KR20090029832A - 단백질 키나제 억제제로서의 [4,5']비피리미디닐-6,4'-디아민 유도체 - Google Patents

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Publication number

KR20090029832A

KR20090029832A KR1020097002815A KR20097002815A KR20090029832A KR 20090029832 A KR20090029832 A KR 20090029832A KR 1020097002815 A KR1020097002815 A KR 1020097002815A KR 20097002815 A KR20097002815 A KR 20097002815A KR 20090029832 A KR20090029832 A KR 20090029832A

Authority

KR

South Korea

Prior art keywords

pyridin

bipyrimidinyl

dimethoxy

phenyl

methyl

Prior art date

2006-07-12

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.)

Withdrawn

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• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title 1
• 239000003909 protein kinase inhibitor Substances 0.000 title 1
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• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 53
• 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 47
• 102000020233 phosphotransferase Human genes 0.000 claims abstract description 47
• 238000000034 method Methods 0.000 claims abstract description 43
• 201000010099 disease Diseases 0.000 claims abstract description 39
• 230000000694 effects Effects 0.000 claims abstract description 38
• 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims abstract description 35
• 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims abstract description 35
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• -1 piperazino Chemical group 0.000 claims description 171
• 229910052739 hydrogen Inorganic materials 0.000 claims description 64
• 239000001257 hydrogen Substances 0.000 claims description 63
• 125000000217 alkyl group Chemical group 0.000 claims description 57
• 239000000203 mixture Substances 0.000 claims description 48
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
• 150000003839 salts Chemical class 0.000 claims description 35
• 125000002950 monocyclic group Chemical group 0.000 claims description 34
• 229920006395 saturated elastomer Polymers 0.000 claims description 30
• 229910052799 carbon Inorganic materials 0.000 claims description 29
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 26
• 229910052717 sulfur Inorganic materials 0.000 claims description 24
• 229910052760 oxygen Inorganic materials 0.000 claims description 23
• 230000005764 inhibitory process Effects 0.000 claims description 18
• 125000002947 alkylene group Chemical group 0.000 claims description 15
• 125000002619 bicyclic group Chemical group 0.000 claims description 15
• 150000001204 N-oxides Chemical class 0.000 claims description 14
• 125000003545 alkoxy group Chemical group 0.000 claims description 14
• 150000002431 hydrogen Chemical class 0.000 claims description 14
• 125000003118 aryl group Chemical group 0.000 claims description 11
• 125000005843 halogen group Chemical group 0.000 claims description 11
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 10
• 239000012453 solvate Substances 0.000 claims description 10
• 241001465754 Metazoa Species 0.000 claims description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
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• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 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 6
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 6
• 230000007170 pathology Effects 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
• 125000001424 substituent group Chemical group 0.000 claims description 5
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• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
• 125000001246 bromo group Chemical group Br* 0.000 claims description 4
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
