NO314400B1 - Substituerte tricykliske forbindelser - Google Patents

Info

Publication number

NO314400B1

NO314400B1 NO19991821A NO991821A NO314400B1 NO 314400 B1 NO314400 B1 NO 314400B1 NO 19991821 A NO19991821 A NO 19991821A NO 991821 A NO991821 A NO 991821A NO 314400 B1 NO314400 B1 NO 314400B1

Authority

NO

Norway

Prior art keywords

methyl

hydroxy

oxyacetic acid

carbamoyl

benzyl

Prior art date

1998-04-17

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 114
• 238000011282 treatment Methods 0.000 claims abstract description 29
• 206010040070 Septic Shock Diseases 0.000 claims abstract description 5
• 230000036303 septic shock Effects 0.000 claims abstract description 5
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 709
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 240
• 239000002253 acid Substances 0.000 claims description 166
• 238000002360 preparation method Methods 0.000 claims description 143
• -1 tri-(1-methylethyl)silyl Chemical group 0.000 claims description 126
• 150000004702 methyl esters Chemical class 0.000 claims description 76
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
• YAQSQUUCVARXHF-UHFFFAOYSA-N methyl 5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CCC(=O)C2=C1NC1=C2C(C(=O)OC)=CC=C1 YAQSQUUCVARXHF-UHFFFAOYSA-N 0.000 claims description 29
• UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 28
• 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims description 26
• 159000000000 sodium salts Chemical class 0.000 claims description 26
• 150000002148 esters Chemical class 0.000 claims description 19
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 17
• 206010003246 arthritis Diseases 0.000 claims description 17
• FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 claims description 15
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 13
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
• 150000003839 salts Chemical class 0.000 claims description 9
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 claims description 9
• PHRABVHYUHIYGY-UHFFFAOYSA-N 1-methylnaphthalene Chemical group C1=CC=C2C([CH2])=CC=CC2=C1 PHRABVHYUHIYGY-UHFFFAOYSA-N 0.000 claims description 8
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 8
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
• 201000010099 disease Diseases 0.000 claims description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• GRNUVEMCUGCDDO-UHFFFAOYSA-N methyl 7-methyl-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1C(C)CC(=O)C2=C1NC1=C2C(C(=O)OC)=CC=C1 GRNUVEMCUGCDDO-UHFFFAOYSA-N 0.000 claims description 8
• OXQCZJHYRFSEQM-UHFFFAOYSA-N 2-[5-carbamoyl-2-methyl-9-[(3-methylphenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound CC1=CC=CC(CN2C3=CC(C)=CC(OCC(O)=O)=C3C3=C(C(N)=O)C=CC=C32)=C1 OXQCZJHYRFSEQM-UHFFFAOYSA-N 0.000 claims description 7
• UJSZZKJIGGAMHM-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2-methylphenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound CC1=CC=CC=C1CN1C2=CC=CC(C(N)=O)=C2C2=C(OCC(O)=O)C=CC=C21 UJSZZKJIGGAMHM-UHFFFAOYSA-N 0.000 claims description 7
• GSUXBSRHWJBQBV-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3-fluorophenyl)methyl]-2-methylcarbazol-4-yl]oxyacetic acid Chemical compound C=1C(C)=CC(OCC(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC(F)=C1 GSUXBSRHWJBQBV-UHFFFAOYSA-N 0.000 claims description 7
• SKVCADFJTHKAEY-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3-iodophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(I)=C1 SKVCADFJTHKAEY-UHFFFAOYSA-N 0.000 claims description 7
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 7
• 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims description 7
• 102000005473 Secretory Phospholipases A2 Human genes 0.000 claims description 7
• 108010031873 Secretory Phospholipases A2 Proteins 0.000 claims description 7
• XRRDFIPYLFCYLU-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical group [CH2]C1=CC(C)=CC(C)=C1 XRRDFIPYLFCYLU-UHFFFAOYSA-N 0.000 claims description 6
• HWVCTTFKEFUZSR-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-2-phenylcarbazol-4-yl)oxyacetic acid Chemical compound C12=CC(C=3C=CC=CC=3)=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1 HWVCTTFKEFUZSR-UHFFFAOYSA-N 0.000 claims description 6
• URFXAPISJQEWEH-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2,6-dichlorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=C(Cl)C=CC=C1Cl URFXAPISJQEWEH-UHFFFAOYSA-N 0.000 claims description 6
• AKPJTFHUTNPVJJ-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2-cyanophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1C#N AKPJTFHUTNPVJJ-UHFFFAOYSA-N 0.000 claims description 6
• MQZAJAXITWPMFM-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2-fluorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1F MQZAJAXITWPMFM-UHFFFAOYSA-N 0.000 claims description 6
• KQQRGQBJPMVABZ-UHFFFAOYSA-N 2-[5-carbamoyl-9-[[2-(trifluoromethyl)phenyl]methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1C(F)(F)F KQQRGQBJPMVABZ-UHFFFAOYSA-N 0.000 claims description 6
• 208000012659 Joint disease Diseases 0.000 claims description 6
• 239000012453 solvate Substances 0.000 claims description 6
• YIWKRIZOIPDUPO-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-1-methylcarbazol-4-yl)oxyacetic acid Chemical compound CC1=CC=C(OCC(O)=O)C(C2=C(C(N)=O)C=CC=C22)=C1N2CC1=CC=CC=C1 YIWKRIZOIPDUPO-UHFFFAOYSA-N 0.000 claims description 5
• AAYKHTVNNLLGLP-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-2-methylcarbazol-4-yl)oxyacetic acid Chemical compound C=1C(C)=CC(OCC(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 AAYKHTVNNLLGLP-UHFFFAOYSA-N 0.000 claims description 5
• YAENEAAYRCUGQB-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3,5-dimethylphenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound CC1=CC(C)=CC(CN2C3=CC=CC(=C3C3=C(OCC(O)=O)C=CC=C32)C(N)=O)=C1 YAENEAAYRCUGQB-UHFFFAOYSA-N 0.000 claims description 5
