ES2875128T3 - Pirazoloazepin-8-onas sustituidas y su uso como inhibidores de la fosfodiesterasa - Google Patents
Pirazoloazepin-8-onas sustituidas y su uso como inhibidores de la fosfodiesterasa Download PDFInfo
- Publication number
- ES2875128T3 ES2875128T3 ES16809388T ES16809388T ES2875128T3 ES 2875128 T3 ES2875128 T3 ES 2875128T3 ES 16809388 T ES16809388 T ES 16809388T ES 16809388 T ES16809388 T ES 16809388T ES 2875128 T3 ES2875128 T3 ES 2875128T3
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- Spain
- Prior art keywords
- spiro
- dihydro
- pyrazolo
- oxo
- tetrahydropyran
- Prior art date
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- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title description 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 title description 2
- HOQUEALWVBGCGP-UHFFFAOYSA-N 7H-pyrazolo[4,3-b]azepin-8-one Chemical class N=1N=CC=2C=1C(CC=CN=2)=O HOQUEALWVBGCGP-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 250
- -1 cyano, hydroxyl Chemical group 0.000 claims abstract description 132
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 92
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 74
- 239000001257 hydrogen Substances 0.000 claims abstract description 74
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 56
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 52
- 229910003827 NRaRb Inorganic materials 0.000 claims abstract description 45
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 45
- 125000003118 aryl group Chemical group 0.000 claims abstract description 38
- 125000001424 substituent group Chemical group 0.000 claims abstract description 38
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 34
- 150000002367 halogens Chemical class 0.000 claims abstract description 33
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 23
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 19
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 17
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 17
- 239000012453 solvate Substances 0.000 claims abstract description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 15
- 125000003566 oxetanyl group Chemical group 0.000 claims abstract description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims abstract description 12
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 11
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 10
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 9
- 150000004677 hydrates Chemical class 0.000 claims abstract description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 7
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 6
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract 2
- 238000011282 treatment Methods 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- SCDLFTKTPUXGJS-UHFFFAOYSA-N 3-ethylspiro[1,5,6,8-tetrahydropyrazolo[4,3-c]azepine-7,4'-oxane]-4-one Chemical compound C(C)C1=NNC2=C1C(NCC1(CCOCC1)C2)=O SCDLFTKTPUXGJS-UHFFFAOYSA-N 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 14
- 208000035475 disorder Diseases 0.000 claims description 11
- 201000004624 Dermatitis Diseases 0.000 claims description 10
- 229940095102 methyl benzoate Drugs 0.000 claims description 10
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 9
- 201000008937 atopic dermatitis Diseases 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 206010040799 Skin atrophy Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- FNJPHLBTJIHHPG-UHFFFAOYSA-N 2-(2-cyanophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=CC=C1C#N FNJPHLBTJIHHPG-UHFFFAOYSA-N 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 5
- 208000003251 Pruritus Diseases 0.000 claims description 5
- 206010000496 acne Diseases 0.000 claims description 5
- 208000004631 alopecia areata Diseases 0.000 claims description 5
- 208000010668 atopic eczema Diseases 0.000 claims description 5
- UDEWPOVQBGFNGE-UHFFFAOYSA-N benzoic acid n-propyl ester Natural products CCCOC(=O)C1=CC=CC=C1 UDEWPOVQBGFNGE-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000002500 effect on skin Effects 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 208000017520 skin disease Diseases 0.000 claims description 5
- WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 claims description 4
- 201000004384 Alopecia Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 206010051246 Photodermatosis Diseases 0.000 claims description 4
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 claims description 4
- 208000024780 Urticaria Diseases 0.000 claims description 4
- 231100000360 alopecia Toxicity 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000008845 photoaging Effects 0.000 claims description 4
