AU2003294830B2 - Pyridino `2, 3-D! pyrimidine derivatives as selective KDR and FGFR inhibitors - Google Patents
Pyridino `2, 3-D! pyrimidine derivatives as selective KDR and FGFR inhibitors Download PDFInfo
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- AU2003294830B2 AU2003294830B2 AU2003294830A AU2003294830A AU2003294830B2 AU 2003294830 B2 AU2003294830 B2 AU 2003294830B2 AU 2003294830 A AU2003294830 A AU 2003294830A AU 2003294830 A AU2003294830 A AU 2003294830A AU 2003294830 B2 AU2003294830 B2 AU 2003294830B2
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- Prior art keywords
- substituted
- lower alkyl
- phenyl
- pyrimidin
- cor
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- 108091008794 FGF receptors Proteins 0.000 title claims description 11
- 239000003112 inhibitor Substances 0.000 title description 10
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 title 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title 1
- 150000003230 pyrimidines Chemical class 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims description 126
- 150000001875 compounds Chemical class 0.000 claims description 67
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims description 53
- 125000005842 heteroatom Chemical group 0.000 claims description 50
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 48
- 125000003545 alkoxy group Chemical group 0.000 claims description 46
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 150000002367 halogens Chemical class 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 18
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 15
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 11
- -1 Cyclopropylmethyl-6-(4-methoxy-phenyl)-2-phenylamino-5,8-dihydro-6H-pyrid o[2,3-d]pyrimidine-7-one Chemical compound 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 150000004702 methyl esters Chemical class 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- LDBUGKOPMCHTDP-UHFFFAOYSA-N 2-anilino-6,8-diphenyl-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C=3C=CC=CC=3)C(=O)C(C=3C=CC=CC=3)CC2=CN=C1NC1=CC=CC=C1 LDBUGKOPMCHTDP-UHFFFAOYSA-N 0.000 claims description 4
- JRQIBVOYUXEJIW-UHFFFAOYSA-N 2-anilino-6-(2,5-dimethoxyphenyl)-8-phenyl-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound COC1=CC=C(OC)C(C2C(N(C3=NC(NC=4C=CC=CC=4)=NC=C3C2)C=2C=CC=CC=2)=O)=C1 JRQIBVOYUXEJIW-UHFFFAOYSA-N 0.000 claims description 4
- GIGAZROYAJXXTN-UHFFFAOYSA-N 2-anilino-6-(2,6-dichlorophenyl)-8-phenyl-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound ClC1=CC=CC(Cl)=C1C1C(=O)N(C=2C=CC=CC=2)C2=NC(NC=3C=CC=CC=3)=NC=C2C1 GIGAZROYAJXXTN-UHFFFAOYSA-N 0.000 claims description 4
- HNJCPWULRKXSLE-UHFFFAOYSA-N 2-anilino-6-(4-methoxyphenyl)-8-(2-methylpropyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound C1=CC(OC)=CC=C1C1C(=O)N(CC(C)C)C2=NC(NC=3C=CC=CC=3)=NC=C2C1 HNJCPWULRKXSLE-UHFFFAOYSA-N 0.000 claims description 4
- QEAQQVNPEOCGOV-UHFFFAOYSA-N 2-anilino-8-phenyl-6-pyridin-3-yl-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C=3C=CC=CC=3)C(=O)C(C=3C=NC=CC=3)CC2=CN=C1NC1=CC=CC=C1 QEAQQVNPEOCGOV-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- SWSOUWONGSCLAO-UHFFFAOYSA-N ethyl 3-(2,4-dichloropyrimidin-5-yl)-2-(2,5-dimethoxyphenyl)propanoate Chemical compound C=1C(OC)=CC=C(OC)C=1C(C(=O)OCC)CC1=CN=C(Cl)N=C1Cl SWSOUWONGSCLAO-UHFFFAOYSA-N 0.000 claims description 4
