ZA200609450B - Compounds and compositions as protein kinase inhibitors - Google Patents
Compounds and compositions as protein kinase inhibitors Download PDFInfo
- Publication number
- ZA200609450B ZA200609450B ZA200609450A ZA200609450A ZA200609450B ZA 200609450 B ZA200609450 B ZA 200609450B ZA 200609450 A ZA200609450 A ZA 200609450A ZA 200609450 A ZA200609450 A ZA 200609450A ZA 200609450 B ZA200609450 B ZA 200609450B
- Authority
- ZA
- South Africa
- Prior art keywords
- methyl
- ylamino
- imidazol
- pyrimidin
- phenyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 39
- 239000000203 mixture Substances 0.000 title description 8
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 2
- 239000003909 protein kinase inhibitor Substances 0.000 title description 2
- -1 cyano, hydroxy Chemical group 0.000 claims description 131
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 230000000694 effects Effects 0.000 claims description 22
- 108091000080 Phosphotransferase Proteins 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 21
- 102000020233 phosphotransferase Human genes 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 17
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims description 12
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 108091008606 PDGF receptors Proteins 0.000 claims description 12
- 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 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
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- 101100127166 Escherichia coli (strain K12) kefB gene Proteins 0.000 claims description 9
- 101100481410 Mus musculus Tek gene Proteins 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 claims description 7
- 101001115395 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 4 Proteins 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 230000007170 pathology Effects 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 102100023401 Dual specificity mitogen-activated protein kinase kinase 6 Human genes 0.000 claims description 4
- 101000624426 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 6 Proteins 0.000 claims description 4
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- 125000004076 pyridyl group Chemical group 0.000 claims description 4
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- 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 claims description 3
- 108700012928 MAPK14 Proteins 0.000 claims description 3
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- 102000054819 Mitogen-activated protein kinase 14 Human genes 0.000 claims description 3
- 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
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- UDVSXFLAQLXZMI-UHFFFAOYSA-N 1-[3-[[6-[2-(2-chloroanilino)imidazol-1-yl]pyrimidin-4-yl]amino]phenyl]ethanol Chemical compound CC(O)C1=CC=CC(NC=2N=CN=C(C=2)N2C(=NC=C2)NC=2C(=CC=CC=2)Cl)=C1 UDVSXFLAQLXZMI-UHFFFAOYSA-N 0.000 claims description 2
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- IJXYLILRNVOJNF-UHFFFAOYSA-N 2-benzyl-5-tert-butylpyrazole-3-carboxylic acid Chemical compound N1=C(C(C)(C)C)C=C(C(O)=O)N1CC1=CC=CC=C1 IJXYLILRNVOJNF-UHFFFAOYSA-N 0.000 claims description 2