- 230000002062 proliferating effect Effects 0.000 claims description 4
- 208000008742 seborrheic dermatitis Diseases 0.000 claims description 4
- 230000009759 skin aging Effects 0.000 claims description 4
- 150000003431 steroids Chemical class 0.000 claims description 4
- 206010012442 Dermatitis contact Diseases 0.000 claims description 3
- 208000010247 contact dermatitis Diseases 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 claims description 3
- AJBWNNKDUMXZLM-UHFFFAOYSA-N 4-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=C(C(O)=O)C=C1 AJBWNNKDUMXZLM-UHFFFAOYSA-N 0.000 claims description 2
- 230000007803 itching Effects 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 47
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims 5
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 4
- NSGKIIGVPBTOBF-UHFFFAOYSA-M 3-fluoro-5-(trifluoromethyl)benzoate Chemical compound [O-]C(=O)C1=CC(F)=CC(C(F)(F)F)=C1 NSGKIIGVPBTOBF-UHFFFAOYSA-M 0.000 claims 2
- SWKPKONEIZGROQ-UHFFFAOYSA-M 4-(trifluoromethyl)benzoate Chemical compound [O-]C(=O)C1=CC=C(C(F)(F)F)C=C1 SWKPKONEIZGROQ-UHFFFAOYSA-M 0.000 claims 2
- LTIXOYIZMIXNIK-UHFFFAOYSA-N 4-pyrrolidin-1-ylsulfonylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1S(=O)(=O)N1CCCC1 LTIXOYIZMIXNIK-UHFFFAOYSA-N 0.000 claims 2
- 101100485158 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) wzzE gene Proteins 0.000 claims 2
- XSIFPSYPOVKYCO-UHFFFAOYSA-N benzoic acid butyl ester Natural products CCCCOC(=O)C1=CC=CC=C1 XSIFPSYPOVKYCO-UHFFFAOYSA-N 0.000 claims 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 101150089110 metN gene Proteins 0.000 claims 2
- DUKYPQBGYRJVAN-UHFFFAOYSA-N methyl 3-methoxybenzoate Chemical compound COC(=O)C1=CC=CC(OC)=C1 DUKYPQBGYRJVAN-UHFFFAOYSA-N 0.000 claims 2
- MSEBQGULDWDIRW-UHFFFAOYSA-N methyl 4-fluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1 MSEBQGULDWDIRW-UHFFFAOYSA-N 0.000 claims 2
- LPNBBFKOUUSUDB-UHFFFAOYSA-M p-toluate Chemical compound CC1=CC=C(C([O-])=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-M 0.000 claims 2
- FBRJYBGLCHWYOE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(F)(F)F FBRJYBGLCHWYOE-UHFFFAOYSA-N 0.000 claims 1
- GRPWQLDSGNZEQE-UHFFFAOYSA-N 2-chloro-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1Cl GRPWQLDSGNZEQE-UHFFFAOYSA-N 0.000 claims 1
- MIZKCMSSYVUZKD-UHFFFAOYSA-N 2-chloro-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1Cl MIZKCMSSYVUZKD-UHFFFAOYSA-N 0.000 claims 1
- OCIYTBZXTFPSPI-UHFFFAOYSA-M 2-fluoro-4-(trifluoromethyl)benzoate Chemical compound [O-]C(=O)C1=CC=C(C(F)(F)F)C=C1F OCIYTBZXTFPSPI-UHFFFAOYSA-M 0.000 claims 1
- LIFKXWNFWIUMJT-UHFFFAOYSA-M 2-fluoro-5-(trifluoromethyl)benzoate Chemical compound [O-]C(=O)C1=CC(C(F)(F)F)=CC=C1F LIFKXWNFWIUMJT-UHFFFAOYSA-M 0.000 claims 1
- SOWDWUPMHVDZGL-UHFFFAOYSA-N 2-methoxy-4-methylbenzoic acid Chemical compound COC1=CC(C)=CC=C1C(O)=O SOWDWUPMHVDZGL-UHFFFAOYSA-N 0.000 claims 1
- FQXQBFUUVCDIRK-UHFFFAOYSA-M 3-(trifluoromethyl)benzoate Chemical compound [O-]C(=O)C1=CC=CC(C(F)(F)F)=C1 FQXQBFUUVCDIRK-UHFFFAOYSA-M 0.000 claims 1
- FVUKYCZRWSQGAS-UHFFFAOYSA-N 3-carbamoylbenzoic acid Chemical compound NC(=O)C1=CC=CC(C(O)=O)=C1 FVUKYCZRWSQGAS-UHFFFAOYSA-N 0.000 claims 1
- SDKUOEOJAXGCLU-UHFFFAOYSA-M 3-chloro-4-methylbenzoate Chemical compound CC1=CC=C(C([O-])=O)C=C1Cl SDKUOEOJAXGCLU-UHFFFAOYSA-M 0.000 claims 1
- MXNBDFWNYRNIBH-UHFFFAOYSA-N 3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1 MXNBDFWNYRNIBH-UHFFFAOYSA-N 0.000 claims 1
- CEAVPXDEPGAVDA-UHFFFAOYSA-N 3-methoxy-4-methylbenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1C CEAVPXDEPGAVDA-UHFFFAOYSA-N 0.000 claims 1
- UZMCSTKSVWZMJA-UHFFFAOYSA-N 3-pyrrolidin-1-ylsulfonylbenzoic acid Chemical compound OC(=O)C1=CC=CC(S(=O)(=O)N2CCCC2)=C1 UZMCSTKSVWZMJA-UHFFFAOYSA-N 0.000 claims 1
- AHFINSWGYAZBOZ-UHFFFAOYSA-N 4-chloro-2-(trifluoromethyl)benzaldehyde Chemical group FC(F)(F)C1=CC(Cl)=CC=C1C=O AHFINSWGYAZBOZ-UHFFFAOYSA-N 0.000 claims 1
- ZLPXBWMVZANJJQ-UHFFFAOYSA-M 4-chloro-2-fluorobenzoate Chemical compound [O-]C(=O)C1=CC=C(Cl)C=C1F ZLPXBWMVZANJJQ-UHFFFAOYSA-M 0.000 claims 1
- XXFKOBGFMUIWDH-UHFFFAOYSA-M 4-chloro-2-methylbenzoate Chemical compound CC1=CC(Cl)=CC=C1C([O-])=O XXFKOBGFMUIWDH-UHFFFAOYSA-M 0.000 claims 1
- PPHHAZOVVZBSCM-UHFFFAOYSA-M 4-chloro-3-(trifluoromethyl)benzoate Chemical compound [O-]C(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 PPHHAZOVVZBSCM-UHFFFAOYSA-M 0.000 claims 1
- XRHGYUZYPHTUJZ-UHFFFAOYSA-M 4-chlorobenzoate Chemical compound [O-]C(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-M 0.000 claims 1
- JUHPDXOIGLHXTC-UHFFFAOYSA-M 4-fluoro-2-(trifluoromethyl)benzoate Chemical compound [O-]C(=O)C1=CC=C(F)C=C1C(F)(F)F JUHPDXOIGLHXTC-UHFFFAOYSA-M 0.000 claims 1