• JCJMBFNXBWSTLL-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3-phenoxyphenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC(C=1)=CC=CC=1OC1=CC=CC=C1 JCJMBFNXBWSTLL-UHFFFAOYSA-N 0.000 claims description 5
• APSSLGLEOLPZAI-UHFFFAOYSA-N 9-benzyl-5-[2-(methanesulfonamido)ethoxy]-7-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide Chemical compound C12=CC(OC)=CC(OCCNS(C)(=O)=O)=C2C=2C(C(N)=O)CCCC=2N1CC1=CC=CC=C1 APSSLGLEOLPZAI-UHFFFAOYSA-N 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 208000014674 injury Diseases 0.000 claims description 5
• 229940002612 prodrug Drugs 0.000 claims description 5
• 239000000651 prodrug Substances 0.000 claims description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• UFJILQXRMNERCL-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoylcarbazol-4-yl)oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1 UFJILQXRMNERCL-UHFFFAOYSA-N 0.000 claims description 4
• CRXQYSQDOBKHNV-UHFFFAOYSA-N 2-[(9-benzyl-5-carbamoyl-5,6,7,8-tetrahydrocarbazol-4-yl)oxy]acetic acid Chemical compound NC(=O)C1CCCC2=C1C1=C(OCC(O)=O)C=CC=C1N2CC1=CC=CC=C1 CRXQYSQDOBKHNV-UHFFFAOYSA-N 0.000 claims description 4
• FRZSYHNHELRNDK-UHFFFAOYSA-N 2-[9-[(2-benzylphenyl)methyl]-5-carbamoylcarbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1CC1=CC=CC=C1 FRZSYHNHELRNDK-UHFFFAOYSA-N 0.000 claims description 4
• YSYSKDYLPVNKKJ-UHFFFAOYSA-N 9-benzyl-5-(cyanomethoxy)-7-methoxycarbazole-4-carboxamide Chemical compound C=1C(OC)=CC(OCC#N)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 YSYSKDYLPVNKKJ-UHFFFAOYSA-N 0.000 claims description 4
• AELSAUYZEFGGJU-UHFFFAOYSA-N 9-benzyl-5-[2-(methanesulfonamido)ethoxy]-7-methoxycarbazole-4-carboxamide Chemical compound C=1C(OC)=CC(OCCNS(C)(=O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 AELSAUYZEFGGJU-UHFFFAOYSA-N 0.000 claims description 4
• XABCYFUHAKJZCS-UHFFFAOYSA-N 9-benzyl-8-fluoro-5-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide Chemical compound C1=2CCCC(C(N)=O)C=2C=2C(OC)=CC=C(F)C=2N1CC1=CC=CC=C1 XABCYFUHAKJZCS-UHFFFAOYSA-N 0.000 claims description 4
• LDPRPCQCLNSMAO-UHFFFAOYSA-N 9h-carbazole-4-carboxamide Chemical compound N1C2=CC=CC=C2C2=C1C=CC=C2C(=O)N LDPRPCQCLNSMAO-UHFFFAOYSA-N 0.000 claims description 4
• 208000036487 Arthropathies Diseases 0.000 claims description 4
• 206010006448 Bronchiolitis Diseases 0.000 claims description 4
• 208000004575 Infectious Arthritis Diseases 0.000 claims description 4
• 206010006451 bronchitis Diseases 0.000 claims description 4
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
• 229910003002 lithium salt Inorganic materials 0.000 claims description 4
• 159000000002 lithium salts Chemical class 0.000 claims description 4
• NCFKVOYLJUVJPQ-UHFFFAOYSA-N methyl 8-[(3-chlorophenyl)methyl]-5-hydroxy-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC(Cl)=C1 NCFKVOYLJUVJPQ-UHFFFAOYSA-N 0.000 claims description 4
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
• 208000002574 reactive arthritis Diseases 0.000 claims description 4
• PRAUIYBTAAOMCZ-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-2-methoxycarbazol-4-yl)oxypropanoic acid Chemical compound C=1C(OC)=CC(OC(C)C(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 PRAUIYBTAAOMCZ-UHFFFAOYSA-N 0.000 claims description 3
• LUURCHSHYLGPEG-UHFFFAOYSA-N 2-[(9-benzyl-5-carbamoyl-1-fluoro-5,6,7,8-tetrahydrocarbazol-4-yl)oxy]acetic acid Chemical compound NC(=O)C1CCCC2=C1C1=C(OCC(O)=O)C=CC(F)=C1N2CC1=CC=CC=C1 LUURCHSHYLGPEG-UHFFFAOYSA-N 0.000 claims description 3
• OCQARBMASQXXGZ-UHFFFAOYSA-N 2-[(9-benzyl-5-carbamoyl-1-methyl-5,6,7,8-tetrahydrocarbazol-4-yl)oxy]acetic acid Chemical compound C1=2C(C)=CC=C(OCC(O)=O)C=2C=2C(C(N)=O)CCCC=2N1CC1=CC=CC=C1 OCQARBMASQXXGZ-UHFFFAOYSA-N 0.000 claims description 3
• VRMKRGKLFIJSNY-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2,6-difluorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=C(F)C=CC=C1F VRMKRGKLFIJSNY-UHFFFAOYSA-N 0.000 claims description 3
• LCPAHBQVBUXTEZ-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3-cyanophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(C#N)=C1 LCPAHBQVBUXTEZ-UHFFFAOYSA-N 0.000 claims description 3
• KWBVGNHCBQIRTN-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3-fluorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(F)=C1 KWBVGNHCBQIRTN-UHFFFAOYSA-N 0.000 claims description 3
• IKVWXTBYJHSVHF-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3-methylphenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound CC1=CC=CC(CN2C3=CC=CC(=C3C3=C(OCC(O)=O)C=CC=C32)C(N)=O)=C1 IKVWXTBYJHSVHF-UHFFFAOYSA-N 0.000 claims description 3
• CGZZUCYZEGYRAT-UHFFFAOYSA-N 9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide Chemical compound C12=CC(OC)=CC(OC)=C2C=2C(C(N)=O)CCCC=2N1CC1=CC=CC=C1 CGZZUCYZEGYRAT-UHFFFAOYSA-N 0.000 claims description 3
• MAWQJLBAPRFZIH-UHFFFAOYSA-N 9-benzyl-5,7-dimethoxycarbazole-4-carboxamide Chemical compound C=1C(OC)=CC(OC)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 MAWQJLBAPRFZIH-UHFFFAOYSA-N 0.000 claims description 3
• ILIKMDNKNZVOMD-UHFFFAOYSA-N 9-benzyl-5-hydroxy-7-methoxycarbazole-4-carboxamide Chemical compound C=1C(OC)=CC(O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 ILIKMDNKNZVOMD-UHFFFAOYSA-N 0.000 claims description 3
• GWSIUDSDXNVENV-UHFFFAOYSA-N 9-benzyl-7-(4-chlorophenyl)-5-hydroxycarbazole-4-carboxamide Chemical compound C12=CC(C=3C=CC(Cl)=CC=3)=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1 GWSIUDSDXNVENV-UHFFFAOYSA-N 0.000 claims description 3
• DVQREHPZPZCGLD-UHFFFAOYSA-N 9-benzyl-8-fluoro-5-methoxycarbazole-4-carboxamide Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OC)=CC=C(F)C=2N1CC1=CC=CC=C1 DVQREHPZPZCGLD-UHFFFAOYSA-N 0.000 claims description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
• NLFVLWRTYIDKGT-UHFFFAOYSA-N COC(COC1=CC(=CC=2N(C3=CC=CC(=C3C1=2)C(N)=O)CC1=CC=CC=C1)CO[Si](C(C)C)(C(C)C)C(C)C)=O Chemical compound COC(COC1=CC(=CC=2N(C3=CC=CC(=C3C1=2)C(N)=O)CC1=CC=CC=C1)CO[Si](C(C)C)(C(C)C)C(C)C)=O NLFVLWRTYIDKGT-UHFFFAOYSA-N 0.000 claims description 3
