HRP20030844A2 - Novel tyrosine kinase inhibitors - Google Patents

Info

Publication number

HRP20030844A2

HRP20030844A2 HR20030844A HRP20030844A HRP20030844A2 HR P20030844 A2 HRP20030844 A2 HR P20030844A2 HR 20030844 A HR20030844 A HR 20030844A HR P20030844 A HRP20030844 A HR P20030844A HR P20030844 A2 HRP20030844 A2 HR P20030844A2

Authority

HR

Croatia

Prior art keywords

methyl

pyridin

hydroxy

ethylamino

phenyl

Prior art date

2001-03-28

Links

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• 239000005483 tyrosine kinase inhibitor Substances 0.000 title description 5
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 title description 5
• 229910052739 hydrogen Inorganic materials 0.000 claims description 936
• 150000001875 compounds Chemical class 0.000 claims description 158
• 239000001257 hydrogen Substances 0.000 claims description 110
• 125000000217 alkyl group Chemical group 0.000 claims description 87
• -1 sulfoxy, sulfonyl Chemical group 0.000 claims description 80
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 77
• 150000002431 hydrogen Chemical class 0.000 claims description 76
• 125000001072 heteroaryl group Chemical group 0.000 claims description 57
• 238000000034 method Methods 0.000 claims description 57
• 229910052736 halogen Inorganic materials 0.000 claims description 56
• 150000002367 halogens Chemical class 0.000 claims description 56
• 125000003118 aryl group Chemical group 0.000 claims description 54
• 125000003545 alkoxy group Chemical group 0.000 claims description 50
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 45
• 125000003342 alkenyl group Chemical group 0.000 claims description 43
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 38
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 32
• 125000005309 thioalkoxy group Chemical group 0.000 claims description 32
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 29
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 27
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 26
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 23
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
• 206010028980 Neoplasm Diseases 0.000 claims description 21
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 21
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 21
• 125000000304 alkynyl group Chemical group 0.000 claims description 21
• 229910052731 fluorine Inorganic materials 0.000 claims description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims description 18
• 201000011510 cancer Diseases 0.000 claims description 16
• 238000011282 treatment Methods 0.000 claims description 16
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 14
• 229910052794 bromium Inorganic materials 0.000 claims description 13
• 239000000460 chlorine Substances 0.000 claims description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
• 150000003839 salts Chemical class 0.000 claims description 13
• 125000001424 substituent group Chemical class 0.000 claims description 13
• 125000003282 alkyl amino group Chemical group 0.000 claims description 12
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 12
• 229910052760 oxygen Inorganic materials 0.000 claims description 12
• 229910052717 sulfur Inorganic materials 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
• 241000124008 Mammalia Species 0.000 claims description 10
• 239000003112 inhibitor Substances 0.000 claims description 10
• 229910052799 carbon Inorganic materials 0.000 claims description 9
• 229910052801 chlorine Inorganic materials 0.000 claims description 9
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 9
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
• ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical compound C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 claims description 8
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 8
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 8
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 8
• 239000002246 antineoplastic agent Substances 0.000 claims description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
• 229940002612 prodrug Drugs 0.000 claims description 8
• 239000000651 prodrug Substances 0.000 claims description 8