- IWFGEGPRCZYRBC-UHFFFAOYSA-N ethyl 3-(2,4-dichloropyrimidin-5-yl)-2-pyridin-4-ylpropanoate Chemical compound C=1C=NC=CC=1C(C(=O)OCC)CC1=CN=C(Cl)N=C1Cl IWFGEGPRCZYRBC-UHFFFAOYSA-N 0.000 claims description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- TVFFUJKYOVNIPR-UHFFFAOYSA-N methyl 2-(2,6-dichlorophenyl)-3-(2,4-dichloropyrimidin-5-yl)propanoate Chemical compound ClC=1C=CC=C(Cl)C=1C(C(=O)OC)CC1=CN=C(Cl)N=C1Cl TVFFUJKYOVNIPR-UHFFFAOYSA-N 0.000 claims description 4
- XMWRLCCDUVRRBL-UHFFFAOYSA-N methyl 2-[3,5-bis(trifluoromethyl)phenyl]-3-(2,4-dianilinopyrimidin-5-yl)propanoate Chemical compound C=1C(C(F)(F)F)=CC(C(F)(F)F)=CC=1C(C(=O)OC)CC(C(=N1)NC=2C=CC=CC=2)=CN=C1NC1=CC=CC=C1 XMWRLCCDUVRRBL-UHFFFAOYSA-N 0.000 claims description 4
- UHPDMTRIBIJMNL-UHFFFAOYSA-N methyl 2-[3,5-bis(trifluoromethyl)phenyl]-3-(2,4-dichloropyrimidin-5-yl)propanoate Chemical compound C=1C(C(F)(F)F)=CC(C(F)(F)F)=CC=1C(C(=O)OC)CC1=CN=C(Cl)N=C1Cl UHPDMTRIBIJMNL-UHFFFAOYSA-N 0.000 claims description 4
- KMZUGCAUUGYOML-UHFFFAOYSA-N methyl 3-(2,4-dianilinopyrimidin-5-yl)-2-(2,6-dichlorophenyl)propanoate Chemical compound ClC=1C=CC=C(Cl)C=1C(C(=O)OC)CC(C(=N1)NC=2C=CC=CC=2)=CN=C1NC1=CC=CC=C1 KMZUGCAUUGYOML-UHFFFAOYSA-N 0.000 claims description 4
- NEBYSCFBTIUOES-UHFFFAOYSA-N methyl 3-(2,4-dianilinopyrimidin-5-yl)-2-(3,5-dimethoxyphenyl)propanoate Chemical compound C=1C(OC)=CC(OC)=CC=1C(C(=O)OC)CC(C(=N1)NC=2C=CC=CC=2)=CN=C1NC1=CC=CC=C1 NEBYSCFBTIUOES-UHFFFAOYSA-N 0.000 claims description 4
- TUSYAGWZCITOPM-UHFFFAOYSA-N methyl 3-(2,4-dichloropyrimidin-5-yl)-2-(4-methoxyphenyl)propanoate Chemical compound C=1C=C(OC)C=CC=1C(C(=O)OC)CC1=CN=C(Cl)N=C1Cl TUSYAGWZCITOPM-UHFFFAOYSA-N 0.000 claims description 4
- BBUHOXYFMXFEHO-UHFFFAOYSA-N methyl 3-(2,4-dichloropyrimidin-5-yl)-2-phenylpropanoate Chemical compound C=1C=CC=CC=1C(C(=O)OC)CC1=CN=C(Cl)N=C1Cl BBUHOXYFMXFEHO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
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- JVJSOURCIHXXBR-UHFFFAOYSA-N ethyl 3-(2,4-dianilinopyrimidin-5-yl)-2-pyridin-4-ylpropanoate Chemical compound C=1C=NC=CC=1C(C(=O)OCC)CC(C(=N1)NC=2C=CC=CC=2)=CN=C1NC1=CC=CC=C1 JVJSOURCIHXXBR-UHFFFAOYSA-N 0.000 claims description 3
- JHDXAYZLXGIVIS-UHFFFAOYSA-N ethyl 3-(2,4-dichloropyrimidin-5-yl)-2-(3,4-dimethoxyphenyl)propanoate Chemical compound C=1C=C(OC)C(OC)=CC=1C(C(=O)OCC)CC1=CN=C(Cl)N=C1Cl JHDXAYZLXGIVIS-UHFFFAOYSA-N 0.000 claims description 3
- LFECLVXEHCFTCS-UHFFFAOYSA-N ethyl 3-(2,4-dichloropyrimidin-5-yl)-2-pyridin-3-ylpropanoate Chemical compound C=1C=CN=CC=1C(C(=O)OCC)CC1=CN=C(Cl)N=C1Cl LFECLVXEHCFTCS-UHFFFAOYSA-N 0.000 claims description 3
- SDXRQYLJBJOROB-UHFFFAOYSA-N methyl 3-(2,4-dianilinopyrimidin-5-yl)-2-phenylpropanoate Chemical compound C=1C=CC=CC=1C(C(=O)OC)CC(C(=N1)NC=2C=CC=CC=2)=CN=C1NC1=CC=CC=C1 SDXRQYLJBJOROB-UHFFFAOYSA-N 0.000 claims description 3
- JSSPHNSXBHHLIE-UHFFFAOYSA-N methyl 3-(2,4-dichloropyrimidin-5-yl)-2-(2-methoxyphenyl)propanoate Chemical compound C=1C=CC=C(OC)C=1C(C(=O)OC)CC1=CN=C(Cl)N=C1Cl JSSPHNSXBHHLIE-UHFFFAOYSA-N 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- IEPKYYKIHJSXQJ-UHFFFAOYSA-N 6,8-dihydro-5h-pyrido[2,3-d]pyrimidin-7-one Chemical class N1=CN=C2NC(=O)CCC2=C1 IEPKYYKIHJSXQJ-UHFFFAOYSA-N 0.000 claims description 2
- PZASAAIJIFDWSB-CKPDSHCKSA-N 8-[(1S)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound FC(F)(F)C=1C2=CC([C@@H](N3C4CCC3CC(C4)C(O)=O)C)=CC=C2C=CC=1OC1CCC(C(F)(F)F)CC1 PZASAAIJIFDWSB-CKPDSHCKSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—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
