RU2768746C2 - Замещенные пиразолоазепин-4-оны и их применение в качестве ингибиторов фосфодиэстеразы - Google Patents

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Publication number

RU2768746C2

RU2768746C2 RU2019121694A RU2019121694A RU2768746C2 RU 2768746 C2 RU2768746 C2 RU 2768746C2 RU 2019121694 A RU2019121694 A RU 2019121694A RU 2019121694 A RU2019121694 A RU 2019121694A RU 2768746 C2 RU2768746 C2 RU 2768746C2

Authority

RU

Russia

Prior art keywords

ethyl

tetrahydropyran

spiro

oxo

dihydro

Prior art date

2016-12-12

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• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title 1
• 239000002571 phosphodiesterase inhibitor Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 227
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 120
• 239000001257 hydrogen Substances 0.000 claims abstract description 79
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 79
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 61
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 57
• 125000001424 substituent group Chemical group 0.000 claims abstract description 31
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 29
• 201000004624 Dermatitis Diseases 0.000 claims abstract description 26
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 26
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 23
• 150000003839 salts Chemical class 0.000 claims abstract description 23
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 23
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 18
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 14
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims abstract description 12
• 239000003814 drug Substances 0.000 claims abstract description 11
• MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 claims abstract 12
• 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims abstract 12
• 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims abstract 12
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims abstract 2
• -1 -C(O )R a Chemical group 0.000 claims description 76
• 238000000034 method Methods 0.000 claims description 56
• 150000002431 hydrogen Chemical class 0.000 claims description 50
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 38
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• 125000000217 alkyl group Chemical group 0.000 claims description 26
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• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 15
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• 208000017520 skin disease Diseases 0.000 claims description 12
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• 238000002360 preparation method Methods 0.000 claims description 10
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• UXSOKESSHHZJHP-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2-methyl-1H-imidazole-5-carboxylate Chemical compound CC=1NC=C(N=1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC UXSOKESSHHZJHP-UHFFFAOYSA-N 0.000 claims description 8
• KWUBQECAUIFBFG-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 5-methyl-1H-pyrazole-3-carboxylate Chemical compound CC1=CC(=NN1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC KWUBQECAUIFBFG-UHFFFAOYSA-N 0.000 claims description 8
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• HAFYWFXDIPSNAI-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 2-(2-methyl-1,3-thiazol-4-yl)acetate Chemical compound CC=1SC=C(N=1)CC(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC HAFYWFXDIPSNAI-UHFFFAOYSA-N 0.000 claims description 4
• UOXZSSYZCNPRQP-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 2-(3-methyl-1,2-oxazol-5-yl)acetate Chemical compound CC1=NOC(=C1)CC(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC UOXZSSYZCNPRQP-UHFFFAOYSA-N 0.000 claims description 4
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• PYPYAXBESSTFLX-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 2-methyl-1,3-oxazole-5-carboxylate Chemical compound CC=1OC(=CN=1)C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC PYPYAXBESSTFLX-UHFFFAOYSA-N 0.000 claims description 4
• OBAYZZITEFPYPZ-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 3-methyl-1,2-thiazole-5-carboxylate Chemical compound CC1=NSC(=C1)C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC OBAYZZITEFPYPZ-UHFFFAOYSA-N 0.000 claims description 4
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• QANXFLFJEAXRPX-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1,1-dioxothiane-3-carboxylate Chemical compound O=S1(CC(CCC1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)=O QANXFLFJEAXRPX-UHFFFAOYSA-N 0.000 claims description 4
• MIGYLQMFNCAQDT-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1,1-dioxothiane-4-carboxylate Chemical compound O=S1(CCC(CC1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)=O MIGYLQMFNCAQDT-UHFFFAOYSA-N 0.000 claims description 4