- WZBPZYCJUADXRS-UHFFFAOYSA-M 4-fluoro-3-(trifluoromethyl)benzoate Chemical compound [O-]C(=O)C1=CC=C(F)C(C(F)(F)F)=C1 WZBPZYCJUADXRS-UHFFFAOYSA-M 0.000 claims 1
- LWGCZCMLPRMKIZ-UHFFFAOYSA-N 4-fluoro-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1F LWGCZCMLPRMKIZ-UHFFFAOYSA-N 0.000 claims 1
- WGAVMKXCDMQVNF-UHFFFAOYSA-M 5-chloro-2-fluorobenzoate Chemical compound [O-]C(=O)C1=CC(Cl)=CC=C1F WGAVMKXCDMQVNF-UHFFFAOYSA-M 0.000 claims 1
- HULDRQRKKXRXBI-UHFFFAOYSA-N 5-chloro-2-methoxybenzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(O)=O HULDRQRKKXRXBI-UHFFFAOYSA-N 0.000 claims 1
- UQXVUTYCTZULCD-UHFFFAOYSA-N 5-cyano-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC(C#N)=CC=C1F UQXVUTYCTZULCD-UHFFFAOYSA-N 0.000 claims 1
- KTCMBLUJFHQKJL-OAHLLOKOSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2,3-difluorobenzoate Chemical compound FC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=C1F KTCMBLUJFHQKJL-OAHLLOKOSA-N 0.000 claims 1
- LNIPFIMSTUUSON-GOSISDBHSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2,4-dimethylbenzoate Chemical compound CC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC(=C1)C LNIPFIMSTUUSON-GOSISDBHSA-N 0.000 claims 1
- YJVUUYULWBPESD-OAHLLOKOSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2,5-difluorobenzoate Chemical compound FC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C(C=C1)F YJVUUYULWBPESD-OAHLLOKOSA-N 0.000 claims 1
- FLCOEPUOBVVIAQ-OAHLLOKOSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2,6-difluorobenzoate Chemical compound FC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C(=CC=C1)F FLCOEPUOBVVIAQ-OAHLLOKOSA-N 0.000 claims 1
- WDZGOXOEOHCWNT-OAHLLOKOSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-chloro-3-fluorobenzoate Chemical compound ClC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=C1F WDZGOXOEOHCWNT-OAHLLOKOSA-N 0.000 claims 1
- JGWMBBXJZRXZLE-OAHLLOKOSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-chloro-5-fluorobenzoate Chemical compound ClC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C(C=C1)F JGWMBBXJZRXZLE-OAHLLOKOSA-N 0.000 claims 1
- VRCXUHXKUREAJZ-OAHLLOKOSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-chloro-6-fluorobenzoate Chemical compound ClC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C(=CC=C1)F VRCXUHXKUREAJZ-OAHLLOKOSA-N 0.000 claims 1
- QFDFQYORPFUCCB-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-ethylbutanoate Chemical compound C(C)C(C(=O)OC[C@@H](CN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)C)CC QFDFQYORPFUCCB-MRXNPFEDSA-N 0.000 claims 1
- YEYXLDOCLKMBGR-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-fluoro-3-methoxybenzoate Chemical compound FC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=C1OC YEYXLDOCLKMBGR-MRXNPFEDSA-N 0.000 claims 1
- IAATXXXRGANTCS-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-fluoro-4-methoxybenzoate Chemical compound FC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC(=C1)OC IAATXXXRGANTCS-MRXNPFEDSA-N 0.000 claims 1
- WVSWGOOMRGGNGC-QGZVFWFLSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-fluoro-4-methylbenzoate Chemical compound FC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC(=C1)C WVSWGOOMRGGNGC-QGZVFWFLSA-N 0.000 claims 1
- WXIISELCUMCXDS-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-fluoro-5-methoxybenzoate Chemical compound FC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C(C=C1)OC WXIISELCUMCXDS-MRXNPFEDSA-N 0.000 claims 1
- RMEYWEJUUAESNL-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-fluoro-6-methoxybenzoate Chemical compound FC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C(=CC=C1)OC RMEYWEJUUAESNL-MRXNPFEDSA-N 0.000 claims 1
- GBLYLBWIWFXFJW-GOSISDBHSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-methoxy-4-methylbenzoate Chemical compound COC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC(=C1)C GBLYLBWIWFXFJW-GOSISDBHSA-N 0.000 claims 1
- LSDUDKOGXCLPAQ-QGZVFWFLSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 2-methylsulfonylbenzoate Chemical compound CS(=O)(=O)C1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=C1 LSDUDKOGXCLPAQ-QGZVFWFLSA-N 0.000 claims 1
- CZPRSLDNRSYNNG-OAHLLOKOSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3,4-difluorobenzoate Chemical compound FC=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1F CZPRSLDNRSYNNG-OAHLLOKOSA-N 0.000 claims 1
- AGNVGDUDDWTKIT-QGZVFWFLSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3,4-dimethylbenzoate Chemical compound CC=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1C AGNVGDUDDWTKIT-QGZVFWFLSA-N 0.000 claims 1
- KVUKOWWHIXIRSG-QGZVFWFLSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-acetylbenzoate Chemical compound C(C)(=O)C=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1 KVUKOWWHIXIRSG-QGZVFWFLSA-N 0.000 claims 1
