitors |
| WO2002083672A1 (en) * | 2001-04-10 | 2002-10-24 | Smithkline Beecham Corporation | Antiviral pyrazolopyridine compounds |
| EP1385847B1 (en) | 2001-04-27 | 2005-06-01 | SmithKline Beecham Corporation | Pyrazolo[1,5-a]pyridine derivatives |
| SK287857B6 (sk) | 2001-05-24 | 2012-01-04 | Eli Lilly And Company | Novel pyrrole derivatives as pharmaceutical agents |
| IL158667A0 (en) | 2001-06-21 | 2004-05-12 | Smithkline Beecham Corp | Imidazo [1,2-a] pyridine derivatives for the prophylaxis and treatment of herpes viral infections |
| EP1424078A4 (en) * | 2001-09-04 | 2009-03-25 | Ono Pharmaceutical Co | RESPIRATORY DISEASE MEDICINES COMPRISING A SPHINGOSINE-1-PHOSPHATE RECEPTOR REGULATING AGENT |
| ES2262893T3 (es) | 2001-10-05 | 2006-12-01 | Smithkline Beecham Corporation | Derivados de imidazo-piridina para su uso en el tratamiento de infeccion virica por herpes. |
| 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 |
| GB0124941D0 (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 |
| GB0124936D0 (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 |
| US7199120B2 (en) | 2001-12-11 | 2007-04-03 | Smithkline Beecham Corporation | Pyrazolo-pyridine derivatives as antiherpes agents |
| JP4472349B2 (ja) * | 2002-02-12 | 2010-06-02 | スミスクライン ビーチャム コーポレーション | ｐ３８阻害薬として有用なニコチンアミド誘導体 |
| KR20040111445A (ko) | 2002-03-28 | 2004-12-31 | 에자이 가부시키가이샤 | 신경퇴행성 질환 치료용 ｃ─Ｊｕｎ Ｎ─말단 키나아제억제제로서의 ７─아자인돌 |
| US7291630B2 (en) | 2002-03-28 | 2007-11-06 | Eisai Co., Ltd. | Azaindoles as inhibitors of c-Jun N-terminal kinases |
| AR039241A1 (es) | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
| GB0209891D0 (en) * | 2002-04-30 | 2002-06-05 | Glaxo Group Ltd | Novel compounds |
| ES2287476T3 (es) | 2002-05-10 | 2007-12-16 | Smithkline Beecham Corporation | Pirazolopirimidinas sustituidas. |
| MY140680A (en) | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
| GB0217783D0 (en) * | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Compounds |
| GB0217757D0 (en) * | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Novel compounds |
| WO2004013135A1 (en) * | 2002-07-31 | 2004-02-12 | Smithkline Beecham Corporation | 2-phenylpyridin-4-yl derivatives as alk5 inhibitors |
| UA80295C2 (en) * | 2002-09-06 | 2007-09-10 | Biogen Inc | Pyrazolopyridines and using the same |
| CN1681809A (zh) | 2002-09-18 | 2005-10-12 | 辉瑞产品公司 | 作为转化生长因子(tgf)抑制剂的新的异噻唑和异噁唑化合物 |
| PL375979A1 (en) | 2002-09-18 | 2005-12-12 | Pfizer Products Inc. | Pyrazole derivatives as transforming growth factor (tgf) inhibitors |
| HRP20050252A2 (en) | 2002-09-18 | 2005-10-31 | Pfizer Products Inc. | Novel imidazole compounds as transforming growth factor (tfg) inhibitors |
| WO2004026863A1 (en) | 2002-09-18 | 2004-04-01 | Pfizer Products Inc. | Novel oxazole and thiazole compounds as transforming growth factor (tgf) inhibitors |
| AU2003260810A1 (en) | 2002-09-18 | 2004-04-08 | Pfizer Products Inc. | Triazole derivatives as transforming growth factor (tgf) inhibitors |