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• IWSMCOFLPKNIAH-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1,3-oxazole-4-carboxylate Chemical compound O1C=NC(=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC IWSMCOFLPKNIAH-UHFFFAOYSA-N 0.000 claims description 4
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• WFPCTDJLSMZGGA-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1,3-thiazole-5-carboxylate Chemical compound S1C=NC=C1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC WFPCTDJLSMZGGA-UHFFFAOYSA-N 0.000 claims description 4
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• TWXKAGXNILXGJY-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1-(dimethylcarbamoyl)piperidine-3-carboxylate Chemical compound CCc1nn(CCCOC(=O)C2CCCN(C2)C(=O)N(C)C)c2CC3(CCOCC3)CNC(=O)c12 TWXKAGXNILXGJY-UHFFFAOYSA-N 0.000 claims description 4
• SQCOPOIHOYNUJY-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1-(dimethylcarbamoyl)piperidine-4-carboxylate Chemical compound CCc1nn(CCCOC(=O)C2CCN(CC2)C(=O)N(C)C)c2CC3(CCOCC3)CNC(=O)c12 SQCOPOIHOYNUJY-UHFFFAOYSA-N 0.000 claims description 4
• OIVFRUXAFOHFCP-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1-acetylazetidine-3-carboxylate Chemical compound C(C)(=O)N1CC(C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC OIVFRUXAFOHFCP-UHFFFAOYSA-N 0.000 claims description 4
• WPSJFVDKOUXGGM-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1-acetylpiperidine-3-carboxylate Chemical compound C(C)(=O)N1CC(CCC1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC WPSJFVDKOUXGGM-UHFFFAOYSA-N 0.000 claims description 4
• JKGQMAHXVYDCDK-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1-acetylpiperidine-4-carboxylate Chemical compound C(C)(=O)N1CCC(CC1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC JKGQMAHXVYDCDK-UHFFFAOYSA-N 0.000 claims description 4
• LILANBHABJCJDM-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1-acetylpyrrolidine-3-carboxylate Chemical compound C(C)(=O)N1CC(CC1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC LILANBHABJCJDM-UHFFFAOYSA-N 0.000 claims description 4
• YYHCDUOZJXULQN-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1-methylimidazole-2-carboxylate Chemical compound CN1C(=NC=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC YYHCDUOZJXULQN-UHFFFAOYSA-N 0.000 claims description 4
• FZPPLOBRJXGLNB-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1-methylimidazole-4-carboxylate Chemical compound CN1C=NC(=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC FZPPLOBRJXGLNB-UHFFFAOYSA-N 0.000 claims description 4
• YZWFYPDTLLESNJ-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1-methylpyrazole-3-carboxylate Chemical compound CN1N=C(C=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC YZWFYPDTLLESNJ-UHFFFAOYSA-N 0.000 claims description 4
• RHTBIHGJMCYJNP-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1-methylpyrazole-4-carboxylate Chemical compound CN1N=CC(=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC RHTBIHGJMCYJNP-UHFFFAOYSA-N 0.000 claims description 4
• NARHXAWCEACFPY-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2,3-dimethylimidazole-4-carboxylate Chemical compound CC1=NC=C(N1C)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC NARHXAWCEACFPY-UHFFFAOYSA-N 0.000 claims description 4
• QDDKVVBATNFZRJ-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2,4-dimethyl-1,3-thiazole-5-carboxylate Chemical compound CC=1SC(=C(N=1)C)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC QDDKVVBATNFZRJ-UHFFFAOYSA-N 0.000 claims description 4
• KMWREPBJATZWDJ-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2,5-dimethyl-1,3-oxazole-4-carboxylate Chemical compound CC=1OC(=C(N=1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)C KMWREPBJATZWDJ-UHFFFAOYSA-N 0.000 claims description 4
• QWFXHIQULDSOQV-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2,5-dimethylpyrazole-3-carboxylate Chemical compound CN1N=C(C=C1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)C QWFXHIQULDSOQV-UHFFFAOYSA-N 0.000 claims description 4
• YIESAWDGBOZTCI-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2,6-dimethylpyridine-3-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2ccc(C)nc2C)c2CC3(CCOCC3)CNC(=O)c12 YIESAWDGBOZTCI-UHFFFAOYSA-N 0.000 claims description 4
• HCUCVODORUZRTH-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2,6-dimethylpyridine-4-carboxylate Chemical compound CC1=NC(=CC(=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)C HCUCVODORUZRTH-UHFFFAOYSA-N 0.000 claims description 4
• ODQWPLPFEVWBEA-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2-cyclopropyl-1,3-oxazole-4-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2coc(n2)C2CC2)c2CC3(CCOCC3)CNC(=O)c12 ODQWPLPFEVWBEA-UHFFFAOYSA-N 0.000 claims description 4
• GUTRKMRKTMVITO-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2-methyl-1,3-oxazole-4-carboxylate Chemical compound CC=1OC=C(N=1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC GUTRKMRKTMVITO-UHFFFAOYSA-N 0.000 claims description 4
• IYVQXADDDXMFPP-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2-methyl-1,3-oxazole-5-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2cnc(C)o2)c2CC3(CCOCC3)CNC(=O)c12 IYVQXADDDXMFPP-UHFFFAOYSA-N 0.000 claims description 4