• 125000001316 cycloalkyl alkyl group Chemical group 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
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 7
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
• UIUYQDFIVJOTTH-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-(4-methyl-6-piperazin-1-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCNCC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 UIUYQDFIVJOTTH-UHFFFAOYSA-N 0.000 claims description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
• 150000002780 morpholines Chemical class 0.000 claims description 6
• FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 5
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
• 229940022353 herceptin Drugs 0.000 claims description 5
• XPTAUSRPHWOZPN-UHFFFAOYSA-N morpholin-4-yl hydrogen sulfate Chemical group OS(=O)(=O)ON1CCOCC1 XPTAUSRPHWOZPN-UHFFFAOYSA-N 0.000 claims description 5
• 230000002062 proliferating effect Effects 0.000 claims description 5
• OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 claims description 4
• WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 claims description 4
• QEDRKDBUNJAFMZ-UHFFFAOYSA-N 2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazole-5-carbonitrile Chemical compound N=1C=2C(C)=CC(C#N)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 QEDRKDBUNJAFMZ-UHFFFAOYSA-N 0.000 claims description 4
• OTOIUCLFSQHFOX-UHFFFAOYSA-N 3-sulfonylmorpholine Chemical group O=S(=O)=C1COCCN1 OTOIUCLFSQHFOX-UHFFFAOYSA-N 0.000 claims description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 4
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 4
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 4
• 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 4
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 4
• HZQLLKQPXMHIMZ-UHFFFAOYSA-N N-[1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]-2-fluoroacetamide Chemical compound N=1C=2C(C)=CC(N3CCC(CC3)NC(=O)CF)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 HZQLLKQPXMHIMZ-UHFFFAOYSA-N 0.000 claims description 4
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 4
• 229930012538 Paclitaxel Natural products 0.000 claims description 4
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 4
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 4
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 4
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 4
• 239000004037 angiogenesis inhibitor Substances 0.000 claims description 4
• 229940121369 angiogenesis inhibitor Drugs 0.000 claims description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 4
• 229960004316 cisplatin Drugs 0.000 claims description 4
• 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 claims description 4
• 229960004679 doxorubicin Drugs 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 229930013356 epothilone Natural products 0.000 claims description 4
• 229960001433 erlotinib Drugs 0.000 claims description 4
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 4
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 4
• 229960005420 etoposide Drugs 0.000 claims description 4
• 239000011737 fluorine Substances 0.000 claims description 4
• 229960002949 fluorouracil Drugs 0.000 claims description 4
• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 4
• 125000001188 haloalkyl group Chemical group 0.000 claims description 4
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
• 150000004677 hydrates Chemical class 0.000 claims description 4
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 4
• 229940084651 iressa Drugs 0.000 claims description 4
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 229960000485 methotrexate Drugs 0.000 claims description 4
• 125000002950 monocyclic group Chemical group 0.000 claims description 4
• 229960001592 paclitaxel Drugs 0.000 claims description 4
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 239000012453 solvate Substances 0.000 claims description 4
• 229960001603 tamoxifen Drugs 0.000 claims description 4
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 4
• 229960000303 topotecan Drugs 0.000 claims description 4
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 4
• 239000002525 vasculotropin inhibitor Substances 0.000 claims description 4