- SMFQHYQIMXHCLV-UHFFFAOYSA-N 3-[[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]amino]-4-methyl-n-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC=C(S(=O)(=O)NC=2C=C(C=CC=2)C(F)(F)F)C=C1NC1=NC=CN1C(N=CN=1)=CC=1NC1CC1 SMFQHYQIMXHCLV-UHFFFAOYSA-N 0.000 claims description 2
- RBYJWCRKFLGNDB-UHFFFAOYSA-N 5-methylpyrazine-2-carboxylic acid Chemical compound CC1=CN=C(C(O)=O)C=N1 RBYJWCRKFLGNDB-UHFFFAOYSA-N 0.000 claims description 2
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- 150000004677 hydrates Chemical class 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
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- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 2
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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 2
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
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- BWHKNFIYRZHLTB-UHFFFAOYSA-N n-[3-[[1-[6-[(6-methoxypyridin-3-yl)amino]pyrimidin-4-yl]imidazol-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1NC1=CC(N2C(=NC=C2)NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=NC=N1 BWHKNFIYRZHLTB-UHFFFAOYSA-N 0.000 claims description 2
- OBHKRGWBSZURGD-UHFFFAOYSA-N n-[3-[[6-[2-(2-chloroanilino)imidazol-1-yl]pyrimidin-4-yl]amino]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(NC=2N=CN=C(C=2)N2C(=NC=C2)NC=2C(=CC=CC=2)Cl)=C1 OBHKRGWBSZURGD-UHFFFAOYSA-N 0.000 claims description 2
- IBWKFBOTIRPILV-UHFFFAOYSA-N n-[4-methyl-3-[[1-[2-(methylamino)pyrimidin-4-yl]imidazol-2-yl]amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound CNC1=NC=CC(N2C(=NC=C2)NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=N1 IBWKFBOTIRPILV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
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- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 claims description 2
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
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- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 2
- LBYJHYXGUVCRIY-UHFFFAOYSA-N 3-(4-methylimidazol-1-yl)-n-[4-methyl-3-[[1-[6-(methylamino)pyrimidin-4-yl]imidazol-2-yl]amino]phenyl]-5-(trifluoromethyl)benzamide Chemical compound C1=NC(NC)=CC(N2C(=NC=C2)NC=2C(=CC=C(NC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=2)C)=N1 LBYJHYXGUVCRIY-UHFFFAOYSA-N 0.000 claims 1
- KHGPMZRPUDCRMU-UHFFFAOYSA-N 3-n-[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]-4-methylbenzene-1,3-diamine Chemical compound CC1=CC=C(N)C=C1NC1=NC=CN1C1=CC(NC2CC2)=NC=N1 KHGPMZRPUDCRMU-UHFFFAOYSA-N 0.000 claims 1
- VNPVKZQHCXAIFQ-UHFFFAOYSA-N 4-[(4-ethylpiperazin-1-yl)methyl]-n-[4-methyl-3-[[1-[6-(pyridin-2-ylamino)pyrimidin-4-yl]imidazol-2-yl]amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1CN(CC)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N(C=CN=3)C=3N=CN=C(NC=4N=CC=CC=4)C=3)C(C)=CC=2)C=C1C(F)(F)F VNPVKZQHCXAIFQ-UHFFFAOYSA-N 0.000 claims 1
- PAFUGWLPSIKDNB-UHFFFAOYSA-N 4-chloro-n-[4-methyl-3-[[1-[6-(pyridin-2-ylamino)pyrimidin-4-yl]imidazol-2-yl]amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C=CN=2)C=2N=CN=C(NC=3N=CC=CC=3)C=2)C(C)=CC=C1NC(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 PAFUGWLPSIKDNB-UHFFFAOYSA-N 0.000 claims 1