| US7153863B2 (en) * | 2002-10-03 | 2006-12-26 | Smithkline Beecham Corporation | Therapeutic compounds based on pyrazolopyridline derivatives |
| KR101312736B1 (ko) | 2003-02-27 | 2013-09-27 | 팔라우 파르마 에스에이 | 피라졸로피리딘 유도체 |
| PA8595001A1 (es) | 2003-03-04 | 2004-09-28 | Pfizer Prod Inc | Nuevos compuestos heteroaromaticos condensados que son inhibidores del factor de crecimiento transforante (tgf) |
| GB0305142D0 (en) | 2003-03-06 | 2003-04-09 | Eisai London Res Lab Ltd | Synthesis |
| US7612086B2 (en) | 2003-05-16 | 2009-11-03 | Eisai R & D Management Co. Ltd. | JNK inhibitors |
| SE0301906D0 (sv) * | 2003-06-26 | 2003-06-26 | Astrazeneca Ab | New compounds |
| GB0318814D0 (en) * | 2003-08-11 | 2003-09-10 | Smithkline Beecham Corp | Novel compounds |
| GB0402143D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| GB0402138D0 (en) | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| GB0402140D0 (en) | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| MY143245A (en) * | 2004-04-28 | 2011-04-15 | Mitsubishi Tanabe Pharma Corp | 4- 2-(cycloalkylamino)pyrimidin-4-yl-(phenyl)-imidazolin-2-one derivatives as p38 map-kinase inhibitors for the treatment of inflammatory diseases |
| US7452887B2 (en) * | 2004-06-04 | 2008-11-18 | Amphora Discovery Corporation | Quinoline- and isoquinoline-based compounds exhibiting ATP-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| US20080051416A1 (en) * | 2004-10-05 | 2008-02-28 | Smithkline Beecham Corporation | Novel Compounds |
| WO2006038001A1 (en) * | 2004-10-06 | 2006-04-13 | Celltech R & D Limited | Aminopyrimidine derivatives as jnk inhibitors |
| US7485725B1 (en) * | 2004-11-12 | 2009-02-03 | Frontier Scientific, Inc. | Substituted pyridines |
| US7812022B2 (en) | 2004-12-21 | 2010-10-12 | Glaxosmithkline Llc | 2-pyrimidinyl pyrazolopyridine ErbB kinase inhibitors |
| WO2006068826A2 (en) * | 2004-12-21 | 2006-06-29 | Smithkline Beecham Corporation | 2-pyrimidinyl pyrazolopyridine erbb kinase inhibitors |
| GB0512429D0 (en) * | 2005-06-17 | 2005-07-27 | Smithkline Beecham Corp | Novel compound |
| GB0516156D0 (en) | 2005-08-05 | 2005-09-14 | Eisai London Res Lab Ltd | JNK inhibitors |
| US7807673B2 (en) * | 2005-12-05 | 2010-10-05 | Glaxosmithkline Llc | 2-pyrimidinyl pyrazolopyridine ErbB kinase inhibitors |
| EP1974013A2 (en) | 2005-12-29 | 2008-10-01 | Anthrogenesis Corporation | Improved composition for collecting and preserving placental stem cells and methods of using the composition |
| EP2038279A2 (en) * | 2006-06-06 | 2009-03-25 | Avigen, Inc. | Substituted pyrazolo [1,5- alpha] pyridine compounds and their methods of use |
| UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
| US8158656B2 (en) * | 2008-05-16 | 2012-04-17 | Shenzhen Chipscreen Biosciences Ltd. | 2-indolinone derivatives as multi-target protein kinase inhibitors and histone deacetylase inhibitors |
| EP2924023A1 (en) * | 2008-06-30 | 2015-09-30 | Janssen Pharmaceutica NV | piperidine und piperazine derivativs |
