SK9062003A3 - Substituted triazole diamine derivatives as kinase inhibitors - Google Patents

Info

Publication number

SK9062003A3

SK9062003A3 SK906-2003A SK9062003A SK9062003A3 SK 9062003 A3 SK9062003 A3 SK 9062003A3 SK 9062003 A SK9062003 A SK 9062003A SK 9062003 A3 SK9062003 A3 SK 9062003A3

Authority

SK

Slovakia

Prior art keywords

alkyl

group

amino

substituted

substituents independently

Prior art date

2000-12-22

Links

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• -1 triazole diamine Chemical class 0.000 title claims abstract description 141
• 229940043355 kinase inhibitor Drugs 0.000 title abstract description 10
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
• 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 95
• 102000020233 phosphotransferase Human genes 0.000 claims abstract description 95
• 238000000034 method Methods 0.000 claims abstract description 70
• 230000001404 mediated effect Effects 0.000 claims abstract description 21
• 125000000217 alkyl group Chemical group 0.000 claims description 730
• 125000001424 substituent group Chemical group 0.000 claims description 496
• 150000001875 compounds Chemical class 0.000 claims description 325
• 229910052739 hydrogen Inorganic materials 0.000 claims description 289
• 239000001257 hydrogen Substances 0.000 claims description 262
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 242
• 125000001072 heteroaryl group Chemical group 0.000 claims description 222
• 125000003118 aryl group Chemical group 0.000 claims description 221
• 125000000623 heterocyclic group Chemical group 0.000 claims description 201
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 165
• 229910052799 carbon Inorganic materials 0.000 claims description 164
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 146
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 145
• 125000001475 halogen functional group Chemical group 0.000 claims description 120
• 125000003545 alkoxy group Chemical group 0.000 claims description 112
• 150000002431 hydrogen Chemical class 0.000 claims description 101
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 100
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 100
• 125000003277 amino group Chemical group 0.000 claims description 92
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 89
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 88
• 125000003342 alkenyl group Chemical group 0.000 claims description 83
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 65
• 125000000304 alkynyl group Chemical group 0.000 claims description 51
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
• 125000003282 alkyl amino group Chemical group 0.000 claims description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
• 201000010099 disease Diseases 0.000 claims description 24
• 150000003839 salts Chemical class 0.000 claims description 24
• 238000011282 treatment Methods 0.000 claims description 22
• 108010034798 CDC2 Protein Kinase Proteins 0.000 claims description 21
• 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 claims description 21
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims description 21
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 21
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 21
• 206010028980 Neoplasm Diseases 0.000 claims description 18
• 230000005764 inhibitory process Effects 0.000 claims description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims description 18
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 17
• 230000009977 dual effect Effects 0.000 claims description 17
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 16
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 16
• 125000004076 pyridyl group Chemical group 0.000 claims description 16
• KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 15
• 239000002246 antineoplastic agent Substances 0.000 claims description 15
• 125000001544 thienyl group Chemical group 0.000 claims description 15
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 14
• 239000003795 chemical substances by application Substances 0.000 claims description 12
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• 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 claims description 10
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• 230000001419 dependent effect Effects 0.000 claims description 9
• 125000000335 thiazolyl group Chemical group 0.000 claims description 9
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• 239000003937 drug carrier Substances 0.000 claims description 8
• YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims description 8
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
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• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 6
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• 125000004193 piperazinyl group Chemical group 0.000 claims description 6
• 102000005962 receptors Human genes 0.000 claims description 6
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• 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000002541 furyl group Chemical group 0.000 claims description 5
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
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• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
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• 125000001425 triazolyl group Chemical group 0.000 claims description 4
• 230000004614 tumor growth Effects 0.000 claims description 4
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• 125000005605 benzo group Chemical group 0.000 claims description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
• ANRUFEHVGOBQPO-UHFFFAOYSA-N 4-[[5-amino-1-(2,6-difluoro-3-methylbenzoyl)-1,2,4-triazol-3-yl]amino]-n-methylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC)=CC=C1NC1=NN(C(=O)C=2C(=C(C)C=CC=2F)F)C(N)=N1 ANRUFEHVGOBQPO-UHFFFAOYSA-N 0.000 claims description 2
• VVGOTCALTHQXFY-UHFFFAOYSA-N 4-[[5-amino-1-(2-chloro-6-fluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide Chemical compound N=1N(C(=O)C=2C(=CC=CC=2F)Cl)C(N)=NC=1NC1=CC=C(S(N)(=O)=O)C=C1 VVGOTCALTHQXFY-UHFFFAOYSA-N 0.000 claims description 2
• YWMVKBOCDJSIMY-UHFFFAOYSA-N 4-[[5-amino-1-(3-methylthiophene-2-carbonyl)-1,2,4-triazol-3-yl]amino]-n-methylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC)=CC=C1NC1=NN(C(=O)C2=C(C=CS2)C)C(N)=N1 YWMVKBOCDJSIMY-UHFFFAOYSA-N 0.000 claims description 2
• ARIOBGGRZJITQX-UHFFFAOYSA-N 5-amino-3-{[4-(aminosulfonyl)phenyl]amino}-n-(2,6-difluorophenyl)-1h-1,2,4-triazole-1-carbothioamide Chemical compound N=1N(C(=S)NC=2C(=CC=CC=2F)F)C(N)=NC=1NC1=CC=C(S(N)(=O)=O)C=C1 ARIOBGGRZJITQX-UHFFFAOYSA-N 0.000 claims description 2
• JBOXDNIWQACYPW-UHFFFAOYSA-N 5-amino-n-(2,6-difluorophenyl)-3-(4-sulfamoylanilino)-1,2,4-triazole-1-carboxamide Chemical compound N=1N(C(=O)NC=2C(=CC=CC=2F)F)C(N)=NC=1NC1=CC=C(S(N)(=O)=O)C=C1 JBOXDNIWQACYPW-UHFFFAOYSA-N 0.000 claims description 2
• CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 2
• KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 2
• 238000002512 chemotherapy Methods 0.000 claims description 2
• 208000022605 chemotherapy-induced alopecia Diseases 0.000 claims description 2
• 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims 4
• 108010034265 Vascular Endothelial Growth Factor Receptors Proteins 0.000 claims 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
• ZUNASHLZAWVKEM-UHFFFAOYSA-N 4-[[5-amino-1-(2-chloro-6-fluoro-3-methylbenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide Chemical compound CC1=CC=C(F)C(C(=O)N2C(=NC(NC=3C=CC(=CC=3)S(N)(=O)=O)=N2)N)=C1Cl ZUNASHLZAWVKEM-UHFFFAOYSA-N 0.000 claims 1
• 102000009024 Epidermal Growth Factor Human genes 0.000 claims 1
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• KUANYBUVVODAIC-UHFFFAOYSA-N NC1=NC(=NN1C(=O)OC=1SC=CC1C)NC1=CC=C(C=C1)S(=O)(=O)NC1=NC=CC=C1 Chemical compound NC1=NC(=NN1C(=O)OC=1SC=CC1C)NC1=CC=C(C=C1)S(=O)(=O)NC1=NC=CC=C1 KUANYBUVVODAIC-UHFFFAOYSA-N 0.000 claims 1
• 229940116977 epidermal growth factor Drugs 0.000 claims 1
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
• 238000001959 radiotherapy Methods 0.000 claims 1
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims 1
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