• 206010033645 Pancreatitis Diseases 0.000 claims description 3
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
• 201000010105 allergic rhinitis Diseases 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
• 150000003857 carboxamides Chemical class 0.000 claims description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• SWWDNZRFRCJACD-UHFFFAOYSA-N ethyl 9-benzyl-8-fluoro-5-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxylate Chemical compound CCOC(=O)C1CCCC2=C1C1=C(OC)C=CC(F)=C1N2CC1=CC=CC=C1 SWWDNZRFRCJACD-UHFFFAOYSA-N 0.000 claims description 3
• 208000002085 hemarthrosis Diseases 0.000 claims description 3
• 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 3
• QCYHHHHOQGEKIE-UHFFFAOYSA-N methyl 2-(2-methoxyphenyl)-3-nitrobenzoate Chemical group COC(=O)C1=CC=CC([N+]([O-])=O)=C1C1=CC=CC=C1OC QCYHHHHOQGEKIE-UHFFFAOYSA-N 0.000 claims description 3
• NIRLBKXYTDHSFZ-UHFFFAOYSA-N methyl 2-bromo-3-[(4-methyl-6-oxocyclohexen-1-yl)amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2C(CC(C)CC=2)=O)=C1Br NIRLBKXYTDHSFZ-UHFFFAOYSA-N 0.000 claims description 3
• SWIUIZXMNZTCRX-UHFFFAOYSA-N methyl 7-(hydroxymethyl)-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1C(CO)CC(=O)C2=C1NC1=C2C(C(=O)OC)=CC=C1 SWIUIZXMNZTCRX-UHFFFAOYSA-N 0.000 claims description 3
• PKFVGCGERGKRQI-UHFFFAOYSA-N methyl 9-benzyl-5-hydroxy-7-phenylcarbazole-4-carboxylate Chemical compound C12=CC(C=3C=CC=CC=3)=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 PKFVGCGERGKRQI-UHFFFAOYSA-N 0.000 claims description 3
• VJZMHAFNPNAFCS-UHFFFAOYSA-N methyl 9-benzyl-5-hydroxy-7-propan-2-ylcarbazole-4-carboxylate Chemical compound C12=CC(C(C)C)=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 VJZMHAFNPNAFCS-UHFFFAOYSA-N 0.000 claims description 3
• ZHYOTVKRNRGRAI-UHFFFAOYSA-N methyl 9-benzyl-5-oxo-7-pentyl-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound O=C1CC(CCCCC)CC2=C1C1=C(C(=O)OC)C=CC=C1N2CC1=CC=CC=C1 ZHYOTVKRNRGRAI-UHFFFAOYSA-N 0.000 claims description 3
• XFTAOPDANGNLBE-UHFFFAOYSA-N methyl 9-benzyl-5-oxo-7-phenyl-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CC(C=3C=CC=CC=3)CC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 XFTAOPDANGNLBE-UHFFFAOYSA-N 0.000 claims description 3
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
• 230000035939 shock Effects 0.000 claims description 3
• 230000008733 trauma Effects 0.000 claims description 3
• LUMYPAZSFDGHFI-UHFFFAOYSA-N 2-[9-benzyl-5-carbamoyl-2-[tri(propan-2-yl)silyloxymethyl]carbazol-4-yl]oxyacetic acid Chemical compound C=1C(CO[Si](C(C)C)(C(C)C)C(C)C)=CC(OCC(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 LUMYPAZSFDGHFI-UHFFFAOYSA-N 0.000 claims description 2
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
• DRRPBTBDXRFNRV-UHFFFAOYSA-N 5-hydroxy-7-methyl-8-[(3-methylphenyl)methyl]-9h-carbazole-4-carboxamide Chemical compound CC1=CC=CC(CC=2C3=C(C4=C(C(N)=O)C=CC=C4N3)C(O)=CC=2C)=C1 DRRPBTBDXRFNRV-UHFFFAOYSA-N 0.000 claims description 2
• PKWKOZFVBKURBY-UHFFFAOYSA-N 5-hydroxy-8-(pyridin-2-ylmethyl)-9h-carbazole-4-carboxamide Chemical compound C1=CC(O)=C2C=3C(C(=O)N)=CC=CC=3NC2=C1CC1=CC=CC=N1 PKWKOZFVBKURBY-UHFFFAOYSA-N 0.000 claims description 2
• KHDBUZYUKAXECE-UHFFFAOYSA-N 5-hydroxy-8-(pyridin-3-ylmethyl)-9h-carbazole-4-carboxamide Chemical compound C1=CC(O)=C2C=3C(C(=O)N)=CC=CC=3NC2=C1CC1=CC=CN=C1 KHDBUZYUKAXECE-UHFFFAOYSA-N 0.000 claims description 2
• SKHRIGNKPWCVGR-UHFFFAOYSA-N 5-hydroxy-8-[(3-phenoxyphenyl)methyl]-9h-carbazole-4-carboxamide Chemical compound C1=CC(O)=C2C=3C(C(=O)N)=CC=CC=3NC2=C1CC(C=1)=CC=CC=1OC1=CC=CC=C1 SKHRIGNKPWCVGR-UHFFFAOYSA-N 0.000 claims description 2
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• RIOYVNUQLQDHMC-UHFFFAOYSA-N methyl 2-(9-benzyl-5-carbamoyl-2-phenylcarbazol-4-yl)oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC(C=3C=CC=CC=3)=CC=2N1CC1=CC=CC=C1 RIOYVNUQLQDHMC-UHFFFAOYSA-N 0.000 claims description 2
• XEGIWWBBRUTRBC-UHFFFAOYSA-N methyl 2-[9-benzyl-5-carbamoyl-2-(4-chlorophenyl)carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC(C=3C=CC(Cl)=CC=3)=CC=2N1CC1=CC=CC=C1 XEGIWWBBRUTRBC-UHFFFAOYSA-N 0.000 claims description 2
• KYNVMTIOCYUILP-UHFFFAOYSA-N methyl 5-hydroxy-8-[(2-methylphenyl)methyl]-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC=C1C KYNVMTIOCYUILP-UHFFFAOYSA-N 0.000 claims description 2
• JYKZPQXYQAZBDW-UHFFFAOYSA-N methyl 5-hydroxy-8-[(3-methylphenyl)methyl]-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC(C)=C1 JYKZPQXYQAZBDW-UHFFFAOYSA-N 0.000 claims description 2
• KXTFYUZQWPILHJ-UHFFFAOYSA-N methyl 5-oxo-7-phenyl-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1C(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2CC1C1=CC=CC=C1 KXTFYUZQWPILHJ-UHFFFAOYSA-N 0.000 claims description 2
• QMZHGZNTWCWPKL-UHFFFAOYSA-N methyl 5-oxo-8-(pyridin-2-ylmethyl)-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC=N1 QMZHGZNTWCWPKL-UHFFFAOYSA-N 0.000 claims description 2
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• GEZZVZOTGGOQOF-UHFFFAOYSA-N methyl 8-(cyclohexylmethyl)-5-hydroxy-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1CCCCC1 GEZZVZOTGGOQOF-UHFFFAOYSA-N 0.000 claims description 2
• HCKOATMSEPUWTK-UHFFFAOYSA-N methyl 8-(cyclohexylmethyl)-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1CCCCC1 HCKOATMSEPUWTK-UHFFFAOYSA-N 0.000 claims description 2
• KFDVBCLAXUUVGA-UHFFFAOYSA-N methyl 8-(naphthalen-1-ylmethyl)-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1=CC=C2C(CC3C=4NC=5C=CC=C(C=5C=4C(=O)CC3)C(=O)OC)=CC=CC2=C1 KFDVBCLAXUUVGA-UHFFFAOYSA-N 0.000 claims description 2
• QYLCAWWPPICHHY-UHFFFAOYSA-N methyl 8-[(2,3-difluorophenyl)methyl]-5-hydroxy-9H-carbazole-4-carboxylate Chemical compound FC1=C(C=CC=C1F)CC1=CC=C(C=2C3=C(C=CC=C3NC12)C(=O)OC)O QYLCAWWPPICHHY-UHFFFAOYSA-N 0.000 claims description 2
• ZRCUHIXGCNCATB-UHFFFAOYSA-N methyl 8-[(2-benzylphenyl)methyl]-5-hydroxy-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC=C1CC1=CC=CC=C1 ZRCUHIXGCNCATB-UHFFFAOYSA-N 0.000 claims description 2