| US8048887B2 (en) | 2008-09-11 | 2011-11-01 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US8198449B2 (en) * | 2008-09-11 | 2012-06-12 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US8293909B2 (en) | 2008-09-11 | 2012-10-23 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US7994171B2 (en) | 2008-09-11 | 2011-08-09 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| NZ596123A (en) * | 2009-05-19 | 2014-08-29 | Dow Agrosciences Llc | Compounds and methods for controlling fungi |
| US8211901B2 (en) | 2009-05-22 | 2012-07-03 | Shenzhen Chipscreen Biosciences Ltd. | Naphthamide derivatives as multi-target protein kinase inhibitors and histone deacetylase inhibitors |
| CN101906076B (zh) | 2009-06-04 | 2013-03-13 | 深圳微芯生物科技有限责任公司 | 作为蛋白激酶抑制剂和组蛋白去乙酰化酶抑制剂的萘酰胺衍生物、其制备方法及应用 |
| WO2010144416A1 (en) * | 2009-06-08 | 2010-12-16 | Gaeta Federico C A | SUBSTITUTED PYRAZOLO [1,5-a] PYRIDINE COMPOUNDS HAVING MULTI-TARGET ACTIVITY |
| US8502789B2 (en) | 2010-01-11 | 2013-08-06 | Smart Technologies Ulc | Method for handling user input in an interactive input system, and interactive input system executing the method |
| EP2360158A1 (en) * | 2010-02-18 | 2011-08-24 | Almirall, S.A. | Pyrazole derivatives as jak inhibitors |
| UY33213A (es) | 2010-02-18 | 2011-09-30 | Almirall Sa | Derivados de pirazol como inhibidores de jak |
| US8324212B2 (en) | 2010-02-25 | 2012-12-04 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US8354410B2 (en) | 2010-03-11 | 2013-01-15 | Bristol-Meyers Squibb Company | Compounds for the treatment of hepatitis C |
| EP2402336A1 (en) | 2010-06-29 | 2012-01-04 | Basf Se | Pyrazolopyridine compounds |
| EP2402335A1 (en) | 2010-06-29 | 2012-01-04 | Basf Se | Pyrazolopyridine compounds |
| US8445497B2 (en) | 2010-06-30 | 2013-05-21 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| EP2463289A1 (en) | 2010-11-26 | 2012-06-13 | Almirall, S.A. | Imidazo[1,2-b]pyridazine derivatives as JAK inhibitors |
| EP2554544A1 (en) | 2011-08-01 | 2013-02-06 | Almirall, S.A. | Pyridin-2(1h)-one derivatives as jak inhibitors |
| WO2013050434A1 (en) * | 2011-10-06 | 2013-04-11 | Bayer Intellectual Property Gmbh | Heterocyclylpyri(mi)dinylpyrazole |
| US9303020B2 (en) | 2012-02-08 | 2016-04-05 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| WO2014078802A1 (en) | 2012-11-19 | 2014-05-22 | Irm Llc | Compounds and compositions for the treatment of parasitic diseases |
| GB201321733D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| SG11201605207PA (en) * | 2013-12-26 | 2016-07-28 | Ignyta Inc | Pyrazolo[1,5-a]pyridine derivatives and methods of their use |
| US20190060286A1 (en) | 2016-02-29 | 2019-02-28 | University Of Florida Research Foundation, Incorpo | Chemotherapeutic Methods |
| EP3464287B1 (en) * | 2016-06-02 | 2022-06-08 | Celgene Corporation | Animal and human anti-malarial agents |
| WO2017210408A1 (en) * | 2016-06-02 | 2017-12-07 | Celgene Corporation | Animal and human anti-trypanosomonal and anti-leishmania agents |
