ES2981006T3 - Pirazoloazepin-4-onas sustituidas y su uso como inhibidores de la fosfodiesterasa - Google Patents

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Publication number

ES2981006T3

ES2981006T3 ES17811328T ES17811328T ES2981006T3 ES 2981006 T3 ES2981006 T3 ES 2981006T3 ES 17811328 T ES17811328 T ES 17811328T ES 17811328 T ES17811328 T ES 17811328T ES 2981006 T3 ES2981006 T3 ES 2981006T3

Authority

ES

Spain

Prior art keywords

tetrahydropyran

spiro

oxo

dihydro

pyrazolo

Prior art date

2016-12-12

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.)

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• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title description 2
• 239000002571 phosphodiesterase inhibitor Substances 0.000 title description 2
• 238000011282 treatment Methods 0.000 claims abstract description 36
• 239000003814 drug Substances 0.000 claims abstract description 11
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 9
• 150000001875 compounds Chemical class 0.000 claims description 228
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 140
• 239000001257 hydrogen Substances 0.000 claims description 80
• 229910052739 hydrogen Inorganic materials 0.000 claims description 80
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 78
• -1 cyano, hydroxyl Chemical group 0.000 claims description 75
• 125000001072 heteroaryl group Chemical group 0.000 claims description 64
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 57
• 150000002431 hydrogen Chemical class 0.000 claims description 46
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
• 125000001424 substituent group Chemical group 0.000 claims description 30
• 125000003545 alkoxy group Chemical group 0.000 claims description 25
• 125000004432 carbon atom Chemical group C* 0.000 claims description 25
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
• 201000010099 disease Diseases 0.000 claims description 24
• 150000003839 salts Chemical class 0.000 claims description 21
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
• 229910003827 NRaRb Inorganic materials 0.000 claims description 19
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 16
• 201000004624 Dermatitis Diseases 0.000 claims description 15
• 208000035475 disorder Diseases 0.000 claims description 15
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
• 239000012453 solvate Substances 0.000 claims description 15
• 125000003118 aryl group Chemical group 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 229910052757 nitrogen Inorganic materials 0.000 claims description 13
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 12
• 206010040799 Skin atrophy Diseases 0.000 claims description 12
• 201000008937 atopic dermatitis Diseases 0.000 claims description 12
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 12
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
• 230000002500 effect on skin Effects 0.000 claims description 11
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
• 229910052701 rubidium Inorganic materials 0.000 claims description 10
• 201000004681 Psoriasis Diseases 0.000 claims description 9
• 229910052799 carbon Inorganic materials 0.000 claims description 9
• 208000002874 Acne Vulgaris Diseases 0.000 claims description 8
• 208000003251 Pruritus Diseases 0.000 claims description 8
• 206010000496 acne Diseases 0.000 claims description 8
• 208000004631 alopecia areata Diseases 0.000 claims description 8
• 208000010668 atopic eczema Diseases 0.000 claims description 8
• 201000004384 Alopecia Diseases 0.000 claims description 7
• 206010012442 Dermatitis contact Diseases 0.000 claims description 7
• 206010061218 Inflammation Diseases 0.000 claims description 7
• 206010028980 Neoplasm Diseases 0.000 claims description 7
• 206010039793 Seborrhoeic dermatitis Diseases 0.000 claims description 7
• 208000024780 Urticaria Diseases 0.000 claims description 7
• 231100000360 alopecia Toxicity 0.000 claims description 7
• 201000011510 cancer Diseases 0.000 claims description 7
• 208000010247 contact dermatitis Diseases 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• 230000004054 inflammatory process Effects 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• 230000002062 proliferating effect Effects 0.000 claims description 7