- RFJJXXPYGBOZGW-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-chloro-2-methoxybenzoate Chemical compound ClC=1C(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1)OC RFJJXXPYGBOZGW-MRXNPFEDSA-N 0.000 claims 1
- BCYXJDDVRJEAAY-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-cyano-4-fluorobenzoate Chemical compound C(#N)C=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1F BCYXJDDVRJEAAY-MRXNPFEDSA-N 0.000 claims 1
- FRHOAVVJUMJUJY-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-cyano-5-fluorobenzoate Chemical compound C(#N)C=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C(C=1)F FRHOAVVJUMJUJY-MRXNPFEDSA-N 0.000 claims 1
- KBWDBXVDFZIKJV-QGZVFWFLSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-cyanobenzoate Chemical compound C(#N)C=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1 KBWDBXVDFZIKJV-QGZVFWFLSA-N 0.000 claims 1
- RYYBEFSOYFYIOB-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-fluoro-2-methoxybenzoate Chemical compound FC=1C(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1)OC RYYBEFSOYFYIOB-MRXNPFEDSA-N 0.000 claims 1
- WSYZQVGTAZKFDC-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-fluoro-4-methoxybenzoate Chemical compound FC=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1OC WSYZQVGTAZKFDC-MRXNPFEDSA-N 0.000 claims 1
- BDKZHDWXONRACA-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-fluorobenzoate Chemical compound FC=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1 BDKZHDWXONRACA-MRXNPFEDSA-N 0.000 claims 1
- UJYXJCDOXSJDNE-QGZVFWFLSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-methoxybenzoate Chemical compound COC=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1 UJYXJCDOXSJDNE-QGZVFWFLSA-N 0.000 claims 1
- SXBHZMBXNNOZSG-HXUWFJFHSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-pyrrolidin-1-ylsulfonylbenzoate Chemical compound N1(CCCC1)S(=O)(=O)C=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1 SXBHZMBXNNOZSG-HXUWFJFHSA-N 0.000 claims 1
- OROZVEPJTNUCRC-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-sulfamoylbenzoate Chemical compound S(N)(=O)(=O)C=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1 OROZVEPJTNUCRC-MRXNPFEDSA-N 0.000 claims 1
- SZPBWHAAQGKJOL-QGZVFWFLSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-acetylbenzoate Chemical compound C(C)(=O)C1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 SZPBWHAAQGKJOL-QGZVFWFLSA-N 0.000 claims 1
- FBXASJOOOSYFRZ-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-chloro-2-methoxybenzoate Chemical compound ClC1=CC(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1)OC FBXASJOOOSYFRZ-MRXNPFEDSA-N 0.000 claims 1
- GAHLFQRARSOHRS-OAHLLOKOSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-chloro-3-fluorobenzoate Chemical compound ClC1=C(C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1)F GAHLFQRARSOHRS-OAHLLOKOSA-N 0.000 claims 1
- GMQCQEJIICLFOS-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-cyano-3-fluorobenzoate Chemical compound C(#N)C1=C(C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1)F GMQCQEJIICLFOS-MRXNPFEDSA-N 0.000 claims 1
- XEFXKTCGARQDSS-QGZVFWFLSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-cyanobenzoate Chemical compound C(#N)C1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 XEFXKTCGARQDSS-QGZVFWFLSA-N 0.000 claims 1
- KTIHDGCPKUTDBG-HXUWFJFHSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-cyclopentylsulfonylbenzoate Chemical compound C1(CCCC1)S(=O)(=O)C1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 KTIHDGCPKUTDBG-HXUWFJFHSA-N 0.000 claims 1
- VZAISOYWPQFOGT-GOSISDBHSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-ethylsulfonylbenzoate Chemical compound C(C)S(=O)(=O)C1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 VZAISOYWPQFOGT-GOSISDBHSA-N 0.000 claims 1
- HAMQDXMBSJNKBM-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-fluoro-2-methoxybenzoate Chemical compound FC1=CC(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1)OC HAMQDXMBSJNKBM-MRXNPFEDSA-N 0.000 claims 1
- ORTXUYXXNHSLLX-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-fluoro-3-methoxybenzoate Chemical compound FC1=C(C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1)OC ORTXUYXXNHSLLX-MRXNPFEDSA-N 0.000 claims 1
- ZCINQNHAYWWVDC-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-fluorobenzoate Chemical compound FC1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 ZCINQNHAYWWVDC-MRXNPFEDSA-N 0.000 claims 1
- CEWBKEQLSLDISI-QGZVFWFLSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-methoxy-3-methylbenzoate Chemical compound COC1=C(C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1)C CEWBKEQLSLDISI-QGZVFWFLSA-N 0.000 claims 1