| JP2021501130A (ja) | 2017-10-05 | 2021-01-14 | フルクラム セラピューティクス，インコーポレイテッド | ＤＵＸ４の発現を低減するためのｐ３８阻害剤の使用 |
| 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 |
| CN110563626B (zh) * | 2019-09-04 | 2023-03-10 | 天津中医药大学 | 一种1h-氮杂环丙烯类化合物及其合成方法 |
| EP4660192A1 (en) * | 2020-08-05 | 2025-12-10 | The General Hospital Corporation | Salt inducible kinase inhibitors |
| JP2025532184A (ja) * | 2022-07-29 | 2025-09-29 | ベイラー カレッジ オブ メディスン | 神経栄養因子受容体チロシンキナーゼ（ｎｔｒｋ）阻害剤およびそれを使用する方法 |
Family Cites Families (112)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4200750A (en) * | 1977-01-07 | 1980-04-29 | Westwood Pharmaceuticals Inc. | 4-Substituted imidazo [1,2-a]quinoxalines |
| EP0151962A3 (en) * | 1984-01-25 | 1985-10-02 | Beecham Group Plc | Pyrazolopyridine derivatives |
| GB8404586D0 (en) * | 1984-02-22 | 1984-03-28 | Beecham Group Plc | Compounds |
| GB8404584D0 (en) * | 1984-02-22 | 1984-03-28 | Beecham Group Plc | Compounds |
| US5002941A (en) | 1985-12-12 | 1991-03-26 | Smithkline Beecham Corporation | Pyrrolo(1,2-a)imidazole and imidazo(1,2-a)pyridine derivatives and their use as 5-lipoxygenase pathway inhibitors |
| US4925849A (en) * | 1987-06-15 | 1990-05-15 | Fujisawa Pharmaceutical Company, Ltd. | Pharmaceutically useful pyrazolopyridines |
| US5155114A (en) * | 1989-01-23 | 1992-10-13 | Fujisawa Pharmaceutical Company, Ltd. | Method of treatment using pyrazolopyridine compound |
| EP0346841A3 (de) | 1988-06-16 | 1991-01-09 | Ciba-Geigy Ag | 1-Aryl-naphthoesäureamide und diese enthaltende mikrobizide Mittel |
| GB8901423D0 (en) * | 1989-01-23 | 1989-03-15 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
| JPH05503919A (ja) | 1989-06-13 | 1993-06-24 | スミスクライン・ビーチャム・コーポレイション | 単球および／またはマクロファージによるインターロイキン―１または腫瘍壊死因子生成の抑制 |
| AU622330B2 (en) | 1989-06-23 | 1992-04-02 | Takeda Chemical Industries Ltd. | Condensed heterocyclic compounds having a nitrogen atom in the bridgehead for use as fungicides |
| EP0430033A3 (en) | 1989-11-24 | 1991-09-11 | Ciba-Geigy Ag | Microbicidal agents |
| KR930700104A (ko) | 1990-06-12 | 1993-03-13 | 원본미기재 | 5-리프옥시게나제 및 사이클로옥시게나제 경로 개재된 질병의 억제 |
| GB9015764D0 (en) * | 1990-07-18 | 1990-09-05 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
| CA2060138A1 (en) | 1991-01-29 | 1992-07-30 | Youichi Shiokawa | New use of the adenosine antagonist |
| GB9107513D0 (en) * | 1991-04-10 | 1991-05-29 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
| ES2162792T3 (es) | 1991-09-18 | 2002-01-16 | Glaxo Group Ltd | Derivados de benzanilida como antagonistas de 5-ht1d. |
| GB9119920D0 (en) | 1991-09-18 | 1991-10-30 | Glaxo Group Ltd | Chemical compounds |
| US5246943A (en) * | 1992-05-19 | 1993-09-21 | Warner-Lambert Company | Substituted 1,2,3,4-tetahydroisoquinolines with angiotensin II receptor antagonist properties |
| US5236934A (en) * | 1992-08-26 | 1993-08-17 | E. I. Du Pont De Nemours And Company | 1,2,3,4-tetrahydroisoquinolines useful in the treatment of CNS disorders |
