JPWO2020085493A5 - - Google Patents

Info

Publication number

JPWO2020085493A5

JPWO2020085493A5 JP2020552628A JP2020552628A JPWO2020085493A5 JP WO2020085493 A5 JPWO2020085493 A5 JP WO2020085493A5 JP 2020552628 A JP2020552628 A JP 2020552628A JP 2020552628 A JP2020552628 A JP 2020552628A JP WO2020085493 A5 JPWO2020085493 A5 JP WO2020085493A5

Authority

JP

Japan

Prior art keywords

group

chloro

amino

methyl

substituent

Prior art date

2019-10-25

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.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• 125000001424 substituent group Chemical group 0.000 claims 32
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 18
• 150000001875 compounds Chemical class 0.000 claims 18
• 150000003839 salts Chemical class 0.000 claims 17
• 125000000623 heterocyclic group Chemical group 0.000 claims 15
• 229910052757 nitrogen Inorganic materials 0.000 claims 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims 15
• 125000005843 halogen group Chemical group 0.000 claims 12
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 12
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims 10
• 125000004432 carbon atom Chemical group C* 0.000 claims 9
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 9
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 8
• 125000003277 amino group Chemical group 0.000 claims 8
• 229910052799 carbon Inorganic materials 0.000 claims 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 8
• -1 indazole compound Chemical class 0.000 claims 7
• 239000002246 antineoplastic agent Substances 0.000 claims 6
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims 5
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 4
• 125000004434 sulfur atom Chemical group 0.000 claims 4
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 3
• 125000005842 heteroatom Chemical group 0.000 claims 3
• 229910052717 sulfur Inorganic materials 0.000 claims 3
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
• 206010028980 Neoplasm Diseases 0.000 claims 2
• 239000004480 active ingredient Substances 0.000 claims 2
• 125000000217 alkyl group Chemical group 0.000 claims 2
• 125000000392 cycloalkenyl group Chemical group 0.000 claims 2
• 239000003814 drug Substances 0.000 claims 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
• 229960003552 other antineoplastic agent in atc Drugs 0.000 claims 2
• 125000004430 oxygen atom Chemical group O* 0.000 claims 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims 1
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 1
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims 1
• IUDHQFWNOROVRT-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-3,5-dimethyl-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC1=C(N(C(=N1)CNC2=NNC3=CC(=C(C=C32)C(C)(C)C)Cl)C)C(=O)NC4CN(C4)C(=O)C=C IUDHQFWNOROVRT-UHFFFAOYSA-N 0.000 claims 1
• IBWKULOISRIXMQ-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-(difluoromethyl)-3-(1-propan-2-ylpyrrolidin-3-yl)-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)N1CCC(C1)N2C(=NC(=C2C(=O)NC3CN(C3)C(=O)C=C)C(F)F)CNC4=NNC5=CC(=C(C=C54)C(C)(C)C)Cl IBWKULOISRIXMQ-UHFFFAOYSA-N 0.000 claims 1
• FEYJRULHFIDEST-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-(difluoromethyl)-3-propan-2-yl-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)N1C(=NC(=C1C(=O)NC2CN(C2)C(=O)C=C)C(F)F)CNC3=NNC4=CC(=C(C=C43)C(C)(C)C)Cl FEYJRULHFIDEST-UHFFFAOYSA-N 0.000 claims 1
• JFUYTUJBCLQYLF-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-(1-methylpiperidin-4-yl)-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)(C)C1=C(C=C2C(=C1)C(=NN2)NCC3=NC(=C(N3C4CCN(CC4)C)C(=O)NC5CN(C5)C(=O)C=C)Cl)Cl JFUYTUJBCLQYLF-UHFFFAOYSA-N 0.000 claims 1
• GCCIWPPELMCZMI-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-(1-propan-2-ylazetidin-3-yl)-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)N1CC(C1)N2C(=NC(=C2C(=O)NC3CN(C3)C(=O)C=C)Cl)CNC4=NNC5=CC(=C(C=C54)C(C)(C)C)Cl GCCIWPPELMCZMI-UHFFFAOYSA-N 0.000 claims 1
• LAGFOPGFUKKALV-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-(4-methoxycyclohexyl)-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)(C)C1=C(C=C2C(=C1)C(=NN2)NCC3=NC(=C(N3C4CCC(CC4)OC)C(=O)NC5CN(C5)C(=O)C=C)Cl)Cl LAGFOPGFUKKALV-UHFFFAOYSA-N 0.000 claims 1
• KSDNONFALPBINQ-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-(oxan-3-yl)-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)(C)C1=C(C=C2C(=C1)C(=NN2)NCC3=NC(=C(N3C4CCCOC4)C(=O)NC5CN(C5)C(=O)C=C)Cl)Cl KSDNONFALPBINQ-UHFFFAOYSA-N 0.000 claims 1
• FTNHKSSUKYUJEC-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-(oxan-4-yl)-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)(C)C1=C(C=C2C(=C1)C(=NN2)NCC3=NC(=C(N3C4CCOCC4)C(=O)NC5CN(C5)C(=O)C=C)Cl)Cl FTNHKSSUKYUJEC-UHFFFAOYSA-N 0.000 claims 1
• JKXRIABVROMSMG-NVXWUHKLSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-[(3R,5R)-1-(2,2-difluoroethyl)-5-methylpyrrolidin-3-yl]-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound C[C@@H]1C[C@H](CN1CC(F)F)N2C(=NC(=C2C(=O)NC3CN(C3)C(=O)C=C)Cl)CNC4=NNC5=CC(=C(C=C54)C(C)(C)C)Cl JKXRIABVROMSMG-NVXWUHKLSA-N 0.000 claims 1
• KXWASYCDTBXJSZ-INIZCTEOSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-[(3S)-1-(2,2-difluoroethyl)pyrrolidin-3-yl]-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)(C)C1=C(C=C2C(=C1)C(=NN2)NCC3=NC(=C(N3[C@H]4CCN(C4)CC(F)F)C(=O)NC5CN(C5)C(=O)C=C)Cl)Cl KXWASYCDTBXJSZ-INIZCTEOSA-N 0.000 claims 1
• NKHHRBCGFXJKAT-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-cyclopentyl-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)(C)C1=C(C=C2C(=C1)C(=NN2)NCC3=NC(=C(N3C4CCCC4)C(=O)NC5CN(C5)C(=O)C=C)Cl)Cl NKHHRBCGFXJKAT-UHFFFAOYSA-N 0.000 claims 1
• SSFDAWGOUVWMKB-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-methyl-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)(C)C1=C(C=C2C(=C1)C(=NN2)NCC3=NC(=C(N3C)C(=O)NC4CN(C4)C(=O)C=C)Cl)Cl SSFDAWGOUVWMKB-UHFFFAOYSA-N 0.000 claims 1
• ASAFUFALQACICI-ACJLOTCBSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-methyl-N-[(3R,4R)-4-methyl-1-prop-2-enoylpyrrolidin-3-yl]imidazole-4-carboxamide Chemical compound C[C@@H]1CN(C[C@@H]1NC(=O)C2=C(N=C(N2C)CNC3=NNC4=CC(=C(C=C43)C(C)(C)C)Cl)Cl)C(=O)C=C ASAFUFALQACICI-ACJLOTCBSA-N 0.000 claims 1
• OIWYBKKQVNNNQI-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-3-propan-2-yl-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC(C)N1C(=NC(=C1C(=O)NC2CN(C2)C(=O)C=C)Cl)CNC3=NNC4=CC(=C(C=C43)C(C)(C)C)Cl OIWYBKKQVNNNQI-UHFFFAOYSA-N 0.000 claims 1
• LXNPKRACAQWOCI-RDJZCZTQSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-chloro-N-[(3S,4S)-4-fluoro-1-prop-2-enoylpyrrolidin-3-yl]-3-methylimidazole-4-carboxamide Chemical compound CC(C)(C)C1=C(C=C2C(=C1)C(=NN2)NCC3=NC(=C(N3C)C(=O)N[C@H]4CN(C[C@@H]4F)C(=O)C=C)Cl)Cl LXNPKRACAQWOCI-RDJZCZTQSA-N 0.000 claims 1
• SRMJRHJSQYLHGC-RDJZCZTQSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-fluoro-N-[(3S,4S)-4-fluoro-1-prop-2-enoylpyrrolidin-3-yl]-3-methylimidazole-4-carboxamide Chemical compound CC(C)(C)C1=C(C=C2C(=C1)C(=NN2)NCC3=NC(=C(N3C)C(=O)N[C@H]4CN(C[C@@H]4F)C(=O)C=C)F)Cl SRMJRHJSQYLHGC-RDJZCZTQSA-N 0.000 claims 1
• DEVVVECNCNFWRN-UHFFFAOYSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-5-methyl-3-propan-2-yl-N-(1-prop-2-enoylazetidin-3-yl)imidazole-4-carboxamide Chemical compound CC1=C(N(C(=N1)CNC2=NNC3=CC(=C(C=C32)C(C)(C)C)Cl)C(C)C)C(=O)NC4CN(C4)C(=O)C=C DEVVVECNCNFWRN-UHFFFAOYSA-N 0.000 claims 1
• XCHLOIYRTYPUEH-HKUYNNGSSA-N 2-[[(5-tert-butyl-6-chloro-1H-indazol-3-yl)amino]methyl]-N-[(3S,4S)-4-fluoro-1-prop-2-enoylpyrrolidin-3-yl]-3,5-dimethylimidazole-4-carboxamide Chemical compound CC1=C(N(C(=N1)CNC2=NNC3=CC(=C(C=C32)C(C)(C)C)Cl)C)C(=O)N[C@H]4CN(C[C@@H]4F)C(=O)C=C XCHLOIYRTYPUEH-HKUYNNGSSA-N 0.000 claims 1
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
• 229940034982 antineoplastic agent Drugs 0.000 claims 1
• 229910052801 chlorine Inorganic materials 0.000 claims 1
• 125000001309 chloro group Chemical group Cl* 0.000 claims 1
• 125000000753 cycloalkyl group Chemical group 0.000 claims 1
• 229910052805 deuterium Inorganic materials 0.000 claims 1
• 125000004431 deuterium atom Chemical group 0.000 claims 1
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 1
• 150000002829 nitrogen Chemical class 0.000 claims 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1