- DXUSTNQUYSKWDS-GOSISDBHSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-methylbenzoate Chemical compound CC1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 DXUSTNQUYSKWDS-GOSISDBHSA-N 0.000 claims 1
- FODOSXQMFKDLIS-HXUWFJFHSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-morpholin-4-ylsulfonylbenzoate Chemical compound O1CCN(CC1)S(=O)(=O)C1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 FODOSXQMFKDLIS-HXUWFJFHSA-N 0.000 claims 1
- SBRYMKBLIHOTME-LJQANCHMSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-propan-2-ylsulfonylbenzoate Chemical compound C(C)(C)S(=O)(=O)C1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 SBRYMKBLIHOTME-LJQANCHMSA-N 0.000 claims 1
- NEDAXMPQUDQUEA-HXUWFJFHSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-pyrrolidin-1-ylsulfonylbenzoate Chemical compound N1(CCCC1)S(=O)(=O)C1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 NEDAXMPQUDQUEA-HXUWFJFHSA-N 0.000 claims 1
- AQQFDCFFIFRKGD-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-sulfamoylbenzoate Chemical compound S(N)(=O)(=O)C1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 AQQFDCFFIFRKGD-MRXNPFEDSA-N 0.000 claims 1
- YYSYOMMLEHBYOD-OAHLLOKOSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 5-chloro-2-fluorobenzoate Chemical compound ClC=1C=CC(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=1)F YYSYOMMLEHBYOD-OAHLLOKOSA-N 0.000 claims 1
- VTMVJXRMZJHTFN-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 5-chloro-2-methoxybenzoate Chemical compound ClC=1C=CC(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=1)OC VTMVJXRMZJHTFN-MRXNPFEDSA-N 0.000 claims 1
- IUROTAIIAMLFRX-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 5-cyano-2-fluorobenzoate Chemical compound C(#N)C=1C=CC(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=1)F IUROTAIIAMLFRX-MRXNPFEDSA-N 0.000 claims 1
- RPALEWDVNRXSSJ-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 5-fluoro-2-methylbenzoate Chemical compound FC=1C=CC(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=1)C RPALEWDVNRXSSJ-MRXNPFEDSA-N 0.000 claims 1
- LYEFGIFXIOOZGG-QGZVFWFLSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] benzoate Chemical compound C(C1=CC=CC=C1)(=O)OC[C@@H](CN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)C LYEFGIFXIOOZGG-QGZVFWFLSA-N 0.000 claims 1
- BDKZHDWXONRACA-INIZCTEOSA-N [(2S)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-fluorobenzoate Chemical compound FC=1C=C(C(=O)OC[C@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1 BDKZHDWXONRACA-INIZCTEOSA-N 0.000 claims 1
- UJYXJCDOXSJDNE-KRWDZBQOSA-N [(2S)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 3-methoxybenzoate Chemical compound COC=1C=C(C(=O)OC[C@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1 UJYXJCDOXSJDNE-KRWDZBQOSA-N 0.000 claims 1
- ZCINQNHAYWWVDC-INIZCTEOSA-N [(2S)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-fluorobenzoate Chemical compound FC1=CC=C(C(=O)OC[C@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 ZCINQNHAYWWVDC-INIZCTEOSA-N 0.000 claims 1
- DXUSTNQUYSKWDS-SFHVURJKSA-N [(2S)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] 4-methylbenzoate Chemical compound CC1=CC=C(C(=O)OC[C@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 DXUSTNQUYSKWDS-SFHVURJKSA-N 0.000 claims 1
- JBLQTPNTWOTOTM-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 2-chloro-4-fluorobenzoate Chemical compound ClC1=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC(=C1)F JBLQTPNTWOTOTM-UHFFFAOYSA-N 0.000 claims 1
- JZYLTLQSPOQXFX-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 2-chloro-6-fluorobenzoate Chemical compound ClC1=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C(=CC=C1)F JZYLTLQSPOQXFX-UHFFFAOYSA-N 0.000 claims 1
- NTTZJOTXPURPFN-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 2-chlorobenzoate Chemical compound ClC1=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=C1 NTTZJOTXPURPFN-UHFFFAOYSA-N 0.000 claims 1
- UIQRYGMGELAIKG-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 2-ethylbutanoate Chemical compound C(C)C(C(=O)OCC(CN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)(C)C)CC UIQRYGMGELAIKG-UHFFFAOYSA-N 0.000 claims 1
- FVKFKMSADNOZFE-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 2-fluorobenzoate Chemical compound FC1=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=C1 FVKFKMSADNOZFE-UHFFFAOYSA-N 0.000 claims 1
- DXMXIJLZCVPLPS-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 2-methylsulfonylbenzoate Chemical compound CS(=O)(=O)C1=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=C1 DXMXIJLZCVPLPS-UHFFFAOYSA-N 0.000 claims 1
