CA2536535A1 - Compounds and compositions as protein kinase inhibitors - Google Patents
Compounds and compositions as protein kinase inhibitors Download PDFInfo
- Publication number
- CA2536535A1 CA2536535A1 CA002536535A CA2536535A CA2536535A1 CA 2536535 A1 CA2536535 A1 CA 2536535A1 CA 002536535 A CA002536535 A CA 002536535A CA 2536535 A CA2536535 A CA 2536535A CA 2536535 A1 CA2536535 A1 CA 2536535A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- phenyl
- amide
- pyrimidine
- pyrrolo
- 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.)
- Abandoned
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 115
- 239000000203 mixture Substances 0.000 title description 28
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 2
- 239000003909 protein kinase inhibitor Substances 0.000 title description 2
- 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 abstract description 37
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 25
- 201000010099 disease Diseases 0.000 claims abstract description 24
- 230000000694 effects Effects 0.000 claims abstract description 23
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims abstract description 17
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims abstract description 17
- 101100457333 Homo sapiens MAPK11 gene Proteins 0.000 claims abstract description 16
- 101150028321 Lck gene Proteins 0.000 claims abstract description 16
- 108700036166 Mitogen-Activated Protein Kinase 11 Proteins 0.000 claims abstract description 16
- 102100026929 Mitogen-activated protein kinase 11 Human genes 0.000 claims abstract description 16
- 101150046814 SAPK2 gene Proteins 0.000 claims abstract description 16
- 108010091528 Proto-Oncogene Proteins B-raf Proteins 0.000 claims abstract description 15
- 102000018471 Proto-Oncogene Proteins B-raf Human genes 0.000 claims abstract description 15
- 101150056950 Ntrk2 gene Proteins 0.000 claims abstract description 14
- 102100023401 Dual specificity mitogen-activated protein kinase kinase 6 Human genes 0.000 claims abstract description 13
- 101150036586 FES gene Proteins 0.000 claims abstract description 13
- 101000624426 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 6 Proteins 0.000 claims abstract description 13
- 101100272634 Mus musculus Bmx gene Proteins 0.000 claims abstract description 13
- 101000922131 Homo sapiens Tyrosine-protein kinase CSK Proteins 0.000 claims abstract description 11
- 101001045447 Synechocystis sp. (strain PCC 6803 / Kazusa) Sensor histidine kinase Hik2 Proteins 0.000 claims abstract description 11
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Chemical class 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 29
- -1 hydroxy C1-6alkyl Chemical group 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 230000005764 inhibitory process Effects 0.000 claims description 12
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- GUXRZPJLPDVPJS-UHFFFAOYSA-N 4-chloro-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(Cl)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 GUXRZPJLPDVPJS-UHFFFAOYSA-N 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 229910020008 S(O) Inorganic materials 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 5
- RLWJHNPBSIVWCW-UHFFFAOYSA-N 4-chloro-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(Cl)=C4C=C3)C(C)=CC=2)C=C1 RLWJHNPBSIVWCW-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 230000007170 pathology Effects 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 150000004677 hydrates Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- MQIPQQLXOZJHTP-UHFFFAOYSA-N n-[5-[[3-fluoro-5-(trifluoromethyl)benzoyl]amino]-2-methylphenyl]-4-[3-(1-hydroxyethyl)anilino]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=C(F)C=3)C(F)(F)F)C=2)C)=C1 MQIPQQLXOZJHTP-UHFFFAOYSA-N 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 2
- TZPPOOXFHQMTSD-UHFFFAOYSA-N 4-(3-acetamidoanilino)-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(=O)NC1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=C1 TZPPOOXFHQMTSD-UHFFFAOYSA-N 0.000 claims description 2