• CMTJUHAPNXOKMH-UHFFFAOYSA-N methyl 8-[(2-chlorophenyl)methyl]-5-hydroxy-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC=C1Cl CMTJUHAPNXOKMH-UHFFFAOYSA-N 0.000 claims description 2
• QMOMLSDZBQSOKC-UHFFFAOYSA-N methyl 8-[(2-cyanophenyl)methyl]-5-hydroxy-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC=C1C#N QMOMLSDZBQSOKC-UHFFFAOYSA-N 0.000 claims description 2
• PJNHGSLSWGGCJL-UHFFFAOYSA-N methyl 8-[(2-cyanophenyl)methyl]-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC=C1C#N PJNHGSLSWGGCJL-UHFFFAOYSA-N 0.000 claims description 2
• HHQJXNGKINMDTB-UHFFFAOYSA-N methyl 8-[(2-methylphenyl)methyl]-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC=C1C HHQJXNGKINMDTB-UHFFFAOYSA-N 0.000 claims description 2
• MZRRZOWIEKWCDJ-UHFFFAOYSA-N methyl 8-[(3,5-dimethylphenyl)methyl]-5-hydroxy-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC(C)=CC(C)=C1 MZRRZOWIEKWCDJ-UHFFFAOYSA-N 0.000 claims description 2
• RWQODNUXKYOHEQ-UHFFFAOYSA-N methyl 8-[(3,5-dimethylphenyl)methyl]-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC(C)=CC(C)=C1 RWQODNUXKYOHEQ-UHFFFAOYSA-N 0.000 claims description 2
• QIBDGTAYYPRPBS-UHFFFAOYSA-N methyl 8-[(3-chlorophenyl)methyl]-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC(Cl)=C1 QIBDGTAYYPRPBS-UHFFFAOYSA-N 0.000 claims description 2
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• JTLVTCUZWKZOKJ-UHFFFAOYSA-N methyl 2-(9-benzyl-5-carbamoyl-1-chlorocarbazol-4-yl)oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=C(Cl)C=2N1CC1=CC=CC=C1 JTLVTCUZWKZOKJ-UHFFFAOYSA-N 0.000 claims 1
• PYPQRPRJXASPOF-UHFFFAOYSA-N methyl 2-[9-benzyl-5-carbamoyl-2-(furan-2-yl)carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC(C=3OC=CC=3)=CC=2N1CC1=CC=CC=C1 PYPQRPRJXASPOF-UHFFFAOYSA-N 0.000 claims 1
• IFEUCXUVVPNSIG-UHFFFAOYSA-N methyl 2-bromo-3-[(6-oxocyclohexen-1-yl)amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2C(CCCC=2)=O)=C1Br IFEUCXUVVPNSIG-UHFFFAOYSA-N 0.000 claims 1
• LDRKDSVFVSBAAT-UHFFFAOYSA-N methyl 2-chloro-3-[(6-oxocyclohexen-1-yl)amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2C(CCCC=2)=O)=C1Cl LDRKDSVFVSBAAT-UHFFFAOYSA-N 0.000 claims 1
• DRBWJKXGTZSNRR-UHFFFAOYSA-N methyl 5-hydroxy-8-(pyridin-2-ylmethyl)-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC=N1 DRBWJKXGTZSNRR-UHFFFAOYSA-N 0.000 claims 1
• OCPKAVXMHCEGPV-UHFFFAOYSA-N methyl 5-hydroxy-8-[(3-iodophenyl)methyl]-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC(I)=C1 OCPKAVXMHCEGPV-UHFFFAOYSA-N 0.000 claims 1
• NKUXPDUQKHJSPS-UHFFFAOYSA-N methyl 8-[(2,6-difluorophenyl)methyl]-5-hydroxy-9H-carbazole-4-carboxylate Chemical compound FC1=C(C(=CC=C1)F)CC1=CC=C(C=2C3=C(C=CC=C3NC12)C(=O)OC)O NKUXPDUQKHJSPS-UHFFFAOYSA-N 0.000 claims 1
• XCGUNJVHYPYOLO-UHFFFAOYSA-N methyl 8-[(2-chlorophenyl)methyl]-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC=C1Cl XCGUNJVHYPYOLO-UHFFFAOYSA-N 0.000 claims 1
• UBHOTNBNIBIRCF-UHFFFAOYSA-N methyl 8-benzyl-5-hydroxy-9H-carbazole-4-carboxylate Chemical compound COC(=O)c1cccc2[nH]c3c(Cc4ccccc4)ccc(O)c3c12 UBHOTNBNIBIRCF-UHFFFAOYSA-N 0.000 claims 1
• UUTJGUDEDSFFHG-UHFFFAOYSA-N methyl 8-benzyl-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC=C1 UUTJGUDEDSFFHG-UHFFFAOYSA-N 0.000 claims 1
• IMOVFZJGDDTZJA-UHFFFAOYSA-N methyl 9-benzyl-7-(furan-2-yl)-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC(C=3OC=CC=3)=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 IMOVFZJGDDTZJA-UHFFFAOYSA-N 0.000 claims 1
• 150000002923 oximes Chemical class 0.000 claims 1
• 230000001575 pathological effect Effects 0.000 claims 1
• 201000006292 polyarteritis nodosa Diseases 0.000 claims 1
• 238000012216 screening Methods 0.000 claims 1
• 230000001404 mediated effect Effects 0.000 abstract description 6
• 235000014113 dietary fatty acids Nutrition 0.000 abstract description 5
• 239000000194 fatty acid Substances 0.000 abstract description 5
• 229930195729 fatty acid Natural products 0.000 abstract description 5
• 150000004665 fatty acids Chemical class 0.000 abstract description 5
• 230000002401 inhibitory effect Effects 0.000 abstract description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 271
• 235000019439 ethyl acetate Nutrition 0.000 description 247
• 239000000203 mixture Substances 0.000 description 237
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 212
• 238000005160 1H NMR spectroscopy Methods 0.000 description 206
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 205
• 238000000921 elemental analysis Methods 0.000 description 199
• 239000000243 solution Substances 0.000 description 192
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 153
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 151
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• 239000007787 solid Substances 0.000 description 129
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• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 122
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 122
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 99
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 87
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 82
• 238000004440 column chromatography Methods 0.000 description 80
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 74
• 229910001868 water Inorganic materials 0.000 description 67
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 65
• 235000019341 magnesium sulphate Nutrition 0.000 description 65
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 59
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 58
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 53
• 239000011541 reaction mixture Substances 0.000 description 51
• 238000000034 method Methods 0.000 description 49
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• 239000012267 brine Substances 0.000 description 45
• 239000002904 solvent Substances 0.000 description 44