• WDELNBOQCPAGPI-KRWDZBQOSA-N (2s)-2-[[6-chloro-5-(6-imidazol-1-yl-4-methyl-1h-benzimidazol-2-yl)pyrimidin-4-yl]amino]-3-phenylpropan-1-ol Chemical compound C([C@@H](CO)NC1=NC=NC(Cl)=C1C=1NC=2C=C(C=C(C=2N=1)C)N1C=NC=C1)C1=CC=CC=C1 WDELNBOQCPAGPI-KRWDZBQOSA-N 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
• VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 3
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 3
• HHGVGFMWJQKOFG-KRWDZBQOSA-N 2-[4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazole-5-carbonitrile Chemical compound C([C@@H](CO)NC1=C(C(NC=C1)=O)C=1NC=2C=C(C=C(C=2N=1)C)C#N)C1=CC=CC=C1 HHGVGFMWJQKOFG-KRWDZBQOSA-N 0.000 claims description 3
• QIEKBURWQYYQLT-UHFFFAOYSA-N 3-[6-(4-acetylpiperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-1H-pyridin-2-one Chemical compound C1CN(C(=O)C)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 QIEKBURWQYYQLT-UHFFFAOYSA-N 0.000 claims description 3
• WGKQPIGFIPWZNV-KRWDZBQOSA-N 4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-5-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyrimidin-6-one Chemical compound C([C@@H](CO)NC1=C(C(NC=N1)=O)C=1NC=2C=C(C=C(C=2N=1)C)N1C=NC=C1)C1=CC=CC=C1 WGKQPIGFIPWZNV-KRWDZBQOSA-N 0.000 claims description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 3
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims description 3
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
• VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical group F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 3
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
• OTXBWGUYZNKPMG-UHFFFAOYSA-N isofulminic acid Chemical compound O[N+]#[C-] OTXBWGUYZNKPMG-UHFFFAOYSA-N 0.000 claims description 3
• 229940127084 other anti-cancer agent Drugs 0.000 claims description 3
• LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 claims description 2
• LWELCYJSAYQTOX-UHFFFAOYSA-N 1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]-N-(2-fluoroethoxy)piperidine-4-carboxamide Chemical compound N=1C=2C(C)=CC(N3CCC(CC3)C(=O)NOCCF)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 LWELCYJSAYQTOX-UHFFFAOYSA-N 0.000 claims description 2
• ZLEMMUBHALJEGB-UHFFFAOYSA-N 1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]-N-(2-methoxyethoxy)piperidine-4-carboxamide Chemical compound C1CC(C(=O)NOCCOC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 ZLEMMUBHALJEGB-UHFFFAOYSA-N 0.000 claims description 2
• WKJBSMLANQKUCC-UHFFFAOYSA-N 1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]-N-methoxypiperidine-4-carboxamide Chemical compound C1CC(C(=O)NOC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 WKJBSMLANQKUCC-UHFFFAOYSA-N 0.000 claims description 2
• IFNWESYYDINUHV-UHFFFAOYSA-N 2,6-dimethylpiperazine Chemical group CC1CNCC(C)N1 IFNWESYYDINUHV-UHFFFAOYSA-N 0.000 claims description 2
• BXPWYRZCEDJCQW-GOSISDBHSA-N 2-[4-[[(2S)-2-hydroxy-2-phenylethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazole-5-carbonitrile Chemical compound C1([C@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)C#N)=CC=CC=C1 BXPWYRZCEDJCQW-GOSISDBHSA-N 0.000 claims description 2
• LQEBRSGCLFNPHN-UHFFFAOYSA-N 2-[4-[[2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazole-5-carbonitrile Chemical compound C1=C(Br)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)C#N)C(=O)NC=C1 LQEBRSGCLFNPHN-UHFFFAOYSA-N 0.000 claims description 2
• YETIHONGYJNLSF-UHFFFAOYSA-N 2-[4-[[2-(3-bromophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazole-5-carbonitrile Chemical compound N=1C=2C(C)=CC(C#N)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Br)=C1 YETIHONGYJNLSF-UHFFFAOYSA-N 0.000 claims description 2
• BKOVQGMNMPRQPP-UHFFFAOYSA-N 2-[4-[[2-(3-fluorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazole-5-carbonitrile Chemical compound N=1C=2C(C)=CC(C#N)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(F)=C1 BKOVQGMNMPRQPP-UHFFFAOYSA-N 0.000 claims description 2
• 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
• JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical group CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 claims description 2
• COZVWKMJBNLADG-HNNXBMFYSA-N 3-(1H-benzimidazol-2-yl)-4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-1H-pyridin-2-one Chemical compound C([C@@H](CO)NC1=C(C(=O)NC=C1)C=1NC2=CC=CC=C2N=1)C1=CC=CC=C1 COZVWKMJBNLADG-HNNXBMFYSA-N 0.000 claims description 2