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
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| US60/434,969 | 2002-12-20 | ||
| US51361503P | 2003-10-23 | 2003-10-23 | |
| US60/513,615 | 2003-10-23 | ||
| PCT/EP2003/014067 WO2004056822A1 (en) | 2002-12-20 | 2003-12-11 | Pyridino `2, 3-d! pyrimidine derivatives as selective kdr and fgfr inhibitors |
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| AU2003294830A1 AU2003294830A1 (en) | 2004-07-14 |
| AU2003294830B2 true AU2003294830B2 (en) | 2009-06-11 |
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| AU2003294830A Expired - Fee Related AU2003294830B2 (en) | 2002-12-20 | 2003-12-11 | Pyridino `2, 3-D! pyrimidine derivatives as selective KDR and FGFR inhibitors |
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| EP (1) | EP1581531B1 (enExample) |
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| AR (1) | AR042532A1 (enExample) |
| AT (1) | ATE387445T1 (enExample) |
| AU (1) | AU2003294830B2 (enExample) |
| BR (1) | BR0317480A (enExample) |
| CA (1) | CA2508951A1 (enExample) |
| DE (1) | DE60319430T2 (enExample) |
| ES (1) | ES2300639T3 (enExample) |
| MX (1) | MXPA05006437A (enExample) |
| PL (1) | PL377661A1 (enExample) |
| RU (1) | RU2345077C2 (enExample) |
| WO (1) | WO2004056822A1 (enExample) |
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| TWI329105B (en) * | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| ES2445208T3 (es) * | 2002-07-29 | 2014-02-28 | Rigel Pharmaceuticals, Inc. | Compuestos de 2,4-pirimidindiamina para uso en métodos para tratar o prevenir enfermedades autoinmunitarias |
| PT1656372E (pt) * | 2003-07-30 | 2013-06-27 | Rigel Pharmaceuticals Inc | Métodos para o tratamento ou prevenção de doenças autoimunes com compostos de 2,4-pirimidinadiamina |
| US20080255162A1 (en) * | 2004-05-04 | 2008-10-16 | Warner-Lambert Company Llc | Pyrrolyl Substituted Pyrido[2,3-D]Pyrimidin-7-Ones and Derivatives Thereof as Therapeutic Agents |
| JP5095409B2 (ja) * | 2004-11-24 | 2012-12-12 | ライジェル ファーマシューティカルズ， インコーポレイテッド | スピロ２，４−ピリミジンジアミン化合物およびその使用 |
| US20060270694A1 (en) * | 2005-05-03 | 2006-11-30 | Rigel Pharmaceuticals, Inc. | JAK kinase inhibitors and their uses |
| EP2018167A4 (en) * | 2006-05-15 | 2010-07-14 | Irm Llc | COMPOSITIONS AND METHODS AS INHIBITORS OF FGF RECEPTOR KINASES |
| KR101099926B1 (ko) * | 2006-09-15 | 2011-12-28 | 화이자 프로덕츠 인코포레이티드 | 피리도 (2,3-ｄ) 피리미디논 화합물 및 이의 ｐｉ3 억제제로서의 용도 |
| GB201007286D0 (en) | 2010-04-30 | 2010-06-16 | Astex Therapeutics Ltd | New compounds |
| GB201020179D0 (en) | 2010-11-29 | 2011-01-12 | Astex Therapeutics Ltd | New compounds |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| GB201118675D0 (en) | 2011-10-28 | 2011-12-14 | Astex Therapeutics Ltd | New compounds |
| GB201118656D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| GB201118654D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| GB201118652D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| GB201209613D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
| GB201209609D0 (en) * | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
| BR112014030812B1 (pt) | 2012-06-13 | 2022-11-08 | Incyte Holdings Corporation | Compostos tricíclicos substituídos como inibidores de fgfr, seus usos, composição farmacêutica e método para inibir uma enzima fgfr |