• 239000010410 layer Substances 0.000 description 43
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
• 238000006243 chemical reaction Methods 0.000 description 41
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 39
• 239000000284 extract Substances 0.000 description 38
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
• NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 35
• 238000001914 filtration Methods 0.000 description 35
• 229920006395 saturated elastomer Polymers 0.000 description 35
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 34
• 235000011114 ammonium hydroxide Nutrition 0.000 description 34
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
• 239000002244 precipitate Substances 0.000 description 32
• 239000000047 product Substances 0.000 description 32
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
• 239000000908 ammonium hydroxide Substances 0.000 description 31
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
• 229910000027 potassium carbonate Inorganic materials 0.000 description 30
• 229910000104 sodium hydride Inorganic materials 0.000 description 30
• YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 29
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• 239000000843 powder Substances 0.000 description 27
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 26
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• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 24
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• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• 238000002844 melting Methods 0.000 description 23
• 230000008018 melting Effects 0.000 description 23
• 239000003921 oil Substances 0.000 description 22
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 21
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
• 239000000543 intermediate Substances 0.000 description 19
• 229910052757 nitrogen Inorganic materials 0.000 description 18
• 239000007858 starting material Substances 0.000 description 18
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
• 239000006260 foam Substances 0.000 description 16
• 238000010992 reflux Methods 0.000 description 16
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Inorganic materials [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 16
• 239000000460 chlorine Substances 0.000 description 15
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• 238000003756 stirring Methods 0.000 description 15
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 14
• 239000003054 catalyst Substances 0.000 description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
• 125000000217 alkyl group Chemical group 0.000 description 13
• 239000011734 sodium Substances 0.000 description 13
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• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
• NIXWZYZFLFEHMB-UHFFFAOYSA-N methyl 3-amino-2-bromobenzoate Chemical compound COC(=O)C1=CC=CC(N)=C1Br NIXWZYZFLFEHMB-UHFFFAOYSA-N 0.000 description 12
• XKLNOVWDVMWTOB-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1h-carbazole Chemical class N1C2=CC=CC=C2C2=C1CCCC2 XKLNOVWDVMWTOB-UHFFFAOYSA-N 0.000 description 11
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 11
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
• 230000002452 interceptive effect Effects 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
• 238000005481 NMR spectroscopy Methods 0.000 description 10
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
• 150000005181 nitrobenzenes Chemical class 0.000 description 10
• 238000004809 thin layer chromatography Methods 0.000 description 10
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 10
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
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• 238000004587 chromatography analysis Methods 0.000 description 9
• 238000001704 evaporation Methods 0.000 description 9
• 230000008020 evaporation Effects 0.000 description 9
• 239000001257 hydrogen Substances 0.000 description 9
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• YUWPKYJCYRFBJT-UHFFFAOYSA-N methyl 2-bromo-3-nitrobenzoate Chemical compound COC(=O)C1=CC=CC([N+]([O-])=O)=C1Br YUWPKYJCYRFBJT-UHFFFAOYSA-N 0.000 description 9
• 239000000377 silicon dioxide Substances 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 8
• 238000002474 experimental method Methods 0.000 description 8
• 229910052736 halogen Inorganic materials 0.000 description 8
• 150000002367 halogens Chemical class 0.000 description 8
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• 125000006239 protecting group Chemical group 0.000 description 8
• 229910000029 sodium carbonate Inorganic materials 0.000 description 8
• 239000002168 alkylating agent Substances 0.000 description 7
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• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
• 229910000024 caesium carbonate Inorganic materials 0.000 description 7
• 238000001035 drying Methods 0.000 description 7
• 238000010828 elution Methods 0.000 description 7
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 7
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical group IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
• NKBQKMXNIWIFAE-UHFFFAOYSA-N methyl 3-amino-2-chlorobenzoate Chemical compound COC(=O)C1=CC=CC(N)=C1Cl NKBQKMXNIWIFAE-UHFFFAOYSA-N 0.000 description 7
• PSNSVDSRLUYDKF-UHFFFAOYSA-N methyl benzenesulfinate Chemical compound COS(=O)C1=CC=CC=C1 PSNSVDSRLUYDKF-UHFFFAOYSA-N 0.000 description 7
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
• 239000011591 potassium Substances 0.000 description 7
• BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 7
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 7
• IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 6
• 150000001350 alkyl halides Chemical class 0.000 description 6
• 229910021529 ammonia Inorganic materials 0.000 description 6
• YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 6
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 6
• 238000004519 manufacturing process Methods 0.000 description 6
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 6
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
• COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 6
• 239000011592 zinc chloride Substances 0.000 description 6
• 235000005074 zinc chloride Nutrition 0.000 description 6
• PATZGVUJUUNVJN-UHFFFAOYSA-N 2-[5-carbamoyl-9-(naphthalen-1-ylmethyl)carbazol-4-yl]oxyacetic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN1C2=CC=CC(OCC(O)=O)=C2C2=C1C=CC=C2C(=O)N PATZGVUJUUNVJN-UHFFFAOYSA-N 0.000 description 5
• HVKYETJTIUJSLB-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2-chlorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1Cl HVKYETJTIUJSLB-UHFFFAOYSA-N 0.000 description 5
• WTDJEGSXLFHZPY-UHFFFAOYSA-N 2-bromo-3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1Br WTDJEGSXLFHZPY-UHFFFAOYSA-N 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
• 230000003197 catalytic effect Effects 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• VKCMWLOBUILIOQ-UHFFFAOYSA-N ethyl 3-bromo-2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCCC(Br)C1=O VKCMWLOBUILIOQ-UHFFFAOYSA-N 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• JBCQPBVZKBEHNF-UHFFFAOYSA-N methyl 2-chloro-3-nitrobenzoate Chemical compound COC(=O)C1=CC=CC([N+]([O-])=O)=C1Cl JBCQPBVZKBEHNF-UHFFFAOYSA-N 0.000 description 5
• 239000012074 organic phase Substances 0.000 description 5
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
• 239000002002 slurry Substances 0.000 description 5
• 229940001593 sodium carbonate Drugs 0.000 description 5
• 235000017550 sodium carbonate Nutrition 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 235000009518 sodium iodide Nutrition 0.000 description 5
• HCQNYAIKYZCDBC-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-2-propan-2-ylcarbazol-4-yl)oxyacetic acid Chemical compound C=1C(C(C)C)=CC(OCC(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 HCQNYAIKYZCDBC-UHFFFAOYSA-N 0.000 description 4
• BLCNILYGCATZEH-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(2,3-difluorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(F)=C1F BLCNILYGCATZEH-UHFFFAOYSA-N 0.000 description 4
• FJGZTTJYTQDFHV-UHFFFAOYSA-N 9-benzyl-5-hydroxycarbazole-4-carboxamide Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1 FJGZTTJYTQDFHV-UHFFFAOYSA-N 0.000 description 4
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
• 101150041968 CDC13 gene Proteins 0.000 description 4
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• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
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• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
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• UIMGRPXPFBJHJJ-UHFFFAOYSA-N 2-[5-carbamoyl-9-[(3-chlorophenyl)methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(Cl)=C1 UIMGRPXPFBJHJJ-UHFFFAOYSA-N 0.000 description 3
• GCOWGWQVPARYNI-UHFFFAOYSA-N 2-[5-carbamoyl-9-[[3-(trifluoromethoxy)phenyl]methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(OC(F)(F)F)=C1 GCOWGWQVPARYNI-UHFFFAOYSA-N 0.000 description 3
• NDTBXYQGBBMXLW-UHFFFAOYSA-N 2-[5-carbamoyl-9-[[3-(trifluoromethyl)phenyl]methyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(C(F)(F)F)=C1 NDTBXYQGBBMXLW-UHFFFAOYSA-N 0.000 description 3
• XERTWWFWTYYSOP-UHFFFAOYSA-N 2-[9-benzyl-5-carbamoyl-2-(4-chlorophenyl)carbazol-4-yl]oxyacetic acid Chemical compound C12=CC(C=3C=CC(Cl)=CC=3)=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1 XERTWWFWTYYSOP-UHFFFAOYSA-N 0.000 description 3
• JTWGFKHCAPESJY-UHFFFAOYSA-N 2-[9-benzyl-5-carbamoyl-2-(furan-2-yl)carbazol-4-yl]oxyacetic acid Chemical compound C12=CC(C=3OC=CC=3)=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1 JTWGFKHCAPESJY-UHFFFAOYSA-N 0.000 description 3
• WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 3
• VXCYQLJSFFVGMX-UHFFFAOYSA-N 5-hydroxy-9-[(3-phenoxyphenyl)methyl]carbazole-4-carboxamide Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC(C=1)=CC=CC=1OC1=CC=CC=C1 VXCYQLJSFFVGMX-UHFFFAOYSA-N 0.000 description 3
• GLUGRMILFITQLF-UHFFFAOYSA-N 5-hydroxy-9-[[3-(trifluoromethoxy)phenyl]methyl]carbazole-4-carboxamide Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(OC(F)(F)F)=C1 GLUGRMILFITQLF-UHFFFAOYSA-N 0.000 description 3
• GBTJVHADNGRQBQ-UHFFFAOYSA-N 5-methoxy-8-methyl-9h-carbazole-4-carboxamide Chemical compound N1C2=CC=CC(C(N)=O)=C2C2=C1C(C)=CC=C2OC GBTJVHADNGRQBQ-UHFFFAOYSA-N 0.000 description 3
• ZQBMPCCWRBCRQX-UHFFFAOYSA-N 9-[(2,3-difluorophenyl)methyl]-5-hydroxycarbazole-4-carboxamide Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(F)=C1F ZQBMPCCWRBCRQX-UHFFFAOYSA-N 0.000 description 3
• IULCUUPYAJAXDL-UHFFFAOYSA-N 9-[(2,6-difluorophenyl)methyl]-5-hydroxycarbazole-4-carboxamide Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=C(F)C=CC=C1F IULCUUPYAJAXDL-UHFFFAOYSA-N 0.000 description 3
• JRWSMGTUZSZVEN-UHFFFAOYSA-N 9-[(2-benzylphenyl)methyl]-5-hydroxycarbazole-4-carboxamide Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1CC1=CC=CC=C1 JRWSMGTUZSZVEN-UHFFFAOYSA-N 0.000 description 3
• SRAJNLCQHFQSIZ-UHFFFAOYSA-N 9-[(2-fluorophenyl)methyl]-5-hydroxycarbazole-4-carboxamide Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1F SRAJNLCQHFQSIZ-UHFFFAOYSA-N 0.000 description 3
• SSKLUMQEAPFGGT-UHFFFAOYSA-N 9-benzyl-5-methoxy-8-methyl-1,2,3,4-tetrahydrocarbazole-4-carboxamide Chemical compound C1=2CCCC(C(N)=O)C=2C=2C(OC)=CC=C(C)C=2N1CC1=CC=CC=C1 SSKLUMQEAPFGGT-UHFFFAOYSA-N 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 229940114079 arachidonic acid Drugs 0.000 description 3
• 235000021342 arachidonic acid Nutrition 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
• 150000007942 carboxylates Chemical class 0.000 description 3
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 230000020335 dealkylation Effects 0.000 description 3