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• AMJILRTVLRYXLQ-HXUWFJFHSA-N 4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1([C@@H](CO)NC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C=NC=C2)=CC=CC=C1 AMJILRTVLRYXLQ-HXUWFJFHSA-N 0.000 claims description 2
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• RHIFVNRZXJLERW-QFIPXVFZSA-N 4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-3-[4-methyl-6-(4-propan-2-ylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CN(C(C)C)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3N[C@H](CO)CC=3C=CC=CC=3)=O)C2=C1 RHIFVNRZXJLERW-QFIPXVFZSA-N 0.000 claims description 2
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• XSHAQUDGMYHMSJ-JOCHJYFZSA-N 4-[[(2S)-2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCN(C)CC2)C(=O)NC=C1 XSHAQUDGMYHMSJ-JOCHJYFZSA-N 0.000 claims description 2
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• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
• UHCBBWUQDAVSMS-UHFFFAOYSA-N fluoroethane Chemical group CCF UHCBBWUQDAVSMS-UHFFFAOYSA-N 0.000 claims 2
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 2
• BKRADANXACAJKT-UHFFFAOYSA-N 2-[4-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazin-1-yl]acetonitrile Chemical compound N=1C=2C(C)=CC(N3CCN(CC#N)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 BKRADANXACAJKT-UHFFFAOYSA-N 0.000 claims 1
• NQRCKUVJMDFGCB-KRWDZBQOSA-N 2-[4-[[(2S)-1-(3-chlorophenyl)-3-hydroxypropan-2-yl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazole-5-carbonitrile Chemical compound C([C@@H](CO)NC1=C(C(NC=C1)=O)C=1NC=2C=C(C=C(C=2N=1)C)C#N)C1=CC=CC(Cl)=C1 NQRCKUVJMDFGCB-KRWDZBQOSA-N 0.000 claims 1
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 1
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims 1
• NIAVSXKTUHEZFR-UHFFFAOYSA-N 2-fluoroethyl 4-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazine-1-carboxylate Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)OCCF)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 NIAVSXKTUHEZFR-UHFFFAOYSA-N 0.000 claims 1
• GDFPWAFEENMXSX-UHFFFAOYSA-N 2-methoxyethyl 4-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCCOC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 GDFPWAFEENMXSX-UHFFFAOYSA-N 0.000 claims 1
• VVIPLSCLYCWUQT-UHFFFAOYSA-N 3-[4-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazin-1-yl]propanenitrile Chemical compound N=1C=2C(C)=CC(N3CCN(CCC#N)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 VVIPLSCLYCWUQT-UHFFFAOYSA-N 0.000 claims 1
• TUZKEXPUYPJNDF-UHFFFAOYSA-N 3-[6-(4-acetylpiperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-4-[[2-(3-bromophenyl)-2-hydroxyethyl]amino]-1H-pyridin-2-one Chemical compound C1CN(C(=O)C)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Br)C=CC=3)=O)C2=C1 TUZKEXPUYPJNDF-UHFFFAOYSA-N 0.000 claims 1
• DVSOQVVEQNAVNQ-QHCPKHFHSA-N 3-[6-(4-butylpiperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-1H-pyridin-2-one Chemical compound C1CN(CCCC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3N[C@H](CO)CC=3C=CC=CC=3)=O)C2=C1 DVSOQVVEQNAVNQ-QHCPKHFHSA-N 0.000 claims 1
• HGDHHEZBLVABGA-UHFFFAOYSA-N 3-[6-[4-(2-chloroacetyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)CCl)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 HGDHHEZBLVABGA-UHFFFAOYSA-N 0.000 claims 1
• XXVGYZJJJDYLCD-IBGZPJMESA-N 4-[2-[4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazine-1-carboxamide Chemical compound C([C@@H](CO)NC1=C(C(NC=C1)=O)C=1NC=2C=C(C=C(C=2N=1)C)N1CCN(CC1)C(N)=O)C1=CC=CC=C1 XXVGYZJJJDYLCD-IBGZPJMESA-N 0.000 claims 1
• LQRBWXDBMNHGCK-FQEVSTJZSA-N 4-[[(2R)-2-hydroxy-2-phenylethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1([C@@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C=NC=C2)=CC=CC=C1 LQRBWXDBMNHGCK-FQEVSTJZSA-N 0.000 claims 1
• XBNXAXRVKFHSSL-QFIPXVFZSA-N 4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-3-[4-methyl-6-(2-morpholin-4-ylethylamino)-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C=1C=2NC(C=3C(NC=CC=3N[C@H](CO)CC=3C=CC=CC=3)=O)=NC=2C(C)=CC=1NCCN1CCOCC1 XBNXAXRVKFHSSL-QFIPXVFZSA-N 0.000 claims 1