- ZSPBAHOTUQKQOK-UHFFFAOYSA-N 4-(3-bromoanilino)-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(Br)C=CC=5)=C4C=C3)C(C)=CC=2)C=C1 ZSPBAHOTUQKQOK-UHFFFAOYSA-N 0.000 claims description 2
- PWWKJTCSJICONG-UHFFFAOYSA-N 4-(3-bromoanilino)-n-[3-[(4-morpholin-4-ylphenyl)carbamoyl]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound BrC1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C=C(C=CC=2)C(=O)NC=2C=CC(=CC=2)N2CCOCC2)=C1 PWWKJTCSJICONG-UHFFFAOYSA-N 0.000 claims description 2
- ATNBRXYGVWYSSS-UHFFFAOYSA-N 4-(3-carbamoylanilino)-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)C(N)=O)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 ATNBRXYGVWYSSS-UHFFFAOYSA-N 0.000 claims description 2
- UADDISIFXJFVJE-UHFFFAOYSA-N 4-(3-carbamoylanilino)-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(NC=4C=C(C=CC=4)C(N)=O)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 UADDISIFXJFVJE-UHFFFAOYSA-N 0.000 claims description 2
- DIAUEZFTEANPKW-UHFFFAOYSA-N 4-(3-carbamoylanilino)-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)C(N)=O)=C4C=C3)C(C)=CC=2)C=C1 DIAUEZFTEANPKW-UHFFFAOYSA-N 0.000 claims description 2
- WBXFQDNGRMJSEU-UHFFFAOYSA-N 4-(3-chloroanilino)-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(Cl)C=CC=5)=C4C=C3)C(C)=CC=2)C=C1 WBXFQDNGRMJSEU-UHFFFAOYSA-N 0.000 claims description 2
- SSPBSSSLXNCQBJ-UHFFFAOYSA-N 4-(3-cyanoanilino)-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)C#N)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 SSPBSSSLXNCQBJ-UHFFFAOYSA-N 0.000 claims description 2
- SQFOGKADMIALOQ-UHFFFAOYSA-N 4-(3-fluoroanilino)-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(F)C=CC=5)=C4C=C3)C(C)=CC=2)C=C1 SQFOGKADMIALOQ-UHFFFAOYSA-N 0.000 claims description 2
- NMILQUSRDCKFFI-UHFFFAOYSA-N 4-(3-methylanilino)-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C)C=CC=5)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 NMILQUSRDCKFFI-UHFFFAOYSA-N 0.000 claims description 2
- ZQFYMEFSGXPSPT-UHFFFAOYSA-N 4-(4-carbamoylanilino)-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(NC=4C=CC(=CC=4)C(N)=O)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 ZQFYMEFSGXPSPT-UHFFFAOYSA-N 0.000 claims description 2
- DDSSBKNEYDTIMA-UHFFFAOYSA-N 4-(4-fluoro-2-methylanilino)-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C(=CC(F)=CC=5)C)=C4C=C3)C(C)=CC=2)C=C1 DDSSBKNEYDTIMA-UHFFFAOYSA-N 0.000 claims description 2
- VPNKGBSMPKBIAY-UHFFFAOYSA-N 4-[3-(1-hydroxyethyl)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)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)=C1 VPNKGBSMPKBIAY-UHFFFAOYSA-N 0.000 claims description 2
- FWZPOTDOHKDVIT-UHFFFAOYSA-N 4-[3-(1-hydroxyethyl)anilino]-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=C1 FWZPOTDOHKDVIT-UHFFFAOYSA-N 0.000 claims description 2
- WOQKHRKDYWZNEG-UHFFFAOYSA-N 4-[3-(2-hydroxypropan-2-yl)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)C(C)(C)O)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 WOQKHRKDYWZNEG-UHFFFAOYSA-N 0.000 claims description 2
- WPKFPABZEAONQB-UHFFFAOYSA-N 4-[3-(2-methoxyethylcarbamoyl)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound COCCNC(=O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)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)=C1 WPKFPABZEAONQB-UHFFFAOYSA-N 0.000 claims description 2
- PJTVXNSVTIVHAJ-UHFFFAOYSA-N 4-[3-(butylsulfamoyl)anilino]-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CCCCNS(=O)(=O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=CC(CN4CCN(C)CC4)=CC=3)C=2)C)=C1 PJTVXNSVTIVHAJ-UHFFFAOYSA-N 0.000 claims description 2
- VMEAGAJMGGCAEK-UHFFFAOYSA-N 4-[3-(dimethylamino)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CN(C)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)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)=C1 VMEAGAJMGGCAEK-UHFFFAOYSA-N 0.000 claims description 2
- CGFZWFDOGHQSOP-UHFFFAOYSA-N 4-[3-(dimethylamino)anilino]-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CN(C)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=C1 CGFZWFDOGHQSOP-UHFFFAOYSA-N 0.000 claims description 2
