TW201425307A - 作為激酶抑制劑之胺基－喹啉類 - Google Patents

Info

Publication number

TW201425307A

TW201425307A TW102132714A TW102132714A TW201425307A TW 201425307 A TW201425307 A TW 201425307A TW 102132714 A TW102132714 A TW 102132714A TW 102132714 A TW102132714 A TW 102132714A TW 201425307 A TW201425307 A TW 201425307A

Authority

TW

Taiwan

Prior art keywords

dimethyl

pyrazol

group

alkoxy

butylsulfonyl

Prior art date

2012-09-13

Links

• Espacenet
• Global Dossier
• Discuss

• 229940043355 kinase inhibitor Drugs 0.000 title description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
• 229940058934 aminoquinoline antimalarials Drugs 0.000 title 1
• 150000005010 aminoquinolines Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 221
• 150000003839 salts Chemical class 0.000 claims description 149
• -1 cyano, hydroxy Chemical group 0.000 claims description 87
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 50
• 102100022502 Receptor-interacting serine/threonine-protein kinase 2 Human genes 0.000 claims description 48
• 239000007787 solid Substances 0.000 claims description 48
• 101001109137 Homo sapiens Receptor-interacting serine/threonine-protein kinase 2 Proteins 0.000 claims description 47
• 201000010099 disease Diseases 0.000 claims description 47
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 47
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 46
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 46
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 42
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 38
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 34
• 239000008194 pharmaceutical composition Substances 0.000 claims description 34
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 29
• 125000005843 halogen group Chemical group 0.000 claims description 25
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 23
• 125000003545 alkoxy group Chemical group 0.000 claims description 23
• 230000001404 mediated effect Effects 0.000 claims description 23
• 239000003814 drug Substances 0.000 claims description 22
• 206010039491 Sarcoma Diseases 0.000 claims description 20
• 125000000217 alkyl group Chemical group 0.000 claims description 20
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• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 17
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 14
• 230000005764 inhibitory process Effects 0.000 claims description 13
• 125000001424 substituent group Chemical group 0.000 claims description 13
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 12
• 208000011231 Crohn disease Diseases 0.000 claims description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
• 208000009766 Blau syndrome Diseases 0.000 claims description 11
• 229910052736 halogen Inorganic materials 0.000 claims description 11
• QODPGRHWJBWTJC-UHFFFAOYSA-N 6-tert-butylsulfonyl-n-(4,5-dimethyl-1h-pyrazol-3-yl)-7-(2-methoxyethoxy)quinolin-4-amine Chemical compound C=12C=C(S(=O)(=O)C(C)(C)C)C(OCCOC)=CC2=NC=CC=1NC1=NNC(C)=C1C QODPGRHWJBWTJC-UHFFFAOYSA-N 0.000 claims description 10
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 10
• 206010037660 Pyrexia Diseases 0.000 claims description 10
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 10
• 206010046851 Uveitis Diseases 0.000 claims description 10
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
• 125000001153 fluoro group Chemical group F* 0.000 claims description 9
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• 150000001412 amines Chemical class 0.000 claims description 6
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• 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
• 238000002054 transplantation Methods 0.000 claims description 5
• VENUDGUYMCDYAB-UHFFFAOYSA-N 6-tert-butylsulfonyl-n-(4,5-dimethyl-1h-pyrazol-3-yl)-7-(3-methoxypropoxy)quinolin-4-amine Chemical compound C=12C=C(S(=O)(=O)C(C)(C)C)C(OCCCOC)=CC2=NC=CC=1NC1=NNC(C)=C1C VENUDGUYMCDYAB-UHFFFAOYSA-N 0.000 claims description 4
• 206010003827 Autoimmune hepatitis Diseases 0.000 claims description 4
• 208000029523 Interstitial Lung disease Diseases 0.000 claims description 4
• 206010069351 acute lung injury Diseases 0.000 claims description 4
• 229910052731 fluorine Inorganic materials 0.000 claims description 4
• 230000000302 ischemic effect Effects 0.000 claims description 4
• 201000006417 multiple sclerosis Diseases 0.000 claims description 4