• DWXRRSODJNHKQF-FQEVSTJZSA-N 4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-3-[4-methyl-6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CN(C)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3N[C@H](CO)CC=3C=CC=CC=3)=O)C2=C1 DWXRRSODJNHKQF-FQEVSTJZSA-N 0.000 claims 1
• SQNXDJMPLAKIID-HXUWFJFHSA-N 4-[[(2S)-2-(3-bromophenyl)-2-hydroxyethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1([C@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C=NC=C2)=CC=CC(Br)=C1 SQNXDJMPLAKIID-HXUWFJFHSA-N 0.000 claims 1
• PUHIHKJDRCRYTD-OAQYLSRUSA-N 4-[[(2S)-2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-(5,6-dihydro-4H-pyrimidin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Cl)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2C=NCCC2)C(=O)NC=C1 PUHIHKJDRCRYTD-OAQYLSRUSA-N 0.000 claims 1
• AATRIKZDGKCSFA-GAJHUEQPSA-N 4-[[(2S)-2-(7-bromo-2,3-dihydro-1-benzofuran-4-yl)-2-hydroxyethyl]amino]-3-[6-[(2R)-2-(fluoromethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C=1C=2NC(C=3C(NC=CC=3NC[C@@H](O)C=3C=4CCOC=4C(Br)=CC=3)=O)=NC=2C(C)=CC=1N1CCO[C@@H](CF)C1 AATRIKZDGKCSFA-GAJHUEQPSA-N 0.000 claims 1
• LQRBWXDBMNHGCK-HXUWFJFHSA-N 4-[[(2S)-2-hydroxy-2-phenylethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1([C@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C=NC=C2)=CC=CC=C1 LQRBWXDBMNHGCK-HXUWFJFHSA-N 0.000 claims 1
• MDBNOVPXWFLVKY-UHFFFAOYSA-N 4-[[2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2C=NC=C2)C(=O)NC=C1 MDBNOVPXWFLVKY-UHFFFAOYSA-N 0.000 claims 1
• PZSACZRLMBGKSF-VEXWJQHLSA-N 4-[[2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[(2S)-2-morpholin-4-ylpropoxy]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound BrC=1C=C(C=CC1OC)C(CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)OC[C@H](C)N2CCOCC2)O PZSACZRLMBGKSF-VEXWJQHLSA-N 0.000 claims 1
• IMMXVSIPHLGTTG-UHFFFAOYSA-N 4-[[2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoropropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCN(CCCF)CC2)C(=O)NC=C1 IMMXVSIPHLGTTG-UHFFFAOYSA-N 0.000 claims 1
• FKXIIIPVPAGWFJ-UHFFFAOYSA-N 4-[[2-(3-bromophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2-hydroxyethyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCO)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Br)=C1 FKXIIIPVPAGWFJ-UHFFFAOYSA-N 0.000 claims 1
• MQPZCABORBJAFW-UHFFFAOYSA-N 4-[[2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl]amino]-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCOCC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=C(F)C(Cl)=C1 MQPZCABORBJAFW-UHFFFAOYSA-N 0.000 claims 1
• MQKSVRLGJFYTRI-UHFFFAOYSA-N 4-[[2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl]amino]-3-(4-methyl-6-piperazin-1-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCNCC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=C(F)C(Cl)=C1 MQKSVRLGJFYTRI-UHFFFAOYSA-N 0.000 claims 1
• LGLHDKFGXZEGKW-UHFFFAOYSA-N 4-[[2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoropropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCCF)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=C(F)C(Cl)=C1 LGLHDKFGXZEGKW-UHFFFAOYSA-N 0.000 claims 1
• IYAZTZOPWLFGSM-UHFFFAOYSA-N 4-[[2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1=C(Cl)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCOCC2)C(=O)NC=C1 IYAZTZOPWLFGSM-UHFFFAOYSA-N 0.000 claims 1
• VTMIHYCOXBGSOX-UHFFFAOYSA-N 4-[[2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoropropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Cl)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCN(CCCF)CC2)C(=O)NC=C1 VTMIHYCOXBGSOX-UHFFFAOYSA-N 0.000 claims 1
• ZEBVMFXVTKXQJX-VEXWJQHLSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[(2S)-2-morpholin-4-ylpropoxy]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound ClC=1C=C(C=CC1)C(CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)OC[C@H](C)N2CCOCC2)O ZEBVMFXVTKXQJX-VEXWJQHLSA-N 0.000 claims 1
• BPAKRUQJYIEQNO-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(2-methylsulfanylacetyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CN(C(=O)CSC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 BPAKRUQJYIEQNO-UHFFFAOYSA-N 0.000 claims 1
• INGPCXNUMNHUML-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(2-methylsulfinylacetyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)CS(C)=O)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 INGPCXNUMNHUML-UHFFFAOYSA-N 0.000 claims 1