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• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
• 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
• TYOCSGNRWAHCPK-UHFFFAOYSA-N 1-[3-[[6-[4-(2,6-dichloro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]phenyl]ethanol Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3C=C(C=CC=3)C(C)O)C=2)=C1Cl TYOCSGNRWAHCPK-UHFFFAOYSA-N 0.000 claims description 2
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• AYJYBVQKLXRDQJ-UHFFFAOYSA-N 1-[4-[[6-[[6-[4-(2-chloro-6-fluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]methyl]piperazin-1-yl]-2-hydroxyethanone Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(CC4)C(=O)CO)=CC=3)C=2)=C1F AYJYBVQKLXRDQJ-UHFFFAOYSA-N 0.000 claims description 2
• FFHPXSVUVZJSNL-UHFFFAOYSA-N 1-[6-[[6-[3-(2,6-dichloro-3,5-dimethoxyanilino)pyrazin-2-yl]pyrimidin-4-yl]amino]pyridin-3-yl]ethanol Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=NC=CN=2)C=2N=CN=C(NC=3N=CC(=CC=3)C(C)O)C=2)=C1Cl FFHPXSVUVZJSNL-UHFFFAOYSA-N 0.000 claims description 2
• YWENEVBVNPLSKO-UHFFFAOYSA-N 1-[6-[[6-[4-(2,6-difluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]ethanol Chemical compound COC1=CC(OC)=C(F)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(=CC=3)C(C)O)C=2)=C1F YWENEVBVNPLSKO-UHFFFAOYSA-N 0.000 claims description 2
• STNPCJBTHDGVDG-UHFFFAOYSA-N 1-[6-[[6-[4-(2-chloro-3,5-dimethoxy-6-methylanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]ethanol Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(=CC=3)C(C)O)C=2)=C1C STNPCJBTHDGVDG-UHFFFAOYSA-N 0.000 claims description 2
• RMCRWRACPLILML-UHFFFAOYSA-N 2-[4-[6-[[6-[3-(2,6-dichloro-3,5-dimethoxyanilino)pyrazin-2-yl]pyrimidin-4-yl]amino]pyridin-3-yl]piperazin-1-yl]ethanol Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=NC=CN=2)C=2N=CN=C(NC=3N=CC(=CC=3)N3CCN(CCO)CC3)C=2)=C1Cl RMCRWRACPLILML-UHFFFAOYSA-N 0.000 claims description 2
• HBJDUPZNFBWSNF-UHFFFAOYSA-N 2-[4-[[6-[[6-[4-(2,6-difluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]methyl]piperazin-1-yl]ethanol Chemical compound COC1=CC(OC)=C(F)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(CCO)CC4)=CC=3)C=2)=C1F HBJDUPZNFBWSNF-UHFFFAOYSA-N 0.000 claims description 2
• SWQLRHRBOQUCSW-UHFFFAOYSA-N 2-[4-[[6-[[6-[4-(2-chloro-6-fluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]methyl]piperazin-1-yl]ethanol Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(CCO)CC4)=CC=3)C=2)=C1F SWQLRHRBOQUCSW-UHFFFAOYSA-N 0.000 claims description 2
• XYIBIKYKRKQRGW-UHFFFAOYSA-N 2-[4-[[6-[[6-[4-(2-fluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]methyl]piperazin-1-yl]ethanol Chemical compound COC1=CC(OC)=CC(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(CCO)CC4)=CC=3)C=2)=C1F XYIBIKYKRKQRGW-UHFFFAOYSA-N 0.000 claims description 2
• 125000000872 2-diethylaminoethoxy group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 2
• YUCPGZSYMDFVJE-UHFFFAOYSA-N 3-(6-aminopyrimidin-4-yl)-n-(2,6-dichlorophenyl)pyrazin-2-amine Chemical compound C1=NC(N)=CC(C=2C(=NC=CN=2)NC=2C(=CC=CC=2Cl)Cl)=N1 YUCPGZSYMDFVJE-UHFFFAOYSA-N 0.000 claims description 2
• FHVWPPCTAIQSHC-UHFFFAOYSA-N 3-(6-aminopyrimidin-4-yl)-n-(2,6-difluoro-3-methoxyphenyl)pyrazin-2-amine Chemical compound COC1=CC=C(F)C(NC=2C(=NC=CN=2)C=2N=CN=C(N)C=2)=C1F FHVWPPCTAIQSHC-UHFFFAOYSA-N 0.000 claims description 2
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• VHTOEAQTTZXCOA-UHFFFAOYSA-N 6-[4-(2-chloro-3,5-dimethoxy-6-methylanilino)pyrimidin-5-yl]-n-[5-(morpholin-4-ylmethyl)pyridin-2-yl]pyrimidin-4-amine Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCOCC4)=CC=3)C=2)=C1C VHTOEAQTTZXCOA-UHFFFAOYSA-N 0.000 claims description 2
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