• 238000006900 dealkylation reaction Methods 0.000 description 3
• 150000002085 enols Chemical class 0.000 description 3
• 125000004494 ethyl ester group Chemical group 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 229910052808 lithium carbonate Inorganic materials 0.000 description 3
• PCVLMLMVJMGCJV-UHFFFAOYSA-N methyl 5-hydroxy-9-(pyridin-2-ylmethyl)carbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=N1 PCVLMLMVJMGCJV-UHFFFAOYSA-N 0.000 description 3
• TWOPOKNACRNJDU-UHFFFAOYSA-N methyl 5-hydroxy-9-[(3-iodophenyl)methyl]carbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(I)=C1 TWOPOKNACRNJDU-UHFFFAOYSA-N 0.000 description 3
• UNVNCIUTBUGNTR-UHFFFAOYSA-N methyl 5-hydroxy-9-[[2-(trifluoromethyl)phenyl]methyl]carbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1C(F)(F)F UNVNCIUTBUGNTR-UHFFFAOYSA-N 0.000 description 3
• QOPNWBDBQJGPAE-UHFFFAOYSA-N methyl 5-hydroxy-9-[[3-(trifluoromethyl)phenyl]methyl]carbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(C(F)(F)F)=C1 QOPNWBDBQJGPAE-UHFFFAOYSA-N 0.000 description 3
• MRQKZMCJLKMCJL-UHFFFAOYSA-N methyl 9-[(2,6-difluorophenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=C(F)C=CC=C1F MRQKZMCJLKMCJL-UHFFFAOYSA-N 0.000 description 3
• XTYILSXHCGTKHW-UHFFFAOYSA-N methyl 9-[(2-chlorophenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1Cl XTYILSXHCGTKHW-UHFFFAOYSA-N 0.000 description 3
• FIORTLXKZVVDKE-UHFFFAOYSA-N methyl 9-[(2-cyanophenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1C#N FIORTLXKZVVDKE-UHFFFAOYSA-N 0.000 description 3
• ZFFJJZQSUVMMOI-UHFFFAOYSA-N methyl 9-[(2-fluorophenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1F ZFFJJZQSUVMMOI-UHFFFAOYSA-N 0.000 description 3
• KYSDGKPVRQSADQ-UHFFFAOYSA-N methyl 9-[(3,5-dimethylphenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC(C)=CC(C)=C1 KYSDGKPVRQSADQ-UHFFFAOYSA-N 0.000 description 3
• OEGIIJDSTAEKEM-UHFFFAOYSA-N methyl 9-[(3-cyanophenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(C#N)=C1 OEGIIJDSTAEKEM-UHFFFAOYSA-N 0.000 description 3
• GGSHGRAQDSJBOY-UHFFFAOYSA-N methyl 9-[(3-fluorophenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(F)=C1 GGSHGRAQDSJBOY-UHFFFAOYSA-N 0.000 description 3
• 239000012299 nitrogen atmosphere Substances 0.000 description 3
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• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 3
• 238000001665 trituration Methods 0.000 description 3
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• BGMMWAHLBZGOBB-UHFFFAOYSA-N (2-chloro-4-fluoro-5-nitrophenyl) ethyl carbonate Chemical compound CCOC(=O)OC1=CC([N+]([O-])=O)=C(F)C=C1Cl BGMMWAHLBZGOBB-UHFFFAOYSA-N 0.000 description 2
• YQKSSJXIMXARGI-UHFFFAOYSA-N (2-chloro-4-fluorophenyl) ethyl carbonate Chemical compound CCOC(=O)OC1=CC=C(F)C=C1Cl YQKSSJXIMXARGI-UHFFFAOYSA-N 0.000 description 2
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
• QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
• FWLWTILKTABGKQ-UHFFFAOYSA-N 1-(bromomethyl)-3-methylbenzene Chemical compound CC1=CC=CC(CBr)=C1 FWLWTILKTABGKQ-UHFFFAOYSA-N 0.000 description 2
• CRONHBXGPYQWHX-UHFFFAOYSA-N 1-chloro-5-fluoro-2-methoxy-4-nitrobenzene Chemical compound COC1=CC([N+]([O-])=O)=C(F)C=C1Cl CRONHBXGPYQWHX-UHFFFAOYSA-N 0.000 description 2
• RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 2
• XMNFDVRHTKIVQK-UHFFFAOYSA-N 2-(9-benzyl-5-carbamoyl-2-methoxycarbazol-4-yl)oxyacetic acid Chemical compound C=1C(OC)=CC(OCC(O)=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 XMNFDVRHTKIVQK-UHFFFAOYSA-N 0.000 description 2
• JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 2
• FZCVOGNJZMDIQT-UHFFFAOYSA-N 2-[9-benzyl-5-carbamoyl-2-[4-(trifluoromethyl)phenyl]carbazol-4-yl]oxyacetic acid Chemical compound C12=CC(C=3C=CC(=CC=3)C(F)(F)F)=CC(OCC(O)=O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1 FZCVOGNJZMDIQT-UHFFFAOYSA-N 0.000 description 2
• RUTKJXMYXZFXPQ-UHFFFAOYSA-N 2-fluoro-5-methoxyaniline Chemical class COC1=CC=C(F)C(N)=C1 RUTKJXMYXZFXPQ-UHFFFAOYSA-N 0.000 description 2
• FBELQXBIHJGQRS-UHFFFAOYSA-N 5-hydroxy-7-methyl-9-[(3-methylphenyl)methyl]carbazole-4-carboxamide Chemical compound CC1=CC=CC(CN2C3=CC(C)=CC(O)=C3C3=C(C(N)=O)C=CC=C32)=C1 FBELQXBIHJGQRS-UHFFFAOYSA-N 0.000 description 2
• RUEFNDMBRXTRPS-UHFFFAOYSA-N 5-hydroxy-9-(pyridin-3-ylmethyl)carbazole-4-carboxamide Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CN=C1 RUEFNDMBRXTRPS-UHFFFAOYSA-N 0.000 description 2
• GIJITUQEJWSBRI-UHFFFAOYSA-N 5-hydroxy-9-[(2-methylphenyl)methyl]carbazole-4-carboxamide Chemical compound CC1=CC=CC=C1CN1C2=CC=CC(C(N)=O)=C2C2=C(O)C=CC=C21 GIJITUQEJWSBRI-UHFFFAOYSA-N 0.000 description 2
• SFVXFRXONWSBOB-UHFFFAOYSA-N 5-hydroxy-9-[(3-iodophenyl)methyl]carbazole-4-carboxamide Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC(I)=C1 SFVXFRXONWSBOB-UHFFFAOYSA-N 0.000 description 2
• KQXAXQGJCMZYBA-UHFFFAOYSA-N 5-hydroxy-9-[(3-methylphenyl)methyl]carbazole-4-carboxamide Chemical compound CC1=CC=CC(CN2C3=CC=CC(=C3C3=C(O)C=CC=C32)C(N)=O)=C1 KQXAXQGJCMZYBA-UHFFFAOYSA-N 0.000 description 2
• MSRUWXVJOFPJQK-UHFFFAOYSA-N 5-hydroxy-9-[[2-(trifluoromethyl)phenyl]methyl]carbazole-4-carboxamide Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)N)=CC=CC=2N1CC1=CC=CC=C1C(F)(F)F MSRUWXVJOFPJQK-UHFFFAOYSA-N 0.000 description 2
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• 241000124008 Mammalia Species 0.000 description 2
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• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
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• 238000007126 N-alkylation reaction Methods 0.000 description 2
• 238000010934 O-alkylation reaction Methods 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• 229910000564 Raney nickel Inorganic materials 0.000 description 2
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
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• 235000019257 ammonium acetate Nutrition 0.000 description 2
