JP2020519589A5 - - Google Patents

Info

Publication number

JP2020519589A5

JP2020519589A5 JP2019561278A JP2019561278A JP2020519589A5 JP 2020519589 A5 JP2020519589 A5 JP 2020519589A5 JP 2019561278 A JP2019561278 A JP 2019561278A JP 2019561278 A JP2019561278 A JP 2019561278A JP 2020519589 A5 JP2020519589 A5 JP 2020519589A5

Authority

JP

Japan

Prior art keywords

chloro

quinazoline

oxazepino

tetrahydropyrazino

prop

Prior art date

2018-05-08

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.)

Withdrawn

Links

• Espacenet
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• 125000000217 alkyl group Chemical group 0.000 claims description 79
• -1 cyano, acetylenyl Chemical group 0.000 claims description 70
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 56
• HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 claims description 53
• 125000003545 alkoxy group Chemical group 0.000 claims description 48
• 125000000623 heterocyclic group Chemical group 0.000 claims description 46
• 125000001072 heteroaryl group Chemical group 0.000 claims description 38
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 34
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 28
• 150000001875 compounds Chemical class 0.000 claims description 26
• 150000003839 salts Chemical class 0.000 claims description 25
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 8
• 206010028980 Neoplasm Diseases 0.000 claims description 6
• 201000011510 cancer Diseases 0.000 claims description 6
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
• 229910052757 nitrogen Inorganic materials 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 102100030708 GTPase KRas Human genes 0.000 claims description 3
• 102100039788 GTPase NRas Human genes 0.000 claims description 3
• 101000584612 Homo sapiens GTPase KRas Proteins 0.000 claims description 3
• 101000744505 Homo sapiens GTPase NRas Proteins 0.000 claims description 3
• 230000001404 mediated effect Effects 0.000 claims description 3
• 102200006614 rs104894229 Human genes 0.000 claims description 3
• 206010009944 Colon cancer Diseases 0.000 claims description 2
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
• 239000000654 additive Substances 0.000 claims description 2
• 230000000996 additive effect Effects 0.000 claims description 2
• 239000002246 antineoplastic agent Substances 0.000 claims description 2
• 125000003118 aryl group Chemical group 0.000 claims description 2
• 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 2
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 29
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 3
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 1
• OGEKFRWYCZEDFQ-KRWDZBQOSA-N 2-[3-[(7S)-11-chloro-5-prop-2-enoyl-9-oxa-2,5,15,17-tetrazatetracyclo[8.7.1.02,7.014,18]octadeca-1(17),10,12,14(18),15-pentaen-12-yl]phenyl]acetonitrile Chemical compound C(C=C)(=O)N1C[C@H]2COC=3C4=C(N=CN=C4C=C(C=3Cl)C=3C=C(C=CC=3)CC#N)N2CC1 OGEKFRWYCZEDFQ-KRWDZBQOSA-N 0.000 claims 1
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims 1
• DCKOPAMZSONODS-KRWDZBQOSA-N N-[3-[(7S)-11-chloro-5-prop-2-enoyl-9-oxa-2,5,15,17-tetrazatetracyclo[8.7.1.02,7.014,18]octadeca-1(17),10,12,14(18),15-pentaen-12-yl]phenyl]acetamide Chemical compound C(C=C)(=O)N1C[C@H]2COC=3C4=C(N=CN=C4C=C(C=3Cl)C=3C=C(C=CC=3)NC(C)=O)N2CC1 DCKOPAMZSONODS-KRWDZBQOSA-N 0.000 claims 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 1
• GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 claims 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
• 125000005843 halogen group Chemical group 0.000 description 29
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• LGIBDQRYOFBMTC-UHFFFAOYSA-N dnc010031 Chemical compound C1=CC(O)=CC=C1C1C(=O)NC2=CC=CC=C2C2=C3C1=CNC3=NC=C2 LGIBDQRYOFBMTC-UHFFFAOYSA-N 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 3
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
• 208000035475 disorder Diseases 0.000 description 2
• 238000000034 method Methods 0.000 description 2
• 239000000203 mixture Substances 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
• HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1