| TW240217B (enExample) | 1992-12-30 | 1995-02-11 | Glaxo Group Ltd | |
| GB2273930A (en) | 1992-12-30 | 1994-07-06 | Glaxo Group Ltd | Benzanilide derivatives |
| US5300478A (en) * | 1993-01-28 | 1994-04-05 | Zeneca Limited | Substituted fused pyrazolo compounds |
| IL108630A0 (en) * | 1993-02-18 | 1994-05-30 | Fmc Corp | Insecticidal substituted 2,4-diaminoquinazolines |
| GB2276162A (en) | 1993-03-17 | 1994-09-21 | Glaxo Group Ltd | Aniline and benazilide derivatives |
| GB2276161A (en) | 1993-03-17 | 1994-09-21 | Glaxo Group Ltd | Aniline and benzanilide derivatives |
| US5474995A (en) | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
| CN1129933A (zh) | 1993-08-31 | 1996-08-28 | 辉瑞大药厂 | 5-芳基吲哚衍生物 |
| WO1995006644A1 (en) | 1993-09-03 | 1995-03-09 | Smithkline Beecham Plc | Amide derivatives as 5ht1d receptor antagonists |
| EP0724580A1 (en) | 1993-10-19 | 1996-08-07 | Smithkline Beecham Plc | Benzanilide derivatives as 5ht-1d receptor antagonists |
| JPH09506101A (ja) | 1993-12-07 | 1997-06-17 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | ５ｈｔ１ｄ拮抗薬として有用な複素環式ビフェニリルアミド類 |
| GB9326008D0 (en) | 1993-12-21 | 1994-02-23 | Smithkline Beecham Plc | Novel compounds |
| GB9408577D0 (en) * | 1994-04-29 | 1994-06-22 | Fujisawa Pharmaceutical Co | New compound |
| JPH09512804A (ja) | 1994-05-06 | 1997-12-22 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | ５−ｈｔ１ｄアンタゴニストとして有用なビフェニルカルボキシアミド類 |
| US5521213A (en) * | 1994-08-29 | 1996-05-28 | Merck Frosst Canada, Inc. | Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2 |
| GB2295387A (en) | 1994-11-23 | 1996-05-29 | Glaxo Inc | Quinazoline antagonists of alpha 1c adrenergic receptors |
| US5552422A (en) * | 1995-01-11 | 1996-09-03 | Merck Frosst Canada, Inc. | Aryl substituted 5,5 fused aromatic nitrogen compounds as anti-inflammatory agents |
| EP0819127A1 (en) * | 1995-04-04 | 1998-01-21 | Glaxo Group Limited | IMIDAZO [1,2-a]PYRIDINE DERIVATIVES |
| GB9507203D0 (en) | 1995-04-07 | 1995-05-31 | Smithkline Beecham Plc | Novel compounds |
| US5658903A (en) * | 1995-06-07 | 1997-08-19 | Smithkline Beecham Corporation | Imidazole compounds, compositions and use |
| ATE301457T1 (de) * | 1995-06-12 | 2005-08-15 | Searle & Co | Mittel, enthaltend einen cyclooxygenase-2 inhibitor und einen 5-lipoxygenase inhibitor |
| EP0833664A1 (en) | 1995-06-12 | 1998-04-08 | G.D. SEARLE & CO. | Combination of a cyclooxygenase-2 inhibitor and a leukotriene b 4? receptor antagonist for the treatment of inflammations |
| US5700816A (en) | 1995-06-12 | 1997-12-23 | Isakson; Peter C. | Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor |
| CA2226849A1 (en) | 1995-07-10 | 1997-01-30 | Zenon Lysenko | Stable polynitrile oxides and their use as curing agent especially for latex |
| EP1304322A3 (en) * | 1995-08-22 | 2003-11-19 | Japan Tobacco Inc. | Carboxylic acid compound and use thereof |
| ES2205167T3 (es) * | 1996-01-11 | 2004-05-01 | Smithkline Beecham Corporation | Nuevos compuestos de imidazol sustituidos. |