• ODKOFIIUMZVPOY-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(2-methylsulfonylacetyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)CS(C)(=O)=O)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 ODKOFIIUMZVPOY-UHFFFAOYSA-N 0.000 claims 1
• IAOSNXWODOEZQA-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(2-methylsulfonylethyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCS(C)(=O)=O)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 IAOSNXWODOEZQA-UHFFFAOYSA-N 0.000 claims 1
• UIBLHEZWESDKHO-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(2-thiomorpholin-4-ylacetyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)CN3CCSCC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 UIBLHEZWESDKHO-UHFFFAOYSA-N 0.000 claims 1
• QLBZNPSNLVNWIT-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(3,3,3-trifluoropropyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCC(F)(F)F)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 QLBZNPSNLVNWIT-UHFFFAOYSA-N 0.000 claims 1
• BDECAGGTSQFWTL-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(3,4,4-trifluorobut-3-enyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCC(F)=C(F)F)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 BDECAGGTSQFWTL-UHFFFAOYSA-N 0.000 claims 1
• BRXYAENMEBTBTN-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-(4-ethylpiperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CN(CC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 BRXYAENMEBTBTN-UHFFFAOYSA-N 0.000 claims 1
• VQPODECQMREPQU-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2,2-difluoroacetyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)C(F)F)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 VQPODECQMREPQU-UHFFFAOYSA-N 0.000 claims 1
• ZAKBVBOEYCRZJE-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2-fluoroethyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCF)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 ZAKBVBOEYCRZJE-UHFFFAOYSA-N 0.000 claims 1
• ODZVOOVRXLCZEN-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2-hydroxy-2-methylpropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC(C)(C)O)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 ODZVOOVRXLCZEN-UHFFFAOYSA-N 0.000 claims 1
• IHQMLJBDDJVMHI-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2-hydroxyethyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCO)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 IHQMLJBDDJVMHI-UHFFFAOYSA-N 0.000 claims 1
• UXGODHMBZZMTNL-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2-methoxyacetyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CN(C(=O)COC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 UXGODHMBZZMTNL-UHFFFAOYSA-N 0.000 claims 1
• DWYUYEUFJJPGLV-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoro-2-hydroxypropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC(O)CF)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 DWYUYEUFJJPGLV-UHFFFAOYSA-N 0.000 claims 1
• VUVAXIBXIAPBBM-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoropropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCCF)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 VUVAXIBXIAPBBM-UHFFFAOYSA-N 0.000 claims 1
• KKACLEOGRMSWFM-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(4-fluorobutanoyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)CCCF)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 KKACLEOGRMSWFM-UHFFFAOYSA-N 0.000 claims 1
• GHIBXMDVXCYMIY-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-5-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyrimidin-6-one Chemical compound N=1C=2C(C)=CC(N3C=NC=C3)=CC=2NC=1C(C(NC=N1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 GHIBXMDVXCYMIY-UHFFFAOYSA-N 0.000 claims 1
• SJEQKFKYXGQTRS-UHFFFAOYSA-N 4-[[2-(7-bromo-2,3-dihydro-1-benzofuran-5-yl)-2-hydroxyethyl]amino]-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C=1C=2NC(C=3C(NC=CC=3NCC(O)C=3C=C(Br)C=4OCCC=4C=3)=O)=NC=2C(C)=CC=1N1CCOCC1 SJEQKFKYXGQTRS-UHFFFAOYSA-N 0.000 claims 1
• 229940125497 HER2 kinase inhibitor Drugs 0.000 claims 1
• 125000005122 aminoalkylamino group Chemical group 0.000 claims 1
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