- GFBPVYVWAHGFJY-UHFFFAOYSA-N 4-methyl-3-[[1-[6-[(4-methylpiperazin-1-yl)amino]pyrimidin-4-yl]imidazol-2-yl]amino]-n-[3-(trifluoromethyl)phenyl]benzamide Chemical compound C1CN(C)CCN1NC1=CC(N2C(=NC=C2)NC=2C(=CC=C(C=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)C)=NC=N1 GFBPVYVWAHGFJY-UHFFFAOYSA-N 0.000 claims 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- MUHKFQBTMMESMA-UHFFFAOYSA-N 5-tert-butyl-2-methyl-4-(morpholin-4-ylmethyl)furan-3-carboxylic acid Chemical compound OC(=O)C1=C(C)OC(C(C)(C)C)=C1CN1CCOCC1 MUHKFQBTMMESMA-UHFFFAOYSA-N 0.000 claims 1
- OJTHFYIZWALMRS-UHFFFAOYSA-N 5-tert-butyl-2-methyl-n-[4-methyl-3-[[1-[6-(2-morpholin-4-ylethylamino)pyrimidin-4-yl]imidazol-2-yl]amino]phenyl]pyrazole-3-carboxamide Chemical compound C1=C(NC=2N(C=CN=2)C=2N=CN=C(NCCN3CCOCC3)C=2)C(C)=CC=C1NC(=O)C1=CC(C(C)(C)C)=NN1C OJTHFYIZWALMRS-UHFFFAOYSA-N 0.000 claims 1
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- QTLMCFQRKYFGHO-UHFFFAOYSA-N 5-tert-butyl-n-[3-[[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]amino]-4-methylphenyl]-2-(diethylamino)furan-3-carboxamide Chemical compound O1C(C(C)(C)C)=CC(C(=O)NC=2C=C(NC=3N(C=CN=3)C=3N=CN=C(NC4CC4)C=3)C(C)=CC=2)=C1N(CC)CC QTLMCFQRKYFGHO-UHFFFAOYSA-N 0.000 claims 1
- MZZPWKOWUHKRQA-UHFFFAOYSA-N 5-tert-butyl-n-[3-[[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]amino]-4-methylphenyl]-2-methylfuran-3-carboxamide Chemical compound O1C(C(C)(C)C)=CC(C(=O)NC=2C=C(NC=3N(C=CN=3)C=3N=CN=C(NC4CC4)C=3)C(C)=CC=2)=C1C MZZPWKOWUHKRQA-UHFFFAOYSA-N 0.000 claims 1
- GQVGGAYHUCBGCY-UHFFFAOYSA-N 5-tert-butyl-n-[3-[[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]amino]-4-methylphenyl]thiophene-2-carboxamide Chemical compound C1=C(NC=2N(C=CN=2)C=2N=CN=C(NC3CC3)C=2)C(C)=CC=C1NC(=O)C1=CC=C(C(C)(C)C)S1 GQVGGAYHUCBGCY-UHFFFAOYSA-N 0.000 claims 1
- VUFXVQUAFMFQOB-UHFFFAOYSA-N 6-[2-(2-chloroanilino)imidazol-1-yl]-n-(6-methylpyridin-3-yl)pyrimidin-4-amine Chemical compound C1=NC(C)=CC=C1NC1=CC(N2C(=NC=C2)NC=2C(=CC=CC=2)Cl)=NC=N1 VUFXVQUAFMFQOB-UHFFFAOYSA-N 0.000 claims 1
- OPSILNJMXLHQBF-UHFFFAOYSA-N 6-[[6-[2-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]anilino]imidazol-1-yl]pyrimidin-4-yl]amino]pyridine-3-carboxamide Chemical compound C1=C(NC=2N(C=CN=2)C=2N=CN=C(NC=3N=CC(=CC=3)C(N)=O)C=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 OPSILNJMXLHQBF-UHFFFAOYSA-N 0.000 claims 1
- CUUKTKDADNIDCZ-UHFFFAOYSA-N CC(C)(C)[S+]1C(C([O-])=O)=CC=C1 Chemical compound CC(C)(C)[S+]1C(C([O-])=O)=CC=C1 CUUKTKDADNIDCZ-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- OCGVBVCQHSVQCU-UHFFFAOYSA-N n-(4-tert-butyl-1,3-thiazol-2-yl)-4-methyl-3-[[1-[6-[(4-methylpiperazin-1-yl)amino]pyrimidin-4-yl]imidazol-2-yl]amino]benzamide Chemical compound C1CN(C)CCN1NC1=CC(N2C(=NC=C2)NC=2C(=CC=C(C=2)C(=O)NC=2SC=C(N=2)C(C)(C)C)C)=NC=N1 OCGVBVCQHSVQCU-UHFFFAOYSA-N 0.000 claims 1
- ISAYYIGZKHCWGU-UHFFFAOYSA-N n-(5-tert-butyl-2-methylpyrazol-3-yl)-4-methyl-3-[[1-[6-(2-morpholin-4-ylethylamino)pyrimidin-4-yl]imidazol-2-yl]amino]benzamide Chemical compound CC1=CC=C(C(=O)NC=2N(N=C(C=2)C(C)(C)C)C)C=C1NC1=NC=CN1C(N=CN=1)=CC=1NCCN1CCOCC1 ISAYYIGZKHCWGU-UHFFFAOYSA-N 0.000 claims 1