• PMTSBPQKSLGTOH-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2-methyl-1,3-thiazole-5-carboxylate Chemical compound CC=1SC(=CN=1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC PMTSBPQKSLGTOH-UHFFFAOYSA-N 0.000 claims description 4
• IJQDHFXPLWVPRN-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2-methylpyrazole-3-carboxylate Chemical compound CN1N=CC=C1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC IJQDHFXPLWVPRN-UHFFFAOYSA-N 0.000 claims description 4
• KWNXDZQIEKQSQU-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2-methylpyridine-3-carboxylate Chemical compound CC1=NC=CC=C1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC KWNXDZQIEKQSQU-UHFFFAOYSA-N 0.000 claims description 4
• VUFSTFKHFUFULZ-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2-methylpyrimidine-4-carboxylate Chemical compound CC1=NC=CC(=N1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC VUFSTFKHFUFULZ-UHFFFAOYSA-N 0.000 claims description 4
• RERWWLQMOHADPK-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 2-methylpyrimidine-5-carboxylate Chemical compound CC1=NC=C(C=N1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC RERWWLQMOHADPK-UHFFFAOYSA-N 0.000 claims description 4
• MIOVOVSQKNAUOP-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3,5-diethyl-1,2-oxazole-4-carboxylate Chemical compound C(C)C1=NOC(=C1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)CC MIOVOVSQKNAUOP-UHFFFAOYSA-N 0.000 claims description 4
• QGRXQXKCOMAFPK-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3,5-dimethyl-1,2-oxazole-4-carboxylate Chemical compound CC1=NOC(=C1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)C QGRXQXKCOMAFPK-UHFFFAOYSA-N 0.000 claims description 4
• OALPDDROGONQKX-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3,6-dimethylpyridazine-4-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2cc(C)nnc2C)c2CC3(CCOCC3)CNC(=O)c12 OALPDDROGONQKX-UHFFFAOYSA-N 0.000 claims description 4
• QHIIAHVEFAJYFO-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3-methyl-1,2-oxazole-4-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2conc2C)c2CC3(CCOCC3)CNC(=O)c12 QHIIAHVEFAJYFO-UHFFFAOYSA-N 0.000 claims description 4
• UATLQUMLKQXMNN-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3-methyl-1,2-oxazole-5-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2cc(C)no2)c2CC3(CCOCC3)CNC(=O)c12 UATLQUMLKQXMNN-UHFFFAOYSA-N 0.000 claims description 4
• UBRJCTAORZUAFI-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3-methyl-1,2-thiazole-5-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2cc(C)ns2)c2CC3(CCOCC3)CNC(=O)c12 UBRJCTAORZUAFI-UHFFFAOYSA-N 0.000 claims description 4
• WKVDLPKHLOUXSY-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3-methylbenzimidazole-5-carboxylate Chemical compound CN1C=NC2=C1C=C(C=C2)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC WKVDLPKHLOUXSY-UHFFFAOYSA-N 0.000 claims description 4
• UFULYYVTMROKDV-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3-methylimidazole-4-carboxylate Chemical compound CN1C=NC=C1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC UFULYYVTMROKDV-UHFFFAOYSA-N 0.000 claims description 4
• WQWUOWZGTOODFX-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3-methylpyridazine-4-carboxylate Chemical compound CC=1N=NC=CC=1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC WQWUOWZGTOODFX-UHFFFAOYSA-N 0.000 claims description 4
• RPCPTIHBDDHRJB-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3-methylpyridine-2-carboxylate Chemical compound CC=1C(=NC=CC=1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC RPCPTIHBDDHRJB-UHFFFAOYSA-N 0.000 claims description 4
• RFHPKWKGSOKPDR-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3-methyltriazole-4-carboxylate Chemical compound CN1N=NC=C1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC RFHPKWKGSOKPDR-UHFFFAOYSA-N 0.000 claims description 4
• MXZAYZTWSIPGMH-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 3-oxo-1,2-oxazole-5-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2cc(=O)[nH]o2)c2CC3(CCOCC3)CNC(=O)c12 MXZAYZTWSIPGMH-UHFFFAOYSA-N 0.000 claims description 4
• YHGWKFPGUAXVHO-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 4,5-dimethyl-1,2-oxazole-3-carboxylate Chemical compound CC=1C(=NOC=1C)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC YHGWKFPGUAXVHO-UHFFFAOYSA-N 0.000 claims description 4
• ROVPIDGXVWOFFV-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 4,5-dimethyl-1,3-thiazole-2-carboxylate Chemical compound CC=1N=C(SC=1C)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC ROVPIDGXVWOFFV-UHFFFAOYSA-N 0.000 claims description 4
• LVUWFBAGACNFNP-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 4-methyl-1,2,5-oxadiazole-3-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2nonc2C)c2CC3(CCOCC3)CNC(=O)c12 LVUWFBAGACNFNP-UHFFFAOYSA-N 0.000 claims description 4
• JBHUFWUEKXBWMN-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 4-methyl-1,2-oxazole-5-carboxylate Chemical compound CC=1C=NOC=1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC JBHUFWUEKXBWMN-UHFFFAOYSA-N 0.000 claims description 4