- BCVDRWRWEFDPIG-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3,4-difluorobenzoate Chemical compound FC=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1F BCVDRWRWEFDPIG-UHFFFAOYSA-N 0.000 claims 1
- ZRTRKVSKACOCBU-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3,5-difluorobenzoate Chemical compound FC=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C(C=1)F ZRTRKVSKACOCBU-UHFFFAOYSA-N 0.000 claims 1
- SFOKEVRSFKDIKY-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3-acetylbenzoate Chemical compound C(C)(=O)C=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1 SFOKEVRSFKDIKY-UHFFFAOYSA-N 0.000 claims 1
- BLAXWSKGMOKJKH-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3-carbamoylbenzoate Chemical compound C(N)(=O)C=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1 BLAXWSKGMOKJKH-UHFFFAOYSA-N 0.000 claims 1
- XMWPWPQRKHWXHP-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3-chlorobenzoate Chemical compound ClC=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1 XMWPWPQRKHWXHP-UHFFFAOYSA-N 0.000 claims 1
- NBBUQBSXKKAKAP-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3-cyanobenzoate Chemical compound C(#N)C=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1 NBBUQBSXKKAKAP-UHFFFAOYSA-N 0.000 claims 1
- TWRAEPIJRSDEDA-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3-ethoxybenzoate Chemical compound C(C)OC=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1 TWRAEPIJRSDEDA-UHFFFAOYSA-N 0.000 claims 1
- MRDCKQJWFUWQNE-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3-fluorobenzoate Chemical compound FC=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1 MRDCKQJWFUWQNE-UHFFFAOYSA-N 0.000 claims 1
- GMBZUEZMPIJFAM-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3-methoxybenzoate Chemical compound COC=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1 GMBZUEZMPIJFAM-UHFFFAOYSA-N 0.000 claims 1
- ZOFIAAJWSHWAFM-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3-morpholin-4-ylsulfonylbenzoate Chemical compound O1CCN(CC1)S(=O)(=O)C=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1 ZOFIAAJWSHWAFM-UHFFFAOYSA-N 0.000 claims 1
- GZWJINKDQYIBOU-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3-pyrrolidin-1-ylsulfonylbenzoate Chemical compound N1(CCCC1)S(=O)(=O)C=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1 GZWJINKDQYIBOU-UHFFFAOYSA-N 0.000 claims 1
- BXUFTWLMFRQHSD-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 3-sulfamoylbenzoate Chemical compound S(N)(=O)(=O)C=1C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=CC=1 BXUFTWLMFRQHSD-UHFFFAOYSA-N 0.000 claims 1
- DHWCSUUZJOHLOH-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-acetylbenzoate Chemical compound C(C)(=O)C1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 DHWCSUUZJOHLOH-UHFFFAOYSA-N 0.000 claims 1
- ARWBAGLRSDEEOA-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-carbamoylbenzoate Chemical compound C(N)(=O)C1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 ARWBAGLRSDEEOA-UHFFFAOYSA-N 0.000 claims 1
- PMNIOACXCQNPEE-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-chlorobenzoate Chemical compound ClC1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 PMNIOACXCQNPEE-UHFFFAOYSA-N 0.000 claims 1
- ZTWXPRYURRDKRX-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-cyano-2-fluorobenzoate Chemical compound C(#N)C1=CC(=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1)F ZTWXPRYURRDKRX-UHFFFAOYSA-N 0.000 claims 1
- AQQOGOPZLCFXBI-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-cyano-3-fluorobenzoate Chemical compound C(#N)C1=C(C=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1)F AQQOGOPZLCFXBI-UHFFFAOYSA-N 0.000 claims 1
- DLASZRFRKGLOTD-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-cyanobenzoate Chemical compound C(#N)C1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 DLASZRFRKGLOTD-UHFFFAOYSA-N 0.000 claims 1
- OLEZXAWDLYAVMH-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-ethylsulfonylbenzoate Chemical compound C(C)S(=O)(=O)C1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 OLEZXAWDLYAVMH-UHFFFAOYSA-N 0.000 claims 1
- KFNYCNQYPREYNL-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-fluorobenzoate Chemical compound FC1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 KFNYCNQYPREYNL-UHFFFAOYSA-N 0.000 claims 1
- ATGQNJOQDLUYBD-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-methylbenzoate Chemical compound CC1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 ATGQNJOQDLUYBD-UHFFFAOYSA-N 0.000 claims 1
- FJEZZHJNCUQZQE-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-methylsulfonylbenzoate Chemical compound CS(=O)(=O)C1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 FJEZZHJNCUQZQE-UHFFFAOYSA-N 0.000 claims 1