- LHPVMKBNMAYDAJ-UHFFFAOYSA-N n-[3-[[1-(6-aminopyrimidin-4-yl)imidazol-2-yl]amino]-4-methylphenyl]-3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCN1C1=CC(C(=O)NC=2C=C(NC=3N(C=CN=3)C=3N=CN=C(N)C=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 LHPVMKBNMAYDAJ-UHFFFAOYSA-N 0.000 claims 1
- XMTWLEXAHAGZAI-UHFFFAOYSA-N n-[3-[[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]amino]-4-fluorophenyl]-3-(dimethylamino)-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(N(C)C)=CC(C(=O)NC=2C=C(NC=3N(C=CN=3)C=3N=CN=C(NC4CC4)C=3)C(F)=CC=2)=C1 XMTWLEXAHAGZAI-UHFFFAOYSA-N 0.000 claims 1
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- LPMYCGMNFRFXCF-UHFFFAOYSA-N n-[3-[[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]amino]-4-methylphenyl]-3-(4-ethylpiperazin-1-yl)-5-(trifluoromethyl)benzamide Chemical compound C1CN(CC)CCN1C1=CC(C(=O)NC=2C=C(NC=3N(C=CN=3)C=3N=CN=C(NC4CC4)C=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 LPMYCGMNFRFXCF-UHFFFAOYSA-N 0.000 claims 1
- PNMQPVWHPKIXOL-UHFFFAOYSA-N n-[3-[[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]amino]-4-methylphenyl]-3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC=3N(C=CN=3)C=3N=CN=C(NC4CC4)C=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 PNMQPVWHPKIXOL-UHFFFAOYSA-N 0.000 claims 1
- VUPUOHMYZZQALV-UHFFFAOYSA-N n-[3-[[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]amino]-4-methylphenyl]-3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCN1C1=CC(C(=O)NC=2C=C(NC=3N(C=CN=3)C=3N=CN=C(NC4CC4)C=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 VUPUOHMYZZQALV-UHFFFAOYSA-N 0.000 claims 1
- VTSNQZVBFOIVFR-UHFFFAOYSA-N n-[3-[[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]amino]-4-methylphenyl]furan-2-carboxamide Chemical compound C1=C(NC=2N(C=CN=2)C=2N=CN=C(NC3CC3)C=2)C(C)=CC=C1NC(=O)C1=CC=CO1 VTSNQZVBFOIVFR-UHFFFAOYSA-N 0.000 claims 1
- XIYQJSVDPFECRJ-UHFFFAOYSA-N n-[3-[[1-[6-(cyclopropylamino)pyrimidin-4-yl]imidazol-2-yl]amino]-4-methylphenyl]pyridazine-4-carboxamide Chemical compound C1=C(NC=2N(C=CN=2)C=2N=CN=C(NC3CC3)C=2)C(C)=CC=C1NC(=O)C1=CC=NN=C1 XIYQJSVDPFECRJ-UHFFFAOYSA-N 0.000 claims 1
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Families Citing this family (116)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR045047A1 (es) * | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| TW200533357A (en) * | 2004-01-08 | 2005-10-16 | Millennium Pharm Inc | 2-(amino-substituted)-4-aryl pyrimidines and related compounds useful for treating inflammatory diseases |
| WO2006064375A2 (en) * | 2004-12-16 | 2006-06-22 | Ab Science | Aminoaryl substituted five-membered ring heterocyclic compounds for the treatment of diseases |
| CN101218229A (zh) * | 2005-05-05 | 2008-07-09 | 阿斯利康(瑞典)有限公司 | 吡唑基-氨基取代的嘧啶及其在癌症治疗中的应用 |
| WO2006122150A1 (en) | 2005-05-10 | 2006-11-16 | Incyte Corporation | Modulators of indoleamine 2,3-dioxygenase and methods of using the same |
| UA116187C2 (uk) | 2005-12-13 | 2018-02-26 | Інсайт Холдінгс Корпорейшн | ГЕТЕРОАРИЛЗАМІЩЕНІ ПІРОЛО[2,3-b]ПІРИДИНИ Й ПІРОЛО[2,3-b]ПІРИМІДИНИ ЯК ІНГІБІТОРИ ЯНУС-КІНАЗИ |
| MX2008012971A (es) | 2006-04-07 | 2008-10-15 | Novartis Ag | Combinacion que comprende a) un compuesto de pirimidil-amino-benza mida, y b) un inhibidor de cinasa thr315lle. |
