JP2020521740A5 - - Google Patents

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Publication number

JP2020521740A5

JP2020521740A5 JP2019564453A JP2019564453A JP2020521740A5 JP 2020521740 A5 JP2020521740 A5 JP 2020521740A5 JP 2019564453 A JP2019564453 A JP 2019564453A JP 2019564453 A JP2019564453 A JP 2019564453A JP 2020521740 A5 JP2020521740 A5 JP 2020521740A5

Authority

JP

Japan

Prior art keywords

alkyl

compound according

aminyl

halo

cycloalkyl

Prior art date

2018-05-24

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.)

Pending

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• 150000001875 compounds Chemical class 0.000 claims description 77
• 125000000623 heterocyclic group Chemical group 0.000 claims description 33
• -1 C 1 to C 6 alkyl Chemical group 0.000 claims description 26
• 125000000217 alkyl group Chemical group 0.000 claims description 26
• 125000005843 halogen group Chemical group 0.000 claims description 20
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 206010028980 Neoplasm Diseases 0.000 claims description 16
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 16
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 16
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 15
• 125000002837 carbocyclic group Chemical group 0.000 claims description 14
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
• 125000003118 aryl group Chemical group 0.000 claims description 12
• 201000011510 cancer Diseases 0.000 claims description 12
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 12
• 125000001188 haloalkyl group Chemical group 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• 125000000304 alkynyl group Chemical group 0.000 claims description 9
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 9
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
• 125000001153 fluoro group Chemical group F* 0.000 claims description 8
• 125000001424 substituent group Chemical group 0.000 claims description 8
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
• 102200124918 rs121913250 Human genes 0.000 claims description 5
• HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 claims description 4
• 206010027476 Metastases Diseases 0.000 claims description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
• 125000002947 alkylene group Chemical group 0.000 claims description 4
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• 230000001404 mediated effect Effects 0.000 claims description 4
• 230000009401 metastasis Effects 0.000 claims description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• 125000004043 oxo group Chemical group O=* 0.000 claims description 4
• 206010009944 Colon cancer Diseases 0.000 claims description 3
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
• 201000005787 hematologic cancer Diseases 0.000 claims description 3
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 3
• 201000005202 lung cancer Diseases 0.000 claims description 3
• 208000020816 lung neoplasm Diseases 0.000 claims description 3
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
• 230000035772 mutation Effects 0.000 claims description 3
• 201000002528 pancreatic cancer Diseases 0.000 claims description 3
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
• 102200006614 rs104894229 Human genes 0.000 claims description 3
• 102200006538 rs121913530 Human genes 0.000 claims description 3
• 102100029974 GTPase HRas Human genes 0.000 claims description 2