| WO2014026125A1 (en) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Pyrazine derivatives as fgfr inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| AR094812A1 (es) | 2013-02-20 | 2015-08-26 | Eisai R&D Man Co Ltd | Derivado de piridina monocíclico como inhibidor del fgfr |
| AR095464A1 (es) | 2013-03-15 | 2015-10-21 | Celgene Avilomics Res Inc | Compuestos de heteroarilo y usos de los mismos |
| KR102350704B1 (ko) | 2013-03-15 | 2022-01-13 | 셀젠 카르 엘엘씨 | 헤테로아릴 화합물 및 이의 용도 |
| EA036160B1 (ru) * | 2013-03-15 | 2020-10-08 | Селджен Кар Ллс | Гетероарильные соединения и их применение |
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| NZ296456A (en) * | 1994-11-14 | 1999-09-29 | Warner Lambert Co | 6-aryl pyrido[2,3-d]pyrimidines and naphthyridines; inhibition of protein tyrosine kinase mediated cellular proliferation |
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| WO2002012237A2 (en) | 2000-08-04 | 2002-02-14 | Warner-Lambert Company | Process for preparing 2-(4-pyridyl)amino-6-dialkyloxyphenyl-pyrido[2,3-d]pyrimidin-7-ones |
| ATE408613T1 (de) | 2000-08-04 | 2008-10-15 | Warner Lambert Co | 2-(4-pyridyl)amino-6-dialkoxyphenyl-pyrido(2,3- d)pyrimidin-7-one |
| CA2420286A1 (en) | 2000-08-31 | 2002-03-07 | F. Hoffmann-La Roche Ag | 7-oxo pyridopyrimidines as inhibitors of a cellular proliferation |
| WO2002070662A2 (en) * | 2001-03-02 | 2002-09-12 | Gpc Biotech Ag | Three hybrid assay system |
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2003
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- 2003-12-11 AU AU2003294830A patent/AU2003294830B2/en not_active Expired - Fee Related
- 2003-12-11 MX MXPA05006437A patent/MXPA05006437A/es active IP Right Grant
- 2003-12-11 ES ES03785789T patent/ES2300639T3/es not_active Expired - Lifetime
- 2003-12-11 KR KR1020057011681A patent/KR100763298B1/ko not_active Expired - Fee Related
- 2003-12-11 PL PL377661A patent/PL377661A1/pl not_active Application Discontinuation
- 2003-12-11 CA CA002508951A patent/CA2508951A1/en not_active Abandoned
- 2003-12-11 BR BR0317480-8A patent/BR0317480A/pt not_active IP Right Cessation
- 2003-12-11 JP JP2004561276A patent/JP2006511563A/ja active Pending
- 2003-12-11 AT AT03785789T patent/ATE387445T1/de not_active IP Right Cessation
- 2003-12-11 EP EP03785789A patent/EP1581531B1/en not_active Expired - Lifetime
- 2003-12-11 WO PCT/EP2003/014067 patent/WO2004056822A1/en not_active Ceased
- 2003-12-11 DE DE60319430T patent/DE60319430T2/de not_active Expired - Lifetime
- 2003-12-11 RU RU2005122901/04A patent/RU2345077C2/ru not_active IP Right Cessation
- 2003-12-18 AR ARP030104711A patent/AR042532A1/es unknown
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| RU2345077C2 (ru) | 2009-01-27 |
| US20040122029A1 (en) | 2004-06-24 |
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| JP2006511563A (ja) | 2006-04-06 |
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| EP1581531B1 (en) | 2008-02-27 |
| KR100763298B1 (ko) | 2007-10-04 |
| ES2300639T3 (es) | 2008-06-16 |
| AR042532A1 (es) | 2005-06-22 |
| KR20050088202A (ko) | 2005-09-02 |
| BR0317480A (pt) | 2005-11-16 |
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| EP1581531A1 (en) | 2005-10-05 |
| DE60319430D1 (de) | 2008-04-10 |
| AU2003294830A1 (en) | 2004-07-14 |
| PL377661A1 (pl) | 2006-02-06 |
| DE60319430T2 (de) | 2009-02-26 |
| RU2005122901A (ru) | 2006-02-27 |
| MXPA05006437A (es) | 2005-08-19 |
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