RU2762279C2 - Замещенные пиразолоазепин-4-оны и их применение в качестве ингибиторов фосфодиэстеразы - Google Patents

Info

Publication number

RU2762279C2

RU2762279C2 RU2019121006A RU2019121006A RU2762279C2 RU 2762279 C2 RU2762279 C2 RU 2762279C2 RU 2019121006 A RU2019121006 A RU 2019121006A RU 2019121006 A RU2019121006 A RU 2019121006A RU 2762279 C2 RU2762279 C2 RU 2762279C2

Authority

RU

Russia

Prior art keywords

tetrahydropyran

ethyl

pyrazolo

dihydro

oxospiro

Prior art date

2016-12-12

Links

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• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title 1
• 239000002571 phosphodiesterase inhibitor Substances 0.000 title 1
• -1 cyano, hydroxyl Chemical group 0.000 claims abstract description 645
• 150000001875 compounds Chemical class 0.000 claims abstract description 359
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 197
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 120
• 239000001257 hydrogen Substances 0.000 claims abstract description 120
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 84
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 70
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 70
• 125000001424 substituent group Chemical group 0.000 claims abstract description 58
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 56
• 150000002367 halogens Chemical class 0.000 claims abstract description 54
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 51
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 47
• 150000003839 salts Chemical class 0.000 claims abstract description 44
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 43
• 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims abstract description 40
• 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims abstract description 40
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 39
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 37
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 36
• 201000010099 disease Diseases 0.000 claims abstract description 26
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 23
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 23
• 238000011282 treatment Methods 0.000 claims abstract description 23
• 208000035475 disorder Diseases 0.000 claims abstract description 21
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 20
• 125000003566 oxetanyl group Chemical group 0.000 claims abstract description 19
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 17
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 14
• 239000003814 drug Substances 0.000 claims abstract description 12
• 208000017520 skin disease Diseases 0.000 claims abstract description 12
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims abstract description 9
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 9
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
• 229940095102 methyl benzoate Drugs 0.000 claims description 80
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 62
• 150000002431 hydrogen Chemical class 0.000 claims description 50
• 238000000034 method Methods 0.000 claims description 49
• 201000004624 Dermatitis Diseases 0.000 claims description 25
• 238000002360 preparation method Methods 0.000 claims description 23
• 206010040799 Skin atrophy Diseases 0.000 claims description 15
• QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 14
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 13
• 201000008937 atopic dermatitis Diseases 0.000 claims description 13
• FNJPHLBTJIHHPG-UHFFFAOYSA-N 2-(2-cyanophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=CC=C1C#N FNJPHLBTJIHHPG-UHFFFAOYSA-N 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 201000004681 Psoriasis Diseases 0.000 claims description 10
• 208000004631 alopecia areata Diseases 0.000 claims description 10
• 208000002874 Acne Vulgaris Diseases 0.000 claims description 9
• 208000003251 Pruritus Diseases 0.000 claims description 9
• 206010000496 acne Diseases 0.000 claims description 9
• 208000010668 atopic eczema Diseases 0.000 claims description 9
• LPNBBFKOUUSUDB-UHFFFAOYSA-M p-toluate Chemical compound CC1=CC=C(C([O-])=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-M 0.000 claims description 9
• 206010012442 Dermatitis contact Diseases 0.000 claims description 8
• 206010061218 Inflammation Diseases 0.000 claims description 8
• 206010028980 Neoplasm Diseases 0.000 claims description 8
• 206010051246 Photodermatosis Diseases 0.000 claims description 8
• 206010039793 Seborrhoeic dermatitis Diseases 0.000 claims description 8
• 208000024780 Urticaria Diseases 0.000 claims description 8
• 201000011510 cancer Diseases 0.000 claims description 8
• 208000010247 contact dermatitis Diseases 0.000 claims description 8
• 230000004054 inflammatory process Effects 0.000 claims description 8
• 230000008845 photoaging Effects 0.000 claims description 8
• 230000002062 proliferating effect Effects 0.000 claims description 8
• 208000008742 seborrheic dermatitis Diseases 0.000 claims description 8
• 150000003431 steroids Chemical class 0.000 claims description 8
• 201000004384 Alopecia Diseases 0.000 claims description 7
• 231100000360 alopecia Toxicity 0.000 claims description 7
• 230000009759 skin aging Effects 0.000 claims description 7
• BZSXEZOLBIJVQK-UHFFFAOYSA-M 2-methylsulfonylbenzoate Chemical compound CS(=O)(=O)C1=CC=CC=C1C([O-])=O BZSXEZOLBIJVQK-UHFFFAOYSA-M 0.000 claims description 6
• CHZPJUSFUDUEMZ-UHFFFAOYSA-M 3-acetylbenzoate Chemical compound CC(=O)C1=CC=CC(C([O-])=O)=C1 CHZPJUSFUDUEMZ-UHFFFAOYSA-M 0.000 claims description 6
• 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 description 6
• NAETXYOXMDYNLE-UHFFFAOYSA-N 3-sulfamoylbenzoic acid Chemical compound NS(=O)(=O)C1=CC=CC(C(O)=O)=C1 NAETXYOXMDYNLE-UHFFFAOYSA-N 0.000 claims description 6
• BFTPXPCTGHARJF-UHFFFAOYSA-M 4-(morpholine-4-carbonyl)benzoate Chemical compound C1=CC(C(=O)[O-])=CC=C1C(=O)N1CCOCC1 BFTPXPCTGHARJF-UHFFFAOYSA-M 0.000 claims description 6
• 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 description 6