• 208000008742 seborrheic dermatitis Diseases 0.000 claims description 7
• 150000003431 steroids Chemical class 0.000 claims description 7
• 206010051246 Photodermatosis Diseases 0.000 claims description 6
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 150000004677 hydrates Chemical class 0.000 claims description 6
• 125000003566 oxetanyl group Chemical group 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 230000008845 photoaging Effects 0.000 claims description 6
• 230000009759 skin aging Effects 0.000 claims description 6
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 208000017520 skin disease Diseases 0.000 claims description 4
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 3
• NWFZGBSWGCSHIT-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 1,2-oxazole-5-carboxylate Chemical compound O1N=CC=C1C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC NWFZGBSWGCSHIT-UHFFFAOYSA-N 0.000 claims description 3
• NOIZOESTOOKNLY-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 1,3-oxazole-4-carboxylate Chemical compound O1C=NC(=C1)C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC NOIZOESTOOKNLY-UHFFFAOYSA-N 0.000 claims description 3
• LQDDISDQOYFJBM-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 1,3-thiazole-4-carboxylate Chemical compound S1C=NC(=C1)C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC LQDDISDQOYFJBM-UHFFFAOYSA-N 0.000 claims description 3
• DVLQYAMIPLJJRS-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-4-carboxylate Chemical compound CC=1OC=C(N=1)C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC DVLQYAMIPLJJRS-UHFFFAOYSA-N 0.000 claims description 3
• TYPUQARCHBRKCW-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl oxane-4-carboxylate Chemical compound O1CCC(CC1)C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC TYPUQARCHBRKCW-UHFFFAOYSA-N 0.000 claims description 3
• TYGWCCFOOIFBLI-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1,2-oxazole-3-carboxylate Chemical compound O1N=C(C=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC TYGWCCFOOIFBLI-UHFFFAOYSA-N 0.000 claims description 3
• GQEAVGSPFMLJTQ-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1,2-thiazole-3-carboxylate Chemical compound S1N=C(C=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC GQEAVGSPFMLJTQ-UHFFFAOYSA-N 0.000 claims description 3
• WHYFOKZGKYBOHM-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1,2-thiazole-4-carboxylate Chemical compound S1N=CC(=C1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC WHYFOKZGKYBOHM-UHFFFAOYSA-N 0.000 claims description 3
• FYDORRLXLINYQH-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1,2-thiazole-5-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2ccns2)c2CC3(CCOCC3)CNC(=O)c12 FYDORRLXLINYQH-UHFFFAOYSA-N 0.000 claims description 3
• DICZXRWNQDUQQD-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-5-carboxylate Chemical compound O1C=NC=C1C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC DICZXRWNQDUQQD-UHFFFAOYSA-N 0.000 claims description 3
• 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 3
• 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 3
• 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 3
• 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 3
• 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 3
• 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 3
• 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 3
• XLAVALRZCSWRTB-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl thiolane-3-carboxylate Chemical compound S1CC(CC1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC XLAVALRZCSWRTB-UHFFFAOYSA-N 0.000 claims description 3
• NTIZCSSGYWSNGH-UHFFFAOYSA-N 4-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)butyl 1,2-thiazole-4-carboxylate Chemical compound S1N=CC(=C1)C(=O)OCCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC NTIZCSSGYWSNGH-UHFFFAOYSA-N 0.000 claims description 3
• JSTWVHDZAPBBAJ-UHFFFAOYSA-N 4-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)butyl 1,3-thiazole-4-carboxylate Chemical compound S1C=NC(=C1)C(=O)OCCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC JSTWVHDZAPBBAJ-UHFFFAOYSA-N 0.000 claims description 3
• TZJBLNDNGKRMQY-UHFFFAOYSA-N 4-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)butyl oxane-4-carboxylate Chemical compound O1CCC(CC1)C(=O)OCCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC TZJBLNDNGKRMQY-UHFFFAOYSA-N 0.000 claims description 3
