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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- 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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- 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
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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
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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 |
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| GB0020576 | 2000-08-22 | ||
| GB0020556 | 2000-08-22 | ||
| GBGB0020556.7A GB0020556D0 (en) | 2000-08-22 | 2000-08-22 | Fused pyrazole derivatives |
| GB0020576A GB0020576D0 (en) | 2000-08-22 | 2000-08-22 | Fused pyrazole derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2259331T3 true ES2259331T3 (es) | 2006-10-01 |
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| ES01960928T Expired - Lifetime ES2259331T3 (es) | 2000-08-22 | 2001-08-22 | Derivados de pirazol fusionado como inhibidores de la proteina quinasa. |
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| PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| ES2245380T3 (es) | 2000-12-15 | 2006-01-01 | Glaxo Group Limited | Pirazolopiridinas. |
| DE60112330T2 (de) | 2000-12-15 | 2006-04-13 | Glaxo Group Ltd., Greenford | Pyrazolopyridinderivate |
| US7153855B2 (en) | 2001-03-08 | 2006-12-26 | Smithkline Beecham Corporation | Pyrazolopyridinyl pyrimidine therapeutic compounds |
| US7034030B2 (en) | 2001-03-30 | 2006-04-25 | Smithkline Beecham Corporation | Pyralopyridines, process for their preparation and use as therapeutic compounds |
| GB0108770D0 (en) | 2001-04-06 | 2001-05-30 | Eisai London Res Lab Ltd | Inhibitors |
| ATE332301T1 (de) | 2001-04-10 | 2006-07-15 | Smithkline Beecham Corp | Antivirale pyrazolopyridin verbindungen |
| US6962914B2 (en) | 2001-04-27 | 2005-11-08 | Smithkline Beecham Corporation | Pyrazolopyridinyl pyridine and pyrimidine therapeutic compounds |
| SK287857B6 (sk) | 2001-05-24 | 2012-01-04 | Eli Lilly And Company | Novel pyrrole derivatives as pharmaceutical agents |
| DE60214179T2 (de) | 2001-06-21 | 2007-01-04 | Smithkline Beecham Corp. | Imidazo-1,2-A/Pyriden-Derivate zur Prophylaxe und Behandlung von Herpes-Infektionen |
| JPWO2003020313A1 (ja) * | 2001-09-04 | 2004-12-16 | 小野薬品工業株式会社 | スフィンゴシン−１−リン酸受容体調節剤からなる呼吸器疾患治療剤 |
| 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. |
| GB0124936D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
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| GB0124931D0 (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 |
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| 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 |
| US6962914B2 (en) * | 2001-04-27 | 2005-11-08 | Smithkline Beecham Corporation | Pyrazolopyridinyl pyridine and pyrimidine therapeutic compounds |
| US6756498B2 (en) | 2001-04-27 | 2004-06-29 | Smithkline Beecham Corporation | Process for the preparation of chemical compounds |
| CA2450555A1 (en) | 2001-06-25 | 2003-01-03 | Merck & Co., Inc. | (pyrimidyl)(phenyl)substituted fused heteroaryl p38 inhibiting and pkg kinase inhibiting compounds |
| GB0124931D0 (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 |
| GB0124933D0 (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 |
| GB0124928D0 (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 |
| ATE375980T1 (de) | 2002-02-12 | 2007-11-15 | Smithkline Beecham Corp | Nicotinamide und deren verwendung als p38 inhibitoren |
| 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 |
| 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 |
| GB0308201D0 (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 JP JP2002521460A patent/JP2004506736A/ja active Pending
- 2001-08-22 EP EP01960928A patent/EP1311507B1/en not_active Expired - Lifetime
- 2001-08-22 KR KR10-2003-7002634A patent/KR20030040419A/ko not_active Withdrawn
- 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 WO PCT/GB2001/003783 patent/WO2002016359A1/en not_active Ceased
- 2001-08-22 MX MXPA03001593A patent/MXPA03001593A/es unknown
- 2001-08-22 CA CA002420024A patent/CA2420024A1/en not_active Abandoned
- 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 HU HU0400757A patent/HUP0400757A2/hu unknown
- 2001-08-22 IL IL15440201A patent/IL154402A0/xx unknown
- 2001-08-22 BR BR0113448-5A patent/BR0113448A/pt not_active Application Discontinuation
- 2001-08-22 US US10/362,146 patent/US7166597B2/en not_active Expired - Fee Related
- 2001-08-22 UY UY26899A patent/UY26899A1/es unknown
- 2001-08-22 AR ARP010104007A patent/AR034261A1/es unknown
- 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 |
|---|---|
| US20040053942A1 (en) | 2004-03-18 |
| WO2002016359A1 (en) | 2002-02-28 |
| HUP0400757A2 (hu) | 2004-07-28 |
| EP1311507B1 (en) | 2006-03-01 |
| IL154402A0 (en) | 2003-09-17 |
| BR0113448A (pt) | 2003-06-17 |
| PE20020506A1 (es) | 2002-07-09 |
| NO20030779D0 (no) | 2003-02-19 |
| NO20030779L (no) | 2003-04-07 |
| EP1311507A1 (en) | 2003-05-21 |
| CA2420024A1 (en) | 2002-02-28 |
| AR034261A1 (es) | 2004-02-18 |
| AU2001282318A1 (en) | 2002-03-04 |
| UY26899A1 (es) | 2002-03-22 |
| ATE318814T1 (de) | 2006-03-15 |
| MXPA03001593A (es) | 2003-06-04 |
| US7166597B2 (en) | 2007-01-23 |
| DE60117568T2 (de) | 2006-08-24 |
| JP2004506736A (ja) | 2004-03-04 |
| PL362130A1 (en) | 2004-10-18 |
| KR20030040419A (ko) | 2003-05-22 |
| DE60117568D1 (de) | 2006-04-27 |
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