| FR2757059B1 (fr) | 1996-12-12 | 1999-01-29 | Rhone Poulenc Rorer Sa | Nouvelle application therapeutique des derives du pyrrole |
| FR2757166B1 (fr) * | 1996-12-12 | 1999-01-29 | Rhone Poulenc Rorer Sa | Derives du pyrrole, leur preparation et les compositions pharmaceutiques qui les contiennent |
| US6147080A (en) * | 1996-12-18 | 2000-11-14 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| US5945418A (en) * | 1996-12-18 | 1999-08-31 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| AU7132998A (en) * | 1997-04-24 | 1998-11-13 | Ortho-Mcneil Corporation, Inc. | Substituted pyrrolopyridines useful in the treatment of inflammatory diseases |
| US6087496A (en) * | 1998-05-22 | 2000-07-11 | G. D. Searle & Co. | Substituted pyrazoles suitable as p38 kinase inhibitors |
| PL336990A1 (en) * | 1997-05-22 | 2000-07-31 | Searle & Co | 3(5)-heteroaryl group substituted pyrazoles as inhibitors of kinase p 38 |
| EP1023066A4 (en) * | 1997-06-13 | 2001-05-23 | Smithkline Beecham Corp | NEW PYRAZOLE AND PYRAZOLINE SUBSTITUTED COMPOUND |
| US6251914B1 (en) * | 1997-07-02 | 2001-06-26 | Smithkline Beecham Corporation | Cycloalkyl substituted imidazoles |
| CA2303152A1 (en) * | 1997-09-05 | 1999-03-18 | Glaxo Group Limited | 2,3-diaryl-pyrazolo[1,5-b]pyridazines derivatives, their preparation and their use as cyclooxygenase 2 (cox-2) inhibitors |
| IL136737A0 (en) | 1997-12-22 | 2001-06-14 | Bayer Ag | Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas |
| DE19817461A1 (de) * | 1998-04-20 | 1999-10-21 | Basf Ag | Neue substituierte Benzamide, deren Herstellung und Anwendung |
| EP1077971A1 (en) * | 1998-05-14 | 2001-02-28 | G.D. SEARLE & CO. | 1,5-DIARYL SUBSTITUTED PYRAZOLES AS p38 KINASE INHIBITORS |
| ATE282590T1 (de) * | 1998-05-15 | 2004-12-15 | Astrazeneca Ab | Benzamid-derivate zur behandlung cytokin- vermittelter krankheiten |
| US6245789B1 (en) | 1998-05-19 | 2001-06-12 | The Procter & Gamble Company | HIV and viral treatment |
| US6130235A (en) * | 1998-05-22 | 2000-10-10 | Scios Inc. | Compounds and methods to treat cardiac failure and other disorders |
| FR2779724B1 (fr) | 1998-06-10 | 2001-04-20 | Rhone Poulenc Rorer Sa | Derives du pyrrole, leur preparation et les compositions pharmaceutiques qui les contiennent |
| IL141724A0 (en) | 1998-08-28 | 2002-03-10 | Scios Inc | INHIBITORS OF P38-α KINASE |
| US6184226B1 (en) * | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| JP2002526482A (ja) * | 1998-09-18 | 2002-08-20 | 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 |
| CN1263755C (zh) * | 1998-11-03 | 2006-07-12 | 葛兰素集团有限公司 | 作为选择性cox－2抑制剂的吡唑并吡啶衍生物 |
| WO2000039116A1 (en) * | 1998-12-25 | 2000-07-06 | Teikoku Hormone Mfg. Co., Ltd. | Aminopyrazole derivatives |
| EP1140840B1 (en) * | 1999-01-13 | 2006-03-22 | Bayer Pharmaceuticals Corp. | -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| DE69915519T2 (de) | 1999-02-27 | 2005-02-03 | Glaxo Group Ltd., Greenford | Pyrazolopyridine |
| GB9906566D0 (en) | 1999-03-23 | 1999-05-19 | Zeneca Ltd | Chemical compounds |
| US6509361B1 (en) * | 1999-05-12 | 2003-01-21 | Pharmacia Corporation | 1,5-Diaryl substituted pyrazoles as p38 kinase inhibitors |
| CA2374820A1 (en) | 1999-05-24 | 2000-11-30 | Cor Therapeutics, Inc. | Inhibitors of factor xa |
| JP2003500376A (ja) | 1999-05-24 | 2003-01-07 | シーオーアール セラピューティクス インコーポレイテッド | Ｘａ因子の阻害剤 |
| JP2003500386A (ja) * | 1999-05-24 | 2003-01-07 | シーオーアール セラピューティクス インコーポレイテッド | Ｘａ因子阻害剤 |
| CZ20014573A3 (cs) | 1999-06-28 | 2002-05-15 | Janssen Pharmaceutica N. V. | Inhibitory replikace respiračně syncyciálního viru |
| GB9919778D0 (en) * | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| GB9924092D0 (en) | 1999-10-13 | 1999-12-15 | Zeneca Ltd | Pyrimidine derivatives |
| MXPA01007019A (es) | 1999-11-10 | 2002-09-18 | Johnson & Johnson | 2-aril-3-(heteroaril)-imidazo[1,2-a]pirimidinas, sustituidas y composiciones farmaceuticas relacionados y metodos. |
| WO2001070695A1 (en) | 2000-03-22 | 2001-09-27 | Vertex Pharmaceuticals Incorporated | Pyridine derivatives as inhibitors of p38 |
| AU2001259242A1 (en) | 2000-04-28 | 2001-11-12 | Glaxo Group Limited | Process for the preparation of chemical compounds |
| EP1283208A4 (en) | 2000-05-18 | 2003-08-13 | Daiichi Seiyaku Co | NEW BENZOFURAN DERIVATIVES |
| PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| AUPQ969800A0 (en) | 2000-08-28 | 2000-09-21 | Fujisawa Pharmaceutical Co., Ltd. | Pyrazolopyridine compound and pharmaceutical use thereof |
| DK1363910T3 (da) | 2000-11-17 | 2006-06-26 | Bristol Myers Squibb Co | Fremgangsmåder til behandling af P39-kinase-associerede tilstande og pyrrolotriazinforbindelser, der er anvendelige som kinase-inhibitorer |
| US7163940B2 (en) | 2000-12-15 | 2007-01-16 | Smithkline Beecham Corporation | Pyrazolopyridinyl pyrimidine therapeutic compounds |
| DE60112609T2 (de) * | 2000-12-15 | 2006-01-19 | Glaxo Group Ltd., Greenford | Pyrazolopyridine |
| DE10063008A1 (de) | 2000-12-16 | 2002-06-20 | Merck Patent Gmbh | Carbonsäureamidderivate |
| GB0103926D0 (en) | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| DE10110749A1 (de) * | 2001-03-07 | 2002-09-12 | Bayer Ag | Substituierte Aminodicarbonsäurederivate |
| US6756498B2 (en) * | 2001-04-27 | 2004-06-29 | Smithkline Beecham Corporation | Process for the preparation of chemical compounds |
| EP1385847B1 (en) * | 2001-04-27 | 2005-06-01 | SmithKline Beecham Corporation | Pyrazolo[1,5-a]pyridine derivatives |
| US7196095B2 (en) | 2001-06-25 | 2007-03-27 | Merck & Co., Inc. | (Pyrimidinyl) (phenyl) substituted fused heteroaryl p38 inhibiting and PKG kinase inhibiting compounds |
| GB0124939D0 (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 |
| GB0124932D0 (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 |
| GB0124928D0 (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 |
| GB0124941D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| JP4472349B2 (ja) | 2002-02-12 | 2010-06-02 | スミスクライン ビーチャム コーポレーション | ｐ３８阻害薬として有用なニコチンアミド誘導体 |