| MX2009002229A (es) | 2006-09-08 | 2009-03-16 | Hoffmann La Roche | Benzotriazoles como moduladores de cinasas. |
| KR20090065512A (ko) | 2006-09-22 | 2009-06-22 | 노파르티스 아게 | Ａｂｌ 티로신 키나제 억제제에 의해 필라델피아-양성 백혈병의 치료를 최적화시키는 방법 |
| CN103739595A (zh) | 2006-10-02 | 2014-04-23 | Irm责任有限公司 | 作为蛋白激酶抑制剂的化合物和组合物 |
| JP2010512405A (ja) * | 2006-12-11 | 2010-04-22 | アイアールエム・リミテッド・ライアビリティ・カンパニー | キナーゼ阻害剤としての化合物および組成物 |
| ES2714092T3 (es) | 2007-06-13 | 2019-05-27 | Incyte Holdings Corp | Uso de sales del inhibidor de quinasas Janus (R)-3-(4-(7H-pirrolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il)-3-ciclopentilpropanonitrilo |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| EP2300013B1 (en) | 2008-05-21 | 2017-09-06 | Ariad Pharmaceuticals, Inc. | Phosphorous derivatives as kinase inhibitors |
| WO2009158432A2 (en) | 2008-06-27 | 2009-12-30 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| LT2824100T (lt) | 2008-07-08 | 2018-05-10 | Incyte Holdings Corporation | 1,2,5-oksadiazolai, kaip indolamino 2,3-dioksigenazės inhibitoriai |
| WO2010100127A1 (en) * | 2009-03-04 | 2010-09-10 | Novartis Ag | Disubstituted imidazole derivatives as modulators of raf kinase |
| UA106078C2 (uk) | 2009-05-22 | 2014-07-25 | Інсайт Корпорейшн | 3-[4-(7H-ПІРОЛО[2,3-d]ПІРИМІДИН-4-ІЛ)-1H-ПІРАЗОЛ-1-ІЛ]ОКТАН- АБО ГЕПТАННІТРИЛ ЯК JAK-ІНГІБІТОРИ |
| TW201100429A (en) | 2009-05-22 | 2011-01-01 | Incyte Corp | N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
| WO2010144909A1 (en) | 2009-06-12 | 2010-12-16 | Novartis Ag | Fused heterocyclic compounds and their uses |
| JO3002B1 (ar) | 2009-08-28 | 2016-09-05 | Irm Llc | مركبات و تركيبات كمثبطات كيناز بروتين |
| WO2011028685A1 (en) | 2009-09-01 | 2011-03-10 | Incyte Corporation | Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
| AU2010343102B2 (en) | 2009-12-29 | 2016-03-24 | Dana-Farber Cancer Institute, Inc. | Type II Raf kinase inhibitors |
| WO2011103423A1 (en) | 2010-02-18 | 2011-08-25 | Incyte Corporation | Cyclobutane and methylcyclobutane derivatives as janus kinase inhibitors |
| TWI643857B (zh) | 2010-03-10 | 2018-12-11 | 英塞特公司 | 作為ｊａｋ１抑制劑之哌啶-４-基三亞甲亞胺衍生物 |
| PE20130216A1 (es) | 2010-05-21 | 2013-02-27 | Incyte Corp | Formulacion topica para un inhibidor de jak |
| JP2012102090A (ja) * | 2010-10-15 | 2012-05-31 | Sumitomo Chemical Co Ltd | ピリミジン化合物およびその有害生物防除用途 |
| WO2012068440A1 (en) | 2010-11-19 | 2012-05-24 | Incyte Corporation | Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors |
| JP5917545B2 (ja) | 2010-11-19 | 2016-05-18 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｊａｋ阻害剤としてのシクロブチル置換ピロロピリジンおよびピロロピリミジン誘導体 |
| JP5999177B2 (ja) | 2011-05-04 | 2016-09-28 | アリアド・ファーマシューティカルズ・インコーポレイテッド | Ｅｇｆｒ発動性がんの細胞増殖阻害用化合物 |
| RU2477723C2 (ru) | 2011-06-16 | 2013-03-20 | Общество С Ограниченной Ответственностью "Фьюжн Фарма" | Ингибиторы протеинкиназ (варианты), их применение для лечения онкологических заболеваний и фармацевтическая композиция на их основе |
| AR086983A1 (es) | 2011-06-20 | 2014-02-05 | Incyte Corp | Derivados de azetidinil fenil, piridil o pirazinil carboxamida como inhibidores de jak |
| TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物 |
| UA111854C2 (uk) | 2011-09-07 | 2016-06-24 | Інсайт Холдінгс Корпорейшн | Способи і проміжні сполуки для отримання інгібіторів jak |