- XQIKPMJOJVFLIQ-UHFFFAOYSA-N 4-[3-(hydroxymethyl)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(CO)C=CC=5)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 XQIKPMJOJVFLIQ-UHFFFAOYSA-N 0.000 claims description 2
- AYLLCEFPZNBRLH-UHFFFAOYSA-N 4-[3-(hydroxymethyl)anilino]-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(NC=4C=C(CO)C=CC=4)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 AYLLCEFPZNBRLH-UHFFFAOYSA-N 0.000 claims description 2
- GHHAQSBCUFDLEA-UHFFFAOYSA-N 4-[3-(hydroxymethyl)anilino]-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(CO)C=CC=5)=C4C=C3)C(C)=CC=2)C=C1 GHHAQSBCUFDLEA-UHFFFAOYSA-N 0.000 claims description 2
- KWQOKBQJOVNBTN-UHFFFAOYSA-N 4-[3-(methylcarbamoyl)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CNC(=O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)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)=C1 KWQOKBQJOVNBTN-UHFFFAOYSA-N 0.000 claims description 2
- TWZJCYQRTFJSAF-UHFFFAOYSA-N 4-chloro-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(Cl)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 TWZJCYQRTFJSAF-UHFFFAOYSA-N 0.000 claims description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
- FTVDRSKMAKDXMF-UHFFFAOYSA-N [3-[[7-[[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]carbamoyl]pyrrolo[2,3-d]pyrimidin-4-yl]amino]phenyl]methyl acetate Chemical compound CC(=O)OCC1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)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)=C1 FTVDRSKMAKDXMF-UHFFFAOYSA-N 0.000 claims description 2
- KLMBMLLBCGFEKR-UHFFFAOYSA-N [3-[[7-[[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]carbamoyl]-7h-cyclopenta[d]pyrimidin-4-yl]amino]phenyl]methyl acetate Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)C3C4=C(C(=NC=N4)NC=4C=C(COC(C)=O)C=CC=4)C=C3)C(C)=CC=2)C=C1 KLMBMLLBCGFEKR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 2
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- LYZOGIUMCBXHNA-UHFFFAOYSA-N n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]-4-(3-prop-1-en-2-ylanilino)pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(=C)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)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)=C1 LYZOGIUMCBXHNA-UHFFFAOYSA-N 0.000 claims description 2
- UNZWZIXADXMVCK-UHFFFAOYSA-N n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]-4-(3-sulfamoylanilino)pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)S(N)(=O)=O)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 UNZWZIXADXMVCK-UHFFFAOYSA-N 0.000 claims description 2
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- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 101150025395 trkA gene Proteins 0.000 description 1
- 101150113435 trkA1 gene Proteins 0.000 description 1
- 102000047459 trkC Receptor Human genes 0.000 description 1
- 108010064892 trkC Receptor Proteins 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49853203P | 2003-08-28 | 2003-08-28 | |
| US60/498,532 | 2003-08-28 | ||
| PCT/US2004/027997 WO2005039486A2 (en) | 2003-08-28 | 2004-08-27 | Compounds and compositions as protein kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2536535A1 true CA2536535A1 (en) | 2005-05-06 |
Family
ID=34519982
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002536535A Abandoned CA2536535A1 (en) | 2003-08-28 | 2004-08-27 | Compounds and compositions as protein kinase inhibitors |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US7338957B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1658290A4 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2007504159A (cg-RX-API-DMAC7.html) |
| CN (1) | CN100439365C (cg-RX-API-DMAC7.html) |
| AU (1) | AU2004283093B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0414049A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2536535A1 (cg-RX-API-DMAC7.html) |
| MX (1) | MXPA06002347A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2005039486A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0202873D0 (en) * | 2002-02-07 | 2002-03-27 | Novartis Ag | Organic compounds |
| TW200616974A (en) * | 2004-07-01 | 2006-06-01 | Astrazeneca Ab | Chemical compounds |
| PL1891066T3 (pl) * | 2005-05-13 | 2011-05-31 | Irm Llc | Związki i kompozycje jako inhibitory kinazy białkowej |