• XCRPPAPDRUBKRJ-UHFFFAOYSA-N quinolin-7-ol Chemical compound C1=CC=NC2=CC(O)=CC=C21 XCRPPAPDRUBKRJ-UHFFFAOYSA-N 0.000 claims description 4
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
• HOTBTVYQQMHEBB-UHFFFAOYSA-N 1-[6-tert-butylsulfonyl-4-[(4,5-dimethyl-1h-pyrazol-3-yl)amino]quinolin-7-yl]oxy-2-methylpropan-2-ol Chemical compound CC1=C(C)NN=C1NC1=CC=NC2=CC(OCC(C)(C)O)=C(S(=O)(=O)C(C)(C)C)C=C12 HOTBTVYQQMHEBB-UHFFFAOYSA-N 0.000 claims description 3
• PLYPDBCKMUBDTF-UHFFFAOYSA-N 6-tert-butylsulfonyl-7-(2,2-difluoroethoxy)-n-(4,5-dimethyl-1h-pyrazol-3-yl)quinolin-4-amine Chemical compound CC1=C(C)NN=C1NC1=CC=NC2=CC(OCC(F)F)=C(S(=O)(=O)C(C)(C)C)C=C12 PLYPDBCKMUBDTF-UHFFFAOYSA-N 0.000 claims description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
• 208000009329 Graft vs Host Disease Diseases 0.000 claims description 3
• 206010063837 Reperfusion injury Diseases 0.000 claims description 3
• 239000011737 fluorine Substances 0.000 claims description 3
• 208000024908 graft versus host disease Diseases 0.000 claims description 3
• RONWGALEIBILOG-VMJVVOMYSA-N quinine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 RONWGALEIBILOG-VMJVVOMYSA-N 0.000 claims description 3
• 238000006467 substitution reaction Methods 0.000 claims description 3
• OVPZGUMHWDAVSH-UHFFFAOYSA-N 6-(2,2-dimethyloxan-4-yl)sulfonyl-n-(4,5-dimethyl-1h-pyrazol-3-yl)-7-methoxyquinolin-4-amine Chemical compound C=12C=C(S(=O)(=O)C3CC(C)(C)OCC3)C(OC)=CC2=NC=CC=1NC1=NNC(C)=C1C OVPZGUMHWDAVSH-UHFFFAOYSA-N 0.000 claims description 2
• DPSNWHXNCQBYAH-UHFFFAOYSA-N 6-tert-butylsulfonyl-7-methoxy-n-[4-methyl-5-(trifluoromethyl)-1h-pyrazol-3-yl]quinolin-4-amine Chemical compound C=12C=C(S(=O)(=O)C(C)(C)C)C(OC)=CC2=NC=CC=1NC1=NNC(C(F)(F)F)=C1C DPSNWHXNCQBYAH-UHFFFAOYSA-N 0.000 claims description 2
• LSBUSOIHRLJSJM-UHFFFAOYSA-N 6-tert-butylsulfonyl-n-(4,5-dimethyl-1h-pyrazol-3-yl)-7-(2,2,2-trifluoroethoxy)quinolin-4-amine Chemical compound CC1=C(C)NN=C1NC1=CC=NC2=CC(OCC(F)(F)F)=C(S(=O)(=O)C(C)(C)C)C=C12 LSBUSOIHRLJSJM-UHFFFAOYSA-N 0.000 claims description 2
• UVCJVWDOTPZNJM-UHFFFAOYSA-N 6-tert-butylsulfonyl-n-(4,5-dimethyl-1h-pyrazol-3-yl)-7-ethoxyquinolin-4-amine Chemical compound C=12C=C(S(=O)(=O)C(C)(C)C)C(OCC)=CC2=NC=CC=1NC1=NNC(C)=C1C UVCJVWDOTPZNJM-UHFFFAOYSA-N 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
• 239000000194 fatty acid Substances 0.000 claims description 2
• 229930195729 fatty acid Natural products 0.000 claims description 2
• 150000004665 fatty acids Chemical class 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims description 2
• ROPLCSFPUPWHGJ-UHFFFAOYSA-N hydroxycyanamide Chemical compound ONC#N ROPLCSFPUPWHGJ-UHFFFAOYSA-N 0.000 claims description 2
• ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Substances CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 2
• CXRQMMOWWNSBTM-UHFFFAOYSA-N n-(4,5-dimethyl-1h-pyrazol-3-yl)-7-methoxy-6-(oxan-4-ylsulfonyl)quinolin-4-amine Chemical compound C=12C=C(S(=O)(=O)C3CCOCC3)C(OC)=CC2=NC=CC=1NC1=NNC(C)=C1C CXRQMMOWWNSBTM-UHFFFAOYSA-N 0.000 claims description 2
• YZBBCCBLKFNURH-UHFFFAOYSA-N n-(4,5-dimethyl-1h-pyrazol-3-yl)-7-methoxy-6-propan-2-ylsulfonylquinolin-4-amine Chemical compound C=12C=C(S(=O)(=O)C(C)C)C(OC)=CC2=NC=CC=1NC1=NNC(C)=C1C YZBBCCBLKFNURH-UHFFFAOYSA-N 0.000 claims description 2
• DPILGXGHKJEOAS-UHFFFAOYSA-N 6-tert-butylsulfonyl-7-(difluoromethoxy)-n-(4,5-dimethyl-1h-pyrazol-3-yl)quinolin-4-amine Chemical compound CC1=C(C)NN=C1NC1=CC=NC2=CC(OC(F)F)=C(S(=O)(=O)C(C)(C)C)C=C12 DPILGXGHKJEOAS-UHFFFAOYSA-N 0.000 claims 1
• LHPFRDAGGDMRMZ-UHFFFAOYSA-N 6-tert-butylsulfonyl-n-(4,5-dimethyl-1h-pyrazol-3-yl)-7-methoxyquinolin-4-amine Chemical compound C=12C=C(S(=O)(=O)C(C)(C)C)C(OC)=CC2=NC=CC=1NC1=NNC(C)=C1C LHPFRDAGGDMRMZ-UHFFFAOYSA-N 0.000 claims 1
• SVARURAGDUBTCW-UHFFFAOYSA-N 7-(difluoromethoxy)-n-(4,5-dimethyl-1h-pyrazol-3-yl)-6-(oxan-4-ylsulfonyl)quinolin-4-amine Chemical compound CC1=C(C)NN=C1NC1=CC=NC2=CC(OC(F)F)=C(S(=O)(=O)C3CCOCC3)C=C12 SVARURAGDUBTCW-UHFFFAOYSA-N 0.000 claims 1
• GMWIWJMSCHALJV-UHFFFAOYSA-N 7-methoxy-n-[4-methyl-5-(trifluoromethyl)-1h-pyrazol-3-yl]-6-(oxan-4-ylsulfonyl)quinolin-4-amine Chemical compound C=12C=C(S(=O)(=O)C3CCOCC3)C(OC)=CC2=NC=CC=1NC1=NNC(C(F)(F)F)=C1C GMWIWJMSCHALJV-UHFFFAOYSA-N 0.000 claims 1
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• 238000000034 method Methods 0.000 abstract description 37
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