| CA2855243C (en) | 2011-11-11 | 2020-04-14 | Novartis Ag | Method of treating a proliferative disease |
| AU2012340200B2 (en) | 2011-11-17 | 2017-10-12 | Dana-Farber Cancer Institute, Inc. | Inhibitors of c-Jun-N-Terminal Kinase (JNK) |
| PL2782557T3 (pl) | 2011-11-23 | 2019-03-29 | Array Biopharma, Inc. | Formulacje farmaceutyczne |
| GB201204384D0 (en) | 2012-03-13 | 2012-04-25 | Univ Dundee | Anti-flammatory agents |
| US20150166591A1 (en) | 2012-05-05 | 2015-06-18 | Ariad Pharmaceuticals, Inc. | Methods and compositions for raf kinase mediated diseases |
| US9193733B2 (en) | 2012-05-18 | 2015-11-24 | Incyte Holdings Corporation | Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors |
| ES2704744T3 (es) | 2012-06-13 | 2019-03-19 | Incyte Holdings Corp | Compuestos tricíclicos sustituidos como inhibidores de FGFR |
| AU2013320972B2 (en) * | 2012-09-27 | 2018-08-30 | Chugai Seiyaku Kabushiki Kaisha | FGFR3 fusion gene and pharmaceutical drug targeting same |
| US10112927B2 (en) | 2012-10-18 | 2018-10-30 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
| WO2014063061A1 (en) | 2012-10-19 | 2014-04-24 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged small molecules as inducers of protein degradation |
| US10000483B2 (en) | 2012-10-19 | 2018-06-19 | Dana-Farber Cancer Institute, Inc. | Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof |
| CN104918945B (zh) | 2012-11-01 | 2018-01-05 | 因赛特公司 | 作为jak抑制剂的三环稠合噻吩衍生物 |
| NZ748448A (en) | 2012-11-15 | 2019-12-20 | Incyte Holdings Corp | Sustained-release dosage forms of ruxolitinib |
| TWI687220B (zh) | 2013-03-01 | 2020-03-11 | 美商英塞特控股公司 | 吡唑并嘧啶衍生物治療PI3Kδ相關病症之用途 |
| TWI634121B (zh) | 2013-03-06 | 2018-09-01 | 英塞特控股公司 | 用於製備ｊａｋ抑制劑之方法及中間物 |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| CN109776525B (zh) | 2013-04-19 | 2022-01-21 | 因赛特控股公司 | 作为fgfr抑制剂的双环杂环 |
| KR20220103810A (ko) | 2013-08-07 | 2022-07-22 | 인사이트 코포레이션 | Jak1 억제제용 지속 방출 복용 형태 |
| CA2927917C (en) | 2013-10-18 | 2022-08-09 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of proliferative diseases |
| US10047070B2 (en) | 2013-10-18 | 2018-08-14 | Dana-Farber Cancer Institute, Inc. | Polycyclic inhibitors of cyclin-dependent kinase 7 (CDK7) |
| WO2015164614A1 (en) | 2014-04-23 | 2015-10-29 | Dana-Farber Cancer Institute, Inc. | Janus kinase inhibitors and uses thereof |
| WO2015164604A1 (en) | 2014-04-23 | 2015-10-29 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged janus kinase inhibitors and uses thereof |
| CR20160553A (es) | 2014-04-30 | 2017-04-25 | Incyte Corp | Procesos para preparar un inhibidor de jak1 y nuevas formas de este |
| WO2015184305A1 (en) | 2014-05-30 | 2015-12-03 | Incyte Corporation | TREATMENT OF CHRONIC NEUTROPHILIC LEUKEMIA (CNL) AND ATYPICAL CHRONIC MYELOID LEUKEMIA (aCML) BY INHIBITORS OF JAK1 |
| EP3171874B1 (en) * | 2014-07-21 | 2020-11-18 | Dana-Farber Cancer Institute, Inc. | Imidazolyl kinase inhibitors and uses thereof |
| DK3172213T3 (da) | 2014-07-21 | 2021-12-13 | Dana Farber Cancer Inst Inc | Makrocykliske kinasehæmmere og anvendelser deraf |
| AU2015300782B2 (en) | 2014-08-08 | 2020-04-16 | Dana-Farber Cancer Institute, Inc. | Uses of salt-inducible kinase (SIK) inhibitors |