- BSEGJNWUYJVGAC-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-morpholin-4-ylsulfonylbenzoate Chemical compound O1CCN(CC1)S(=O)(=O)C1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 BSEGJNWUYJVGAC-UHFFFAOYSA-N 0.000 claims 1
- UIVUZQANNIRZFM-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-propan-2-ylsulfonylbenzoate Chemical compound C(C)(C)S(=O)(=O)C1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 UIVUZQANNIRZFM-UHFFFAOYSA-N 0.000 claims 1
- GBKJINMXGNRXSK-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-pyrrolidin-1-ylsulfonylbenzoate Chemical compound N1(CCCC1)S(=O)(=O)C1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 GBKJINMXGNRXSK-UHFFFAOYSA-N 0.000 claims 1
- NNRZXNRJLPUXII-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] 4-sulfamoylbenzoate Chemical compound S(N)(=O)(=O)C1=CC=C(C(=O)OCC(CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)(C)C)C=C1 NNRZXNRJLPUXII-UHFFFAOYSA-N 0.000 claims 1
- DAMNASPZDHKLBB-UHFFFAOYSA-N [3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2,2-dimethylpropyl] cyclopentanecarboxylate Chemical compound C1(CCCC1)C(=O)OCC(CN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)(C)C DAMNASPZDHKLBB-UHFFFAOYSA-N 0.000 claims 1
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims 1
- OEYRKUSFKACRRP-UHFFFAOYSA-N benzoyl piperidine-1-carboxylate Chemical compound C1CCCCN1C(=O)OC(=O)C1=CC=CC=C1 OEYRKUSFKACRRP-UHFFFAOYSA-N 0.000 claims 1
- YXZNVLYXBIIIOB-UHFFFAOYSA-N methyl 3-fluorobenzoate Chemical compound COC(=O)C1=CC=CC(F)=C1 YXZNVLYXBIIIOB-UHFFFAOYSA-N 0.000 claims 1
- LXNFVVDCCWUUKC-UHFFFAOYSA-N methyl 4-chlorobenzoate Chemical compound COC(=O)C1=CC=C(Cl)C=C1 LXNFVVDCCWUUKC-UHFFFAOYSA-N 0.000 claims 1
- OQSJWQNOMXRCEL-UHFFFAOYSA-N methyl 4-methylbenzoate Chemical compound [CH2]C1=CC=C(C(=O)OC)C=C1 OQSJWQNOMXRCEL-UHFFFAOYSA-N 0.000 claims 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims 1
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims 1
- DKBKGTSIBMYJBN-UHFFFAOYSA-N propyl 2-(trifluoromethyl)benzoate Chemical compound CCCOC(=O)C1=CC=CC=C1C(F)(F)F DKBKGTSIBMYJBN-UHFFFAOYSA-N 0.000 claims 1
- FZZUOKABKPIZLI-UHFFFAOYSA-N propyl 2-chloro-4-methylbenzoate Chemical compound ClC1=C(C(=O)OCCC)C=CC(=C1)C FZZUOKABKPIZLI-UHFFFAOYSA-N 0.000 claims 1
- QTMYIAXQVAOUET-UHFFFAOYSA-N propyl 2-chloro-6-fluorobenzoate Chemical compound CCCOC(=O)C1=C(F)C=CC=C1Cl QTMYIAXQVAOUET-UHFFFAOYSA-N 0.000 claims 1
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- HAURMKCUGJUFKD-UHFFFAOYSA-N propyl 3-(4-methylpiperazine-1-carbonyl)benzoate Chemical compound CN1CCN(CC1)C(=O)C=1C=C(C(=O)OCCC)C=CC=1 HAURMKCUGJUFKD-UHFFFAOYSA-N 0.000 claims 1
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- AKDNUSRJPOHNOZ-UHFFFAOYSA-N propyl 3-(trifluoromethyl)benzoate Chemical compound CCCOC(=O)C1=CC=CC(C(F)(F)F)=C1 AKDNUSRJPOHNOZ-UHFFFAOYSA-N 0.000 claims 1
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- GLANJXQECZHTPW-UHFFFAOYSA-N propyl 3-fluoro-2-methoxybenzoate Chemical compound FC=1C(=C(C(=O)OCCC)C=CC=1)OC GLANJXQECZHTPW-UHFFFAOYSA-N 0.000 claims 1
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- WGGSYLZXPAKRDV-UHFFFAOYSA-N propyl 4,4-difluorocyclohexane-1-carboxylate Chemical compound CCCOC(=O)C1CCC(F)(F)CC1 WGGSYLZXPAKRDV-UHFFFAOYSA-N 0.000 claims 1
- JCKHHJGLWVBLIP-UHFFFAOYSA-N propyl 4-(dimethylsulfamoyl)benzoate Chemical compound CCCOC(=O)C1=CC=C(S(=O)(=O)N(C)C)C=C1 JCKHHJGLWVBLIP-UHFFFAOYSA-N 0.000 claims 1
- KRXGXATYGWKWSV-UHFFFAOYSA-N propyl 4-(trifluoromethyl)benzoate Chemical compound CCCOC(=O)C1=CC=C(C(F)(F)F)C=C1 KRXGXATYGWKWSV-UHFFFAOYSA-N 0.000 claims 1
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- UIZIWLVMMOJPRO-UHFFFAOYSA-N propyl 4-fluoro-3-methylbenzoate Chemical compound CCCOC(=O)C1=CC=C(F)C(C)=C1 UIZIWLVMMOJPRO-UHFFFAOYSA-N 0.000 claims 1
- WEHMFTWWOGBHCR-UHFFFAOYSA-N propyl 4-methoxybenzoate Chemical compound CCCOC(=O)C1=CC=C(OC)C=C1 WEHMFTWWOGBHCR-UHFFFAOYSA-N 0.000 claims 1
- FJCLCPNLEYNZTJ-UHFFFAOYSA-N propyl 5-chloro-2-methylbenzoate Chemical compound ClC=1C=CC(=C(C(=O)OCCC)C=1)C FJCLCPNLEYNZTJ-UHFFFAOYSA-N 0.000 claims 1
- TUHJOURQQSUKPJ-UHFFFAOYSA-N propyl 5-fluoro-2-methoxybenzoate Chemical compound CCCOC(=O)C1=CC(F)=CC=C1OC TUHJOURQQSUKPJ-UHFFFAOYSA-N 0.000 claims 1
- RGCPXUDRWFNICP-UHFFFAOYSA-N propyl 5-fluoro-2-methylbenzoate Chemical compound CCCOC(=O)C1=CC(F)=CC=C1C RGCPXUDRWFNICP-UHFFFAOYSA-N 0.000 claims 1
- 229940090181 propyl acetate Drugs 0.000 claims 1
- WRTSXKKAXLYBSH-UHFFFAOYSA-N trifluoromethyl benzoate Chemical compound FC(F)(F)OC(=O)C1=CC=CC=C1 WRTSXKKAXLYBSH-UHFFFAOYSA-N 0.000 claims 1
- 125000003884 phenylalkyl group Chemical group 0.000 abstract 1
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 49