| EP1999249B8 (en) * | 2006-03-30 | 2012-02-15 | The University Court Of The University of Edinburgh | Culture medium containing kinase inhibitors. and uses thereof |
| GB0615327D0 (en) | 2006-03-30 | 2006-09-13 | Univ Edinburgh | Culture medium containing kinase inhibitors and uses thereof |
| KR20090023561A (ko) | 2006-04-07 | 2009-03-05 | 노파르티스 아게 | ａ) 피리미딜아미노벤즈아미드 화합물과 ｂ) Ｔｈｒ３１５Ｉｌｅ 키나제 억제제를 포함하는 조합물 |
| WO2008147831A1 (en) * | 2007-05-23 | 2008-12-04 | Smithkline Beecham Corporation | Anthranilamides |
| CA2949336C (en) | 2007-08-02 | 2018-11-06 | Lei Zhu | Process for the synthesis of e1 activating enzyme inhibitors |
| WO2009020990A1 (en) * | 2007-08-08 | 2009-02-12 | Smithkline Beecham Corporation | 2- [ (2-{phenylamino}-1h-pyrrolo [2, 3-d] pyrimidin-4-yl) amino] benzamide derivatives as igf-1r inhibitors for the treatment of cancer |
| EA019869B1 (ru) * | 2007-11-28 | 2014-06-30 | Дана Фарбер Кансер Инститьют, Инк. | Низкомолекулярные миристатные ингибиторы тирозинкиназы bcr-abl и способы их применения |
| JP2011510004A (ja) * | 2008-01-22 | 2011-03-31 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | タンパク質キナーゼ阻害剤及びその使用 |
| PT2300013T (pt) | 2008-05-21 | 2017-10-31 | Ariad Pharma Inc | Derivados de fósforo como inibidores de cinases |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| UA108986C2 (uk) | 2009-05-14 | 2015-07-10 | Мілленніум Фармасьютікалз, Інк. | Кристалічна форма гідрохлориду ((1s,2s,4r)-4-{4-[(1s)-2,3-дигідро-1h-інден-1-іламіно]-7h-піроло[2,3-d]піримідин-7іл}-2-гідроксициклопентил)метилсульфамату (варіанти) |
| US8728763B2 (en) | 2009-08-11 | 2014-05-20 | Response Genetics | Methods, primers, probes and kits useful for the detection of BRAF mutations |
| EA201391626A1 (ru) | 2011-05-04 | 2014-03-31 | Ариад Фармасьютикалз, Инк. | Соединения для ингибирования клеточной пролиферации в egfr-стимулированных типах рака |
| AU2013204563B2 (en) | 2012-05-05 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| CN104876879B (zh) * | 2015-04-14 | 2018-05-18 | 中国科学院合肥物质科学研究院 | 一种bcr-abl激酶抑制剂 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT831829E (pt) * | 1995-06-07 | 2003-12-31 | Pfizer | Derivados de pirimidina heterociclicos de aneis fundidos |
| WO2000017203A1 (en) * | 1998-09-18 | 2000-03-30 | Basf Aktiengesellschaft | Pyrrolopyrimidines as protein kinase inhibitors |
| JP2003518123A (ja) * | 1999-12-21 | 2003-06-03 | スージェン・インコーポレーテッド | ４−置換７−アザ−インドリン−２−オンおよびその蛋白質キナーゼ阻害剤としての使用 |
| UA76977C2 (en) * | 2001-03-02 | 2006-10-16 | Icos Corp | Aryl- and heteroaryl substituted chk1 inhibitors and their use as radiosensitizers and chemosensitizers |
| WO2003009852A1 (en) * | 2001-07-24 | 2003-02-06 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
-
2004
- 2004-08-26 US US10/927,992 patent/US7338957B2/en not_active Expired - Fee Related
- 2004-08-27 BR BRPI0414049-4A patent/BRPI0414049A/pt not_active IP Right Cessation
- 2004-08-27 CN CNB2004800245751A patent/CN100439365C/zh not_active Expired - Fee Related
- 2004-08-27 AU AU2004283093A patent/AU2004283093B2/en not_active Ceased
- 2004-08-27 EP EP04816834A patent/EP1658290A4/en not_active Withdrawn
- 2004-08-27 JP JP2006524903A patent/JP2007504159A/ja active Pending
- 2004-08-27 WO PCT/US2004/027997 patent/WO2005039486A2/en not_active Ceased
- 2004-08-27 CA CA002536535A patent/CA2536535A1/en not_active Abandoned
- 2004-08-27 MX MXPA06002347A patent/MXPA06002347A/es active IP Right Grant
-
2008
- 2008-01-07 US US11/970,278 patent/US20080108616A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US7338957B2 (en) | 2008-03-04 |
| AU2004283093B2 (en) | 2009-02-26 |
| CN100439365C (zh) | 2008-12-03 |
| EP1658290A2 (en) | 2006-05-24 |
| CN1842529A (zh) | 2006-10-04 |
| AU2004283093A1 (en) | 2005-05-06 |
| BRPI0414049A (pt) | 2006-10-24 |
| WO2005039486A2 (en) | 2005-05-06 |
| EP1658290A4 (en) | 2009-04-15 |
| US20050159391A1 (en) | 2005-07-21 |
| WO2005039486A3 (en) | 2006-03-16 |
| MXPA06002347A (es) | 2006-05-19 |
| JP2007504159A (ja) | 2007-03-01 |
| US20080108616A1 (en) | 2008-05-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |