JP2020520925A5 - - Google Patents
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- JP2020520925A5 JP2020520925A5 JP2019563609A JP2019563609A JP2020520925A5 JP 2020520925 A5 JP2020520925 A5 JP 2020520925A5 JP 2019563609 A JP2019563609 A JP 2019563609A JP 2019563609 A JP2019563609 A JP 2019563609A JP 2020520925 A5 JP2020520925 A5 JP 2020520925A5
- Authority
- JP
- Japan
- Prior art keywords
- optionally substituted
- diazepine
- compound according
- hexahydropyrazolo
- heterocyclyl
- Prior art date
- 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
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- LAODNOQGDMJAOS-UHFFFAOYSA-N 5-(6,6-dimethyl-5-oxo-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-3-yl)pyridine-3-carbonitrile Chemical compound CC1(C)CCCN2CCC(N2C1=O)c1cncc(c1)C#N LAODNOQGDMJAOS-UHFFFAOYSA-N 0.000 claims description 3
- QSPGMCGSCMXMNL-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-6,6-dimethyl-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-5-one Chemical compound CC1(C)CCCN2CCC(N2C1=O)c1ccc(F)c(F)c1 QSPGMCGSCMXMNL-UHFFFAOYSA-N 0.000 claims description 2
- STCDRGVTQJNRGW-UHFFFAOYSA-N 3-(3,5-difluorophenyl)-6,6-dimethyl-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-5-one Chemical compound CC1(C)CCCN2CCC(N2C1=O)c1cc(F)cc(F)c1 STCDRGVTQJNRGW-UHFFFAOYSA-N 0.000 claims description 2
- QVEMDBXTQXHHAB-UHFFFAOYSA-N 3-(3-fluorophenyl)-6,6-dimethyl-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-5-one Chemical compound CC1(C)CCCN2CCC(N2C1=O)c1cccc(F)c1 QVEMDBXTQXHHAB-UHFFFAOYSA-N 0.000 claims description 2
- AGCGZWOZRAZHMZ-UHFFFAOYSA-N 3-(5-fluoropyridin-3-yl)-6,6-dimethyl-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-5-one Chemical compound CC1(C)CCCN2CCC(N2C1=O)c1cncc(F)c1 AGCGZWOZRAZHMZ-UHFFFAOYSA-N 0.000 claims description 2
- TTWMEHAWZMMXLK-UHFFFAOYSA-N 3-(5-fluoropyridin-3-yl)spiro[1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepine-6,1'-cyclopropane]-5-one Chemical compound FC1=CC(C2N3N(CC2)CCCC2(C3=O)CC2)=CN=C1 TTWMEHAWZMMXLK-UHFFFAOYSA-N 0.000 claims description 2
- MOFBCWRMOAILLK-UHFFFAOYSA-N 3-(6,6-dimethyl-5-oxo-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-3-yl)-5-fluorobenzonitrile Chemical compound CC1(C)CCCN2CCC(N2C1=O)c1cc(F)cc(c1)C#N MOFBCWRMOAILLK-UHFFFAOYSA-N 0.000 claims description 2
- NYPLMFCBARDUKW-UHFFFAOYSA-N 4-(6,6-dimethyl-5-oxo-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-3-yl)benzonitrile Chemical compound CC1(C)CCCN2CCC(N2C1=O)c1ccc(cc1)C#N NYPLMFCBARDUKW-UHFFFAOYSA-N 0.000 claims description 2
- UCYWTJSYPAWQBD-UHFFFAOYSA-N 5-[6-(difluoromethyl)-6-methyl-5-oxo-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-3-yl]pyridine-3-carbonitrile Chemical compound CC1(CCCN2CCC(N2C1=O)c1cncc(c1)C#N)C(F)F UCYWTJSYPAWQBD-UHFFFAOYSA-N 0.000 claims description 2
- WSAHDARCBJLIGV-UHFFFAOYSA-N 6,6-dimethyl-3-(5-methylpyrazin-2-yl)-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-5-one Chemical compound Cc1cnc(cn1)C1CCN2CCCC(C)(C)C(=O)N12 WSAHDARCBJLIGV-UHFFFAOYSA-N 0.000 claims description 2
- WTNUKYCIXBOCNF-UHFFFAOYSA-N 6-(difluoromethyl)-3-(5-fluoropyridin-3-yl)-6-methyl-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-5-one Chemical compound CC1(CCCN2CCC(N2C1=O)c1cncc(F)c1)C(F)F WTNUKYCIXBOCNF-UHFFFAOYSA-N 0.000 claims description 2
- PHTCEKYUIRGSET-UHFFFAOYSA-N 6-(difluoromethyl)-6-methyl-3-(5-methylpyrazin-2-yl)-1,2,3,7,8,9-hexahydropyrazolo[1,2-a]diazepin-5-one Chemical compound Cc1cnc(cn1)C1CCN2CCCC(C)(C(F)F)C(=O)N12 PHTCEKYUIRGSET-UHFFFAOYSA-N 0.000 claims description 2
- SFFOQVMDVZWHBQ-UHFFFAOYSA-N 7,7-difluoro-3-(5-fluoropyridin-3-yl)-6,6-dimethyl-2,3,8,9-tetrahydro-1H-pyrazolo[1,2-a]diazepin-5-one Chemical compound C1=C(C=C(C=N1)C1N2N(CC1)CCC(C(C2=O)(C)C)(F)F)F SFFOQVMDVZWHBQ-UHFFFAOYSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 20
- -1 5-cyano-pyrid-3-yl Chemical group 0.000 claims 12
- 125000000623 heterocyclic group Chemical group 0.000 claims 12
- 125000005843 halogen group Chemical group 0.000 claims 10
- 125000001072 heteroaryl group Chemical group 0.000 claims 7
- 125000000547 substituted alkyl group Chemical group 0.000 claims 7
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 6
- 125000000217 alkyl group Chemical group 0.000 claims 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 5
- 239000000651 prodrug Substances 0.000 claims 5
- 229940002612 prodrug Drugs 0.000 claims 5
- 150000003839 salts Chemical class 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 125000003107 substituted aryl group Chemical group 0.000 claims 4
- 125000003118 aryl group Chemical group 0.000 claims 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
- 125000005017 substituted alkenyl group Chemical group 0.000 claims 3
- 125000004426 substituted alkynyl group Chemical group 0.000 claims 3
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 230000004770 neurodegeneration Effects 0.000 claims 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims 2
- NBJDSMIOWPVWRW-UHFFFAOYSA-N 2h-oxazepin-5-one Chemical compound O=C1C=CNOC=C1 NBJDSMIOWPVWRW-UHFFFAOYSA-N 0.000 claims 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 101001113278 Arabidopsis thaliana Probable serine/threonine-protein kinase PBL9 Proteins 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims 1
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 1
- 230000010799 Receptor Interactions Effects 0.000 claims 1
- 125000006193 alkinyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 238000006356 dehydrogenation reaction Methods 0.000 claims 1
- ZGLDQGIONSGJCN-UHFFFAOYSA-N diazepin-5-one Chemical compound O=C1C=CN=NC=C1 ZGLDQGIONSGJCN-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 150000003216 pyrazines Chemical class 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
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