| JP6854762B2 (ja) | 2014-12-23 | 2021-04-07 | ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド | サイクリン依存性キナーゼ７（ｃｄｋ７）の阻害剤 |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| AU2016219822B2 (en) | 2015-02-20 | 2020-07-09 | Incyte Holdings Corporation | Bicyclic heterocycles as FGFR inhibitors |
| EP3273966B1 (en) | 2015-03-27 | 2023-05-03 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
| EP3307728A4 (en) | 2015-06-12 | 2019-07-17 | Dana Farber Cancer Institute, Inc. | ASSOCIATION THERAPY USING TRANSCRIPTION INHIBITORS AND KINASE INHIBITORS |
| JP7028766B2 (ja) | 2015-09-09 | 2022-03-02 | ダナ－ファーバー キャンサー インスティテュート， インコーポレイテッド | サイクリン依存性キナーゼの阻害剤 |
| JP6626981B2 (ja) * | 2016-01-29 | 2019-12-25 | サムジン ファーマシューティカル カンパニー，リミテッド | Ｊｎｋ阻害活性を有する新規なイミダゾール誘導体およびその用途 |
| MX2018010374A (es) | 2016-03-01 | 2019-03-28 | Propellon Therapeutics Inc | Inhibidores del enlace proteína-proteína de wdr5. |
| EP3423437A4 (en) | 2016-03-01 | 2019-07-24 | Propellon Therapeutics Inc. | INHIBITORS OF THE LINK BETWEEN THE WDR5 PROTEIN AND ITS LIAISON PARTNERS |
| AU2017291812B2 (en) | 2016-07-05 | 2023-12-14 | Dana-Farber Cancer Institute, Inc. | Bicyclic urea kinase inhibitors and uses thereof |
| US11241435B2 (en) | 2016-09-16 | 2022-02-08 | The General Hospital Corporation | Uses of salt-inducible kinase (SIK) inhibitors for treating osteoporosis |
| BR112019017741A2 (pt) | 2017-02-28 | 2020-04-07 | Dana Farber Cancer Inst Inc | usos de pirimidopirimidinonas como inibidores de sik |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| PT3697789T (pt) | 2017-10-18 | 2021-12-31 | Incyte Corp | Derivados de imidazol condensados substituídos por grupos hidróxi terciários como inibidores de pi3kgama |
| AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
| US11306079B2 (en) | 2017-12-21 | 2022-04-19 | Incyte Corporation | 3-(5-amino-pyrazin-2-yl)-benzenesulfonamide derivatives and related compounds as PI3K-gamma kinase inhibitors |
| AU2019213665B2 (en) | 2018-01-30 | 2024-06-13 | Incyte Corporation | Processes for preparing (1 -(3-fluoro-2-(trifluoromethyl)isonicotinyl)piperidine-4-one) |
| HRP20220331T1 (hr) | 2018-03-08 | 2022-05-13 | Incyte Corporation | Spojevi aminopirazin diola kao inhibitori pi3k-y |
| SI3773593T1 (sl) | 2018-03-30 | 2024-08-30 | Incyte Corporation | Zdravljenje hidradenitisa suppurative z zaviralci jak |
| US11220510B2 (en) | 2018-04-09 | 2022-01-11 | Incyte Corporation | Pyrrole tricyclic compounds as A2A / A2B inhibitors |
| BR112020022392A2 (pt) | 2018-05-04 | 2021-02-02 | Incyte Corporation | formas sólidas de um inibidor de fgfr e processos para preparação das mesmas |
| MX2020011639A (es) | 2018-05-04 | 2021-02-15 | Incyte Corp | Sales de un inhibidor de receptores de factor de crecimiento de fibroblastos (fgfr). |
| JP7391046B2 (ja) | 2018-05-18 | 2023-12-04 | インサイト・コーポレイション | Ａ２ａ／ａ２ｂ阻害剤としての縮合ピリミジン誘導体 |
| US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
| EP3818063A1 (en) | 2018-07-05 | 2021-05-12 | Incyte Corporation | Fused pyrazine derivatives as a2a / a2b inhibitors |
| HRP20240252T1 (hr) | 2018-09-05 | 2024-05-24 | Incyte Corporation | Kristalni oblici inhibitora fosfoinozitid 3 kinaze (pi3k) |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| US11161838B2 (en) | 2018-11-13 | 2021-11-02 | Incyte Corporation | Heterocyclic derivatives as PI3K inhibitors |