• UCAGLBKTLXCODC-UHFFFAOYSA-M 4-sulfamoylbenzoate Chemical compound NS(=O)(=O)C1=CC=C(C([O-])=O)C=C1 UCAGLBKTLXCODC-UHFFFAOYSA-M 0.000 claims description 6
• XSIFPSYPOVKYCO-UHFFFAOYSA-N benzoic acid butyl ester Natural products CCCCOC(=O)C1=CC=CC=C1 XSIFPSYPOVKYCO-UHFFFAOYSA-N 0.000 claims description 6
• 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 5
• 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 description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• 241001465754 Metazoa Species 0.000 claims description 4
• BKYWPNROPGQIFZ-UHFFFAOYSA-M 2,4-dimethylbenzoate Chemical compound CC1=CC=C(C([O-])=O)C(C)=C1 BKYWPNROPGQIFZ-UHFFFAOYSA-M 0.000 claims description 3
• FBRJYBGLCHWYOE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(F)(F)F FBRJYBGLCHWYOE-UHFFFAOYSA-N 0.000 claims description 3
• 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 description 3
• 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 description 3
• OPVAJFQBSDUNQA-UHFFFAOYSA-M 3,4-dimethylbenzoate Chemical compound CC1=CC=C(C([O-])=O)C=C1C OPVAJFQBSDUNQA-UHFFFAOYSA-M 0.000 claims description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• MLPBAEAJTJCAIQ-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-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 MLPBAEAJTJCAIQ-MRXNPFEDSA-N 0.000 claims description 3
• DZCKIELUOUTBRC-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-methylpropanoate Chemical compound CC(C(=O)OC[C@@H](CN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)C)C DZCKIELUOUTBRC-OAHLLOKOSA-N 0.000 claims description 3
• 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 description 3
• FAIJAUUNVKMDRQ-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-chloro-2-fluorobenzoate Chemical compound ClC=1C(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1)F FAIJAUUNVKMDRQ-OAHLLOKOSA-N 0.000 claims description 3
• 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 description 3
• SLHHHRCIAZTHQD-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-chloro-4-fluorobenzoate Chemical compound ClC=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1F SLHHHRCIAZTHQD-OAHLLOKOSA-N 0.000 claims description 3
• HSXUCJRLPCCFND-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-4-methoxybenzoate Chemical compound ClC=1C=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=1OC HSXUCJRLPCCFND-MRXNPFEDSA-N 0.000 claims description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• NACFPQBPGMUWCJ-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-2-fluorobenzoate Chemical compound ClC1=CC(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1)F NACFPQBPGMUWCJ-OAHLLOKOSA-N 0.000 claims description 3
• 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 description 3
• IUUVLVOAHKUQHO-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-methylbenzoate Chemical compound ClC1=CC(=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1)C IUUVLVOAHKUQHO-MRXNPFEDSA-N 0.000 claims description 3
• 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 description 3
• WAFFFSLUBCHINL-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-chlorobenzoate Chemical compound ClC1=CC=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 WAFFFSLUBCHINL-MRXNPFEDSA-N 0.000 claims description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• VRNARGMXFRXSDS-MRXNPFEDSA-N [(2R)-3-(3-ethyl-4-oxospiro[6,8-dihydro-5H-pyrazolo[4,3-c]azepine-7,4'-oxane]-1-yl)-2-methylpropyl] cyclopentanecarboxylate Chemical compound C1(CCCC1)C(=O)OC[C@@H](CN1N=C(C=2C(NCC3(CCOCC3)CC=21)=O)CC)C VRNARGMXFRXSDS-MRXNPFEDSA-N 0.000 claims description 3
• 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 description 3
• 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 description 3
• WAFFFSLUBCHINL-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-chlorobenzoate Chemical compound ClC1=CC=C(C(=O)OC[C@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=C1 WAFFFSLUBCHINL-INIZCTEOSA-N 0.000 claims description 3
• 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 description 3
• LYEFGIFXIOOZGG-KRWDZBQOSA-N [(2S)-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-KRWDZBQOSA-N 0.000 claims description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims description 3
• LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 3
• YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 3
• 229940090181 propyl acetate Drugs 0.000 claims description 3
• YXHWFMQRECDLHQ-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-chloro-3-methoxybenzoate Chemical compound ClC1=C(C(=O)OC[C@@H](CN2N=C(C=3C(NCC4(CCOCC4)CC=32)=O)CC)C)C=CC=C1OC YXHWFMQRECDLHQ-MRXNPFEDSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• 239000003981 vehicle Substances 0.000 claims description 2
• SOWDWUPMHVDZGL-UHFFFAOYSA-N 2-methoxy-4-methylbenzoic acid Chemical compound COC1=CC(C)=CC=C1C(O)=O SOWDWUPMHVDZGL-UHFFFAOYSA-N 0.000 claims 1
• OXUUNDMDOOXPKY-UHFFFAOYSA-M 4-chloro-3-methoxybenzoate Chemical compound COC1=CC(C([O-])=O)=CC=C1Cl OXUUNDMDOOXPKY-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
• BBYDXOIZLAWGSL-UHFFFAOYSA-M 4-fluorobenzoate Chemical compound [O-]C(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-M 0.000 claims 1
• 230000032683 aging Effects 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
• 230000000694 effects Effects 0.000 abstract description 5
• 239000000126 substance Substances 0.000 abstract description 4
• 229910003827 NRaRb Inorganic materials 0.000 abstract 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
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• 239000000203 mixture Substances 0.000 description 109
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• 239000000243 solution Substances 0.000 description 69
• 238000005481 NMR spectroscopy Methods 0.000 description 53
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• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 26
• 238000006243 chemical reaction Methods 0.000 description 25
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