• STAIUSLCGCJRDC-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] oxolane-3-carboxylate Chemical compound O1CC(CC1)C(=O)OCC(CN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)(C)C STAIUSLCGCJRDC-UHFFFAOYSA-N 0.000 claims description 3
• DFOGZDFWEWBHHY-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 1-acetylpiperidine-4-carboxylate Chemical compound C(C)(=O)N1CCC(CC1)C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC DFOGZDFWEWBHHY-UHFFFAOYSA-N 0.000 claims description 2
• BQJXSRQJKDJVOJ-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 1-methylpyrazole-4-carboxylate Chemical compound CN1N=CC(=C1)C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC BQJXSRQJKDJVOJ-UHFFFAOYSA-N 0.000 claims description 2
• 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 2
• 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 2
• OVUURAFHWUEEJZ-UHFFFAOYSA-N 4-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)butyl 2-methyl-1,3-oxazole-5-carboxylate Chemical compound CC=1OC(=CN=1)C(=O)OCCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC OVUURAFHWUEEJZ-UHFFFAOYSA-N 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
• BJLXLCDEKNCPGH-UHFFFAOYSA-N propyl pyrimidine-2-carboxylate Chemical compound CCCOC(=O)C1=NC=CC=N1 BJLXLCDEKNCPGH-UHFFFAOYSA-N 0.000 claims description 2
• 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 2
• 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 2
• JUWHQANQIXFDDM-UHFFFAOYSA-N 1-methoxycarbonylpiperidine-3-carboxylic acid Chemical compound COC(=O)N1CCCC(C(O)=O)C1 JUWHQANQIXFDDM-UHFFFAOYSA-N 0.000 claims 1
• FDQGMCHKKYRKCB-UHFFFAOYSA-N 1-methoxycarbonylpiperidine-4-carboxylic acid Chemical compound COC(=O)N1CCC(C(O)=O)CC1 FDQGMCHKKYRKCB-UHFFFAOYSA-N 0.000 claims 1
• QIAPYZPWWDYUTL-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 1,5-dimethylpyrazole-3-carboxylate Chemical compound CCc1nn(CCOC(=O)c2cc(C)n(C)n2)c2CC3(CCOCC3)CNC(=O)c12 QIAPYZPWWDYUTL-UHFFFAOYSA-N 0.000 claims 1
• PYHNYNHTVIPQMB-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 2-(1-methylpyrrol-2-yl)acetate Chemical compound CN1C(=CC=C1)CC(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC PYHNYNHTVIPQMB-UHFFFAOYSA-N 0.000 claims 1
• 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 1
• 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 1
• FEDHJXJOSCFUGU-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 2-(5-methyl-1,2-oxazol-3-yl)acetate Chemical compound CC1=CC(=NO1)CC(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC FEDHJXJOSCFUGU-UHFFFAOYSA-N 0.000 claims 1
• 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 1
• RCUVTUFNLZLPIS-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 4-methyl-1,3-thiazole-2-carboxylate Chemical compound CC=1N=C(SC=1)C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC RCUVTUFNLZLPIS-UHFFFAOYSA-N 0.000 claims 1
• ZPVLOTHXPAUVOP-UHFFFAOYSA-N 2-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)ethyl 5-methyl-1,2-oxazole-3-carboxylate Chemical compound CC1=CC(=NO1)C(=O)OCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC ZPVLOTHXPAUVOP-UHFFFAOYSA-N 0.000 claims 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims 1
• SFYGTYAKDKVZSS-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1,1-dioxothiolane-3-carboxylate Chemical compound O=S1(CC(CC1)C(=O)OCCCN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)=O SFYGTYAKDKVZSS-UHFFFAOYSA-N 0.000 claims 1
• DRJQBDPJMCUJJE-UHFFFAOYSA-N 3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)propyl 1,3,5-trimethylpyrazole-4-carboxylate Chemical compound CCc1nn(CCCOC(=O)c2c(C)nn(C)c2C)c2CC3(CCOCC3)CNC(=O)c12 DRJQBDPJMCUJJE-UHFFFAOYSA-N 0.000 claims 1
• 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 1
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• 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 1
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• 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 1
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• 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 1
• 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 1
• 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 1
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