| US11078204B2 (en) | 2018-11-13 | 2021-08-03 | Incyte Corporation | Heterocyclic derivatives as PI3K inhibitors |
| WO2020102216A1 (en) | 2018-11-13 | 2020-05-22 | Incyte Corporation | Substituted heterocyclic derivatives as pi3k inhibitors |
| US11596692B1 (en) | 2018-11-21 | 2023-03-07 | Incyte Corporation | PD-L1/STING conjugates and methods of use |
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| US11472791B2 (en) | 2019-03-05 | 2022-10-18 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as CDK2 inhibitors |
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| WO2021113479A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
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| US12084453B2 (en) | 2021-12-10 | 2024-09-10 | Incyte Corporation | Bicyclic amines as CDK12 inhibitors |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| US20230399331A1 (en) | 2022-06-14 | 2023-12-14 | Incyte Corporation | Solid forms of jak inhibitor and process of preparing the same |
| WO2024015731A1 (en) | 2022-07-11 | 2024-01-18 | Incyte Corporation | Fused tricyclic compounds as inhibitors of kras g12v mutants |
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| US6432947B1 (en) * | 1997-02-19 | 2002-08-13 | Berlex Laboratories, Inc. | N-heterocyclic derivatives as NOS inhibitors |
| JP2002302445A (ja) * | 2001-02-02 | 2002-10-18 | Takeda Chem Ind Ltd | Ｊｎｋ阻害剤 |
| MXPA03009257A (es) * | 2001-04-10 | 2004-01-29 | Vertex Pharma | Derivados de isoxaxol como inhibidores de src y otras proteinas cinasas. |
| WO2002083667A2 (en) * | 2001-04-13 | 2002-10-24 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
| US6884804B2 (en) * | 2001-05-16 | 2005-04-26 | Vertex Pharmaceuticals Incorporated | Inhibitors of Src and other protein kinases |
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- 2005-06-09 AU AU2005254982A patent/AU2005254982B2/en not_active Ceased
- 2005-06-09 TW TW094119144A patent/TW200610762A/zh unknown
- 2005-06-09 MX MXPA06014247A patent/MXPA06014247A/es active IP Right Grant
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| US20070225286A1 (en) | 2007-09-27 |
| EP1758892A1 (en) | 2007-03-07 |
| MXPA06014247A (es) | 2007-03-12 |
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| AU2005254982B2 (en) | 2008-11-27 |
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| CA2567662A1 (en) | 2005-12-29 |
| JP2008502729A (ja) | 2008-01-31 |
| TNSN06406A1 (en) | 2008-02-22 |
| AU2005254982A1 (en) | 2005-12-29 |
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| EP1758892B1 (en) | 2012-10-17 |
| ECSP067070A (es) | 2007-01-26 |
| CN1960988A (zh) | 2007-05-09 |
| AR049511A1 (es) | 2006-08-09 |
| IL179613A0 (en) | 2007-05-15 |
| TW200610762A (en) | 2006-04-01 |
| MA28679B1 (fr) | 2007-06-01 |
| WO2005123719A1 (en) | 2005-12-29 |
| RU2401265C2 (ru) | 2010-10-10 |
| EP1758892A4 (en) | 2010-07-28 |
| ES2396135T3 (es) | 2013-02-19 |
| BRPI0511978A (pt) | 2008-01-22 |
| CA2567662C (en) | 2012-11-27 |
| MY144044A (en) | 2011-07-29 |
| JP4688876B2 (ja) | 2011-05-25 |
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