• 102100030708 GTPase KRas Human genes 0.000 claims description 2
• 101000584633 Homo sapiens GTPase HRas Proteins 0.000 claims description 2
• 101000584612 Homo sapiens GTPase KRas Proteins 0.000 claims description 2
• 102000008300 Mutant Proteins Human genes 0.000 claims description 2
• 108010021466 Mutant Proteins Proteins 0.000 claims description 2
• 229910019142 PO4 Inorganic materials 0.000 claims description 2
• 208000037062 Polyps Diseases 0.000 claims description 2
• 125000003342 alkenyl group Chemical group 0.000 claims description 2
• 125000005189 alkyl hydroxy group Chemical group 0.000 claims description 2
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 2
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 2
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
• 230000002401 inhibitory effect Effects 0.000 claims description 2
• 230000005764 inhibitory process Effects 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
• 239000010452 phosphate Substances 0.000 claims description 2
• 239000000651 prodrug Substances 0.000 claims description 2
• 229940002612 prodrug Drugs 0.000 claims description 2
• 125000006085 pyrrolopyridyl group Chemical group 0.000 claims description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
• 150000003839 salts Chemical class 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
• 0 C*(C)c(c(O)ccc1F)c1F Chemical compound C*(C)c(c(O)ccc1F)c1F 0.000 description 5
• 238000000034 method Methods 0.000 description 5
• HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
• 125000006728 (C1-C6) alkynyl group Chemical group 0.000 description 1
• NAEOBFSYVZULLT-MSOLQXFVSA-N CC(C)N(C1)CC1c1nc(N(C[C@H]2C)[C@@H](C)CN2C(C=C)=O)c(cc(c(-c2c3c(N)n[nH]c3ccc2C)c2F)Cl)c2n1 Chemical compound CC(C)N(C1)CC1c1nc(N(C[C@H]2C)[C@@H](C)CN2C(C=C)=O)c(cc(c(-c2c3c(N)n[nH]c3ccc2C)c2F)Cl)c2n1 NAEOBFSYVZULLT-MSOLQXFVSA-N 0.000 description 1
• OKIRBHVFJGXOIS-UHFFFAOYSA-N CC(C)c1ccccc1C(C)C Chemical compound CC(C)c1ccccc1C(C)C OKIRBHVFJGXOIS-UHFFFAOYSA-N 0.000 description 1
• NNZRVXTXKISCGS-UHFFFAOYSA-N CC(C)c1ccccc1OC Chemical compound CC(C)c1ccccc1OC NNZRVXTXKISCGS-UHFFFAOYSA-N 0.000 description 1
• DOUDTAONKGIZCK-UHFFFAOYSA-N CCc(c(OCc([n]1C)cnc1[N+]([O-])=O)ccc1)c1F Chemical compound CCc(c(OCc([n]1C)cnc1[N+]([O-])=O)ccc1)c1F DOUDTAONKGIZCK-UHFFFAOYSA-N 0.000 description 1
• RVJLLXSRUUFRMM-USSUWNHCSA-N C[C@H](CN([C@@H](C)C1)c2c(cc(c(-c(c(F)cc(C(C3)N3C(C3)CN3c(nc(c3cc(Cl)c4-c(c(F)ccc5)c5O)N(C[C@H]5C)[C@@H](C)CN5C(C=C)=O)nc3c4F)c3)c3O)c3F)Cl)c3nc(C(C3)CN3C3CC3)n2)N1C(C=C)=O Chemical compound C[C@H](CN([C@@H](C)C1)c2c(cc(c(-c(c(F)cc(C(C3)N3C(C3)CN3c(nc(c3cc(Cl)c4-c(c(F)ccc5)c5O)N(C[C@H]5C)[C@@H](C)CN5C(C=C)=O)nc3c4F)c3)c3O)c3F)Cl)c3nc(C(C3)CN3C3CC3)n2)N1C(C=C)=O RVJLLXSRUUFRMM-USSUWNHCSA-N 0.000 description 1
• RNMGRDSONAGDOR-OLZOCXBDSA-N C[C@H](CN([C@@H](C)C1)c2c(cc(c(-c(c(O)ccc3)c3F)c3F)Cl)c3nc(S(C)(=O)=O)n2)N1C(C=C)=O Chemical compound C[C@H](CN([C@@H](C)C1)c2c(cc(c(-c(c(O)ccc3)c3F)c3F)Cl)c3nc(S(C)(=O)=O)n2)N1C(C=C)=O RNMGRDSONAGDOR-OLZOCXBDSA-N 0.000 description 1
• MZLSNIREOQCDED-UHFFFAOYSA-N Cc(c(F)ccc1)c1F Chemical compound Cc(c(F)ccc1)c1F MZLSNIREOQCDED-UHFFFAOYSA-N 0.000 description 1
• VSXYZRINFFKETD-UHFFFAOYSA-N Cc(c(F)ccc1)c1OP(O)(O)=O Chemical compound Cc(c(F)ccc1)c1OP(O)(O)=O VSXYZRINFFKETD-UHFFFAOYSA-N 0.000 description 1
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 1
• 208000015768 polyposis Diseases 0.000 description 1