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- 238000006243 chemical reaction Methods 0.000 description 25
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 239000003480 eluent Substances 0.000 description 22
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- 230000008569 process Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- WDYZSLQVKDHVME-UHFFFAOYSA-N propyl 4-ethylbenzoate Chemical compound CCCOC(=O)C1=CC=C(CC)C=C1 WDYZSLQVKDHVME-UHFFFAOYSA-N 0.000 description 1
- UKPBXIFLSVLDPA-UHFFFAOYSA-N propylhydrazine Chemical compound CCCNN UKPBXIFLSVLDPA-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- JAQJOJXZXMYDFO-UHFFFAOYSA-N pyrazolo[4,3-d]diazepine Chemical class N1=NC=C2C1=CC=NN=C2 JAQJOJXZXMYDFO-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000012950 reanalysis Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- ATCCIZURPPEVIZ-SCSAIBSYSA-N roche ester Chemical compound COC(=O)[C@H](C)CO ATCCIZURPPEVIZ-SCSAIBSYSA-N 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 229950006828 timegadine Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- PZMFITAWSPYPDV-UHFFFAOYSA-N undecane-2,4-dione Chemical compound CCCCCCCC(=O)CC(C)=O PZMFITAWSPYPDV-UHFFFAOYSA-N 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/20—Spiro-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2016/080548 WO2018108230A1 (en) | 2016-12-12 | 2016-12-12 | Substituted pyrazoloazepin-4-ones and their use as phosphodiesterase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2875128T3 true ES2875128T3 (es) | 2021-11-08 |
Family
ID=57539258
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16809388T Active ES2875128T3 (es) | 2016-12-12 | 2016-12-12 | Pirazoloazepin-8-onas sustituidas y su uso como inhibidores de la fosfodiesterasa |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US10906915B2 (https=) |
| EP (1) | EP3551633B1 (https=) |
| JP (1) | JP6850886B2 (https=) |
| CN (1) | CN110088108B (https=) |
| DK (1) | DK3551633T3 (https=) |
| ES (1) | ES2875128T3 (https=) |
| RU (1) | RU2762279C2 (https=) |
| WO (1) | WO2018108230A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3551632B1 (en) * | 2016-12-12 | 2024-06-12 | UNION therapeutics A/S | Substituted pyrazoloazepin-4-ones and their use as phosphodiesterase inhibitors |
| DK3642210T3 (da) | 2017-06-20 | 2024-12-09 | Union Therapeutics As | Fremgangsmåder til fremstilling af heterocykliske 1,3-benzodioxolforbindelser |
| PT3724196T (pt) | 2017-12-15 | 2023-01-13 | Union Therapeutics As | Azetidina di-hidrotienopiridinas substituídas e a sua utilização como inibidores de fosfodiesterase |
| GB202306662D0 (en) | 2023-05-05 | 2023-06-21 | Union Therapeutics As | Dosage regimen |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2803299B1 (fr) * | 2000-01-05 | 2004-09-17 | Warner Lambert Co | NOUVELLES PYRAZOLO [4,3-e] DIAZEPINES SUBSTITUEES, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT, UTILISATION A TITRE DE MEDICAMENT ET PROCEDES POUR LEUR PREPARATION |
| WO2004098520A2 (en) | 2003-05-01 | 2004-11-18 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| TW200745106A (en) * | 2005-10-03 | 2007-12-16 | Astrazeneca Ab | Chemical compounds |
| ES2372320T3 (es) | 2006-11-15 | 2012-01-18 | Vertex Pharmceuticals Incorporated | Compuestos útiles como inhibidores de proteínas quinasas. |
| CA2676933C (en) * | 2007-02-28 | 2015-09-29 | Leo Pharma A/S | Novel phosphodiesterase inhibitors |
| GB0704652D0 (en) | 2007-03-09 | 2007-04-18 | Syngenta Participations Ag | Novel herbicides |
| AR084070A1 (es) * | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
-
2016
- 2016-12-12 JP JP2019531209A patent/JP6850886B2/ja not_active Expired - Fee Related
- 2016-12-12 DK DK16809388.8T patent/DK3551633T3/da active
- 2016-12-12 WO PCT/EP2016/080548 patent/WO2018108230A1/en not_active Ceased
- 2016-12-12 US US16/468,420 patent/US10906915B2/en active Active
- 2016-12-12 ES ES16809388T patent/ES2875128T3/es active Active
- 2016-12-12 RU RU2019121006A patent/RU2762279C2/ru active
- 2016-12-12 EP EP16809388.8A patent/EP3551633B1/en active Active
- 2016-12-12 CN CN201680091502.7A patent/CN110088108B/zh not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN110088108A (zh) | 2019-08-02 |
| RU2019121006A (ru) | 2021-01-12 |
| US20200010477A1 (en) | 2020-01-09 |
| US10906915B2 (en) | 2021-02-02 |
| RU2019121006A3 (https=) | 2021-01-12 |
| JP6850886B2 (ja) | 2021-03-31 |
| JP2020500920A (ja) | 2020-01-16 |
| CN110088108B (zh) | 2024-06-14 |
| DK3551633T3 (da) | 2021-06-28 |
| RU2762279C2 (ru) | 2021-12-17 |
| EP3551633A1 (en) | 2019-10-16 |
| EP3551633B1 (en) | 2021-03-31 |
| WO2018108230A1 (en) | 2018-06-21 |
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