• FCEDSDSGVAMMID-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 4-methyl-1,3-oxazole-5-carboxylate Chemical compound CC=1N=COC=1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC FCEDSDSGVAMMID-UHFFFAOYSA-N 0.000 claims description 4
• JAEZLLNINLLBHY-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 4-methyl-1,3-thiazole-5-carboxylate Chemical compound CC=1N=CSC=1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC JAEZLLNINLLBHY-UHFFFAOYSA-N 0.000 claims description 4
• ULNGFIWJVXYBSY-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 4-methylpyridine-2-carboxylate Chemical compound CC1=CC(=NC=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC ULNGFIWJVXYBSY-UHFFFAOYSA-N 0.000 claims description 4
• GMKASWYKSDFOSS-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 4-methylpyrimidine-2-carboxylate Chemical compound CC1=NC(=NC=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC GMKASWYKSDFOSS-UHFFFAOYSA-N 0.000 claims description 4
• FKVAGTRWLDNBBK-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 4-methylthiadiazole-5-carboxylate Chemical compound CC=1N=NSC=1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC FKVAGTRWLDNBBK-UHFFFAOYSA-N 0.000 claims description 4
• YHNVFWMLRWMTSR-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 5-methyl-1,2-oxazole-3-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2cc(C)on2)c2CC3(CCOCC3)CNC(=O)c12 YHNVFWMLRWMTSR-UHFFFAOYSA-N 0.000 claims description 4
• NJLWOJWIEFWMAN-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 5-methyl-1,2-thiazole-4-carboxylate Chemical compound CC1=C(C=NS1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC NJLWOJWIEFWMAN-UHFFFAOYSA-N 0.000 claims description 4
• QLJCDKGHNSVOSE-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 5-methyl-1,3-thiazole-4-carboxylate Chemical compound CC1=C(N=CS1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC QLJCDKGHNSVOSE-UHFFFAOYSA-N 0.000 claims description 4
• ZBEYGAGZAAWOPS-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 5-methyl-1H-1,2,4-triazole-3-carboxylate Chemical compound CC=1NC(=NN=1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC ZBEYGAGZAAWOPS-UHFFFAOYSA-N 0.000 claims description 4
• LTPAIEVGNIBLGI-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 5-methylpyridine-2-carboxylate Chemical compound CC=1C=CC(=NC=1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC LTPAIEVGNIBLGI-UHFFFAOYSA-N 0.000 claims description 4
• VEIBTFDTQJCIRQ-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 5-methylpyrimidine-2-carboxylate Chemical compound CC=1C=NC(=NC=1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC VEIBTFDTQJCIRQ-UHFFFAOYSA-N 0.000 claims description 4
• PCIBMZMKFSKDKI-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 6-methylpyridine-2-carboxylate Chemical compound CC1=CC=CC(=N1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC PCIBMZMKFSKDKI-UHFFFAOYSA-N 0.000 claims description 4
• GJJKQFKHCMQSFX-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl oxane-3-carboxylate Chemical compound O1CC(CCC1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC GJJKQFKHCMQSFX-UHFFFAOYSA-N 0.000 claims description 4
• KGGNVNJCSHVGDQ-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl oxane-4-carboxylate Chemical compound O1CCC(CC1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC KGGNVNJCSHVGDQ-UHFFFAOYSA-N 0.000 claims description 4
• HUWVJSLWNGBTIP-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl oxolane-3-carboxylate Chemical compound O1CC(CC1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC HUWVJSLWNGBTIP-UHFFFAOYSA-N 0.000 claims description 4
• VGGGCWREMDPVBL-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl pyridazine-3-carboxylate Chemical compound N1=NC(=CC=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC VGGGCWREMDPVBL-UHFFFAOYSA-N 0.000 claims description 4
• CFSOGXWWEQPORW-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl pyridazine-4-carboxylate Chemical compound N1=NC=C(C=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC CFSOGXWWEQPORW-UHFFFAOYSA-N 0.000 claims description 4
• PUAGWTSYYUPQNF-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl pyrimidine-2-carboxylate Chemical compound N1=C(N=CC=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC PUAGWTSYYUPQNF-UHFFFAOYSA-N 0.000 claims description 4
• ILDYCAOSQXVNDI-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl thiadiazole-4-carboxylate Chemical compound S1N=NC(=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC ILDYCAOSQXVNDI-UHFFFAOYSA-N 0.000 claims description 4
• VFGPHVHXWWTNFF-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl thiane-3-carboxylate Chemical compound CCc1nn(CCCOC(=O)C2CCCSC2)c2CC3(CCOCC3)CNC(=O)c12 VFGPHVHXWWTNFF-UHFFFAOYSA-N 0.000 claims description 4
• DJLDWOKHKKPAAR-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl thiane-4-carboxylate Chemical compound CCc1nn(CCCOC(=O)C2CCSCC2)c2CC3(CCOCC3)CNC(=O)c12 DJLDWOKHKKPAAR-UHFFFAOYSA-N 0.000 claims description 4
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