| GB0209891D0 (en) | 2002-04-30 | 2002-06-05 | Glaxo Group Ltd | Novel compounds |
| GB0217757D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Novel compounds |
| US20040038014A1 (en) * | 2002-08-20 | 2004-02-26 | Donaldson Company, Inc. | Fiber containing filter media |
| GB0308185D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| 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 |
| MXPA06000915A (es) * | 2003-07-25 | 2006-03-30 | Novartis Ag | Inhibidores de quinasa p-38. |
| GB0318814D0 (en) | 2003-08-11 | 2003-09-10 | Smithkline Beecham Corp | Novel compounds |
| GB0329572D0 (en) | 2003-12-20 | 2004-01-28 | Astrazeneca Ab | Amide derivatives |
-
2001
- 2001-08-21 PE PE2001000842A patent/PE20020506A1/es not_active Application Discontinuation
- 2001-08-22 BR BR0113448-5A patent/BR0113448A/pt not_active Application Discontinuation
- 2001-08-22 JP JP2002521460A patent/JP2004506736A/ja active Pending
- 2001-08-22 HU HU0400757A patent/HUP0400757A2/hu unknown
- 2001-08-22 AR ARP010104007A patent/AR034261A1/es unknown
- 2001-08-22 DE DE60117568T patent/DE60117568T2/de not_active Expired - Fee Related
- 2001-08-22 PL PL36213001A patent/PL362130A1/xx not_active Application Discontinuation
- 2001-08-22 EP EP01960928A patent/EP1311507B1/en not_active Expired - Lifetime
- 2001-08-22 MX MXPA03001593A patent/MXPA03001593A/es unknown
- 2001-08-22 WO PCT/GB2001/003783 patent/WO2002016359A1/en not_active Ceased
- 2001-08-22 IL IL15440201A patent/IL154402A0/xx unknown
- 2001-08-22 KR KR10-2003-7002634A patent/KR20030040419A/ko not_active Withdrawn
- 2001-08-22 UY UY26899A patent/UY26899A1/es unknown
- 2001-08-22 AU AU2001282318A patent/AU2001282318A1/en not_active Abandoned
- 2001-08-22 AT AT01960928T patent/ATE318814T1/de not_active IP Right Cessation
- 2001-08-22 US US10/362,146 patent/US7166597B2/en not_active Expired - Fee Related
- 2001-08-22 CA CA002420024A patent/CA2420024A1/en not_active Abandoned
- 2001-08-22 ES ES01960928T patent/ES2259331T3/es not_active Expired - Lifetime
-
2003
- 2003-02-19 NO NO20030779A patent/NO20030779L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| DE60117568T2 (de) | 2006-08-24 |
| IL154402A0 (en) | 2003-09-17 |
| AR034261A1 (es) | 2004-02-18 |
| UY26899A1 (es) | 2002-03-22 |
| CA2420024A1 (en) | 2002-02-28 |
| KR20030040419A (ko) | 2003-05-22 |
| AU2001282318A1 (en) | 2002-03-04 |
| MXPA03001593A (es) | 2003-06-04 |
| EP1311507A1 (en) | 2003-05-21 |
| PL362130A1 (en) | 2004-10-18 |
| ATE318814T1 (de) | 2006-03-15 |
| DE60117568D1 (de) | 2006-04-27 |
| WO2002016359A1 (en) | 2002-02-28 |
| NO20030779D0 (no) | 2003-02-19 |
| JP2004506736A (ja) | 2004-03-04 |
| EP1311507B1 (en) | 2006-03-01 |
| US7166597B2 (en) | 2007-01-23 |
| BR0113448A (pt) | 2003-06-17 |
| PE20020506A1 (es) | 2002-07-09 |
| HUP0400757A2 (hu) | 2004-07-28 |
| US20040053942A1 (en) | 2004-03-18 |
| NO20030779L (no) | 2003-04-07 |
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