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• 150000003863 ammonium salts Chemical class 0.000 description 2
• 239000000538 analytical sample Substances 0.000 description 2
• 239000000010 aprotic solvent Substances 0.000 description 2
• 150000001502 aryl halides Chemical class 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
• 244000309464 bull Species 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 150000003983 crown ethers Chemical class 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 description 2
• 239000012380 dealkylating agent Substances 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 238000004821 distillation Methods 0.000 description 2
• 230000032050 esterification Effects 0.000 description 2
• 238000005886 esterification reaction Methods 0.000 description 2
• DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
• NTTXCAMHFZZOTH-UHFFFAOYSA-N ethyl 5-methoxy-8-methyl-2,3,4,9-tetrahydro-1h-carbazole-4-carboxylate Chemical compound N1C2=C(C)C=CC(OC)=C2C2=C1CCCC2C(=O)OCC NTTXCAMHFZZOTH-UHFFFAOYSA-N 0.000 description 2
• AANXBKIMDTVFQA-UHFFFAOYSA-N ethyl 9-benzyl-8-chloro-5-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxylate Chemical compound CCOC(=O)C1CCCC2=C1C1=C(OC)C=CC(Cl)=C1N2CC1=CC=CC=C1 AANXBKIMDTVFQA-UHFFFAOYSA-N 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 239000013067 intermediate product Substances 0.000 description 2
• 229910052740 iodine Chemical group 0.000 description 2
• 239000012280 lithium aluminium hydride Substances 0.000 description 2
• 229910000103 lithium hydride Inorganic materials 0.000 description 2
• HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
• KDHXHMORUAHVQC-UHFFFAOYSA-M lithium;2-[9-benzyl-5-carbamoyl-2-[tri(propan-2-yl)silyloxymethyl]carbazol-4-yl]oxyacetate Chemical compound [Li+].C=1C(CO[Si](C(C)C)(C(C)C)C(C)C)=CC(OCC([O-])=O)=C(C2=C(C(N)=O)C=CC=C22)C=1N2CC1=CC=CC=C1 KDHXHMORUAHVQC-UHFFFAOYSA-M 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• QAGFBWORHHSDLU-UHFFFAOYSA-N methyl 2-(9-benzyl-5-carbamoyl-2-methylcarbazol-4-yl)oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC(C)=CC=2N1CC1=CC=CC=C1 QAGFBWORHHSDLU-UHFFFAOYSA-N 0.000 description 2
• VYJSSWLKFMVSKB-UHFFFAOYSA-N methyl 2-(9-benzyl-5-carbamoylcarbazol-4-yl)oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 VYJSSWLKFMVSKB-UHFFFAOYSA-N 0.000 description 2
• ADHVHSIJKWWKPA-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[(2-fluorophenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC=C1F ADHVHSIJKWWKPA-UHFFFAOYSA-N 0.000 description 2
• CLVREPBFXISVON-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[(3,5-dimethylphenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC(C)=CC(C)=C1 CLVREPBFXISVON-UHFFFAOYSA-N 0.000 description 2
• CHNIRPZCTJAGDW-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[(3-iodophenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC(I)=C1 CHNIRPZCTJAGDW-UHFFFAOYSA-N 0.000 description 2
• HBLWDERQOAUKGN-UHFFFAOYSA-N methyl 2-bromo-3-[(5-methyl-3-oxocyclohexen-1-yl)amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2CC(C)CC(=O)C=2)=C1Br HBLWDERQOAUKGN-UHFFFAOYSA-N 0.000 description 2
• LHOAGMPBVLOYLJ-UHFFFAOYSA-N methyl 2-bromo-3-[[3-oxo-5-[4-(trifluoromethyl)phenyl]cyclohexen-1-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2CC(CC(=O)C=2)C=2C=CC(=CC=2)C(F)(F)F)=C1Br LHOAGMPBVLOYLJ-UHFFFAOYSA-N 0.000 description 2
• PFNZJCITVCCGNP-UHFFFAOYSA-N methyl 5-hydroxy-7-methyl-9-[(3-methylphenyl)methyl]carbazole-4-carboxylate Chemical compound C12=CC(C)=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(C)=C1 PFNZJCITVCCGNP-UHFFFAOYSA-N 0.000 description 2
• DEJNWOYTOSFGQM-UHFFFAOYSA-N methyl 5-hydroxy-9-(naphthalen-1-ylmethyl)carbazole-4-carboxylate Chemical compound C=1C=CC2=CC=CC=C2C=1CN1C2=CC=CC(O)=C2C2=C1C=CC=C2C(=O)OC DEJNWOYTOSFGQM-UHFFFAOYSA-N 0.000 description 2
• YIEMRYNGKWONSK-UHFFFAOYSA-N methyl 5-hydroxy-9-(pyridin-3-ylmethyl)carbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CN=C1 YIEMRYNGKWONSK-UHFFFAOYSA-N 0.000 description 2
• DWIAYAAEVRBFGW-UHFFFAOYSA-N methyl 5-hydroxy-9-[(2-methylphenyl)methyl]carbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1C DWIAYAAEVRBFGW-UHFFFAOYSA-N 0.000 description 2
• ZLSAMYFQRGMPFY-UHFFFAOYSA-N methyl 5-hydroxy-9-[(3-methylphenyl)methyl]carbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(C)=C1 ZLSAMYFQRGMPFY-UHFFFAOYSA-N 0.000 description 2
• ZEMCNOHCNUFOAM-UHFFFAOYSA-N methyl 5-hydroxy-9-[(3-phenoxyphenyl)methyl]carbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC(C=1)=CC=CC=1OC1=CC=CC=C1 ZEMCNOHCNUFOAM-UHFFFAOYSA-N 0.000 description 2
• LPGOWPXYSCNOID-UHFFFAOYSA-N methyl 5-hydroxy-9-[[3-(trifluoromethoxy)phenyl]methyl]carbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(OC(F)(F)F)=C1 LPGOWPXYSCNOID-UHFFFAOYSA-N 0.000 description 2
• XCBKEVAXNVDHMT-UHFFFAOYSA-N methyl 5-hydroxy-9H-carbazole-4-carboxylate Chemical compound OC1=CC=CC=2NC3=CC=CC(=C3C1=2)C(=O)OC XCBKEVAXNVDHMT-UHFFFAOYSA-N 0.000 description 2
• WAUGXTPQYOKHNZ-UHFFFAOYSA-N methyl 5-oxo-7-pentyl-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound N1C2=CC=CC(C(=O)OC)=C2C2=C1CC(CCCCC)CC2=O WAUGXTPQYOKHNZ-UHFFFAOYSA-N 0.000 description 2
• YDTQOOFEQXDLDW-UHFFFAOYSA-N methyl 5-oxo-7-propan-2-yl-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1C(C(C)C)CC(=O)C2=C1NC1=C2C(C(=O)OC)=CC=C1 YDTQOOFEQXDLDW-UHFFFAOYSA-N 0.000 description 2
• YBGBXOFBYJAQNA-UHFFFAOYSA-N methyl 5-oxo-9-(pyridin-2-ylmethyl)-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=N1 YBGBXOFBYJAQNA-UHFFFAOYSA-N 0.000 description 2
• MYCRKMVCEFJGCB-UHFFFAOYSA-N methyl 5-oxo-9-(pyridin-3-ylmethyl)-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CN=C1 MYCRKMVCEFJGCB-UHFFFAOYSA-N 0.000 description 2
• YTCCWBPOFPFFCR-UHFFFAOYSA-N methyl 5-oxo-9-[(3-phenoxyphenyl)methyl]-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC(C=1)=CC=CC=1OC1=CC=CC=C1 YTCCWBPOFPFFCR-UHFFFAOYSA-N 0.000 description 2
• PEPCSOVPNMWRKL-UHFFFAOYSA-N methyl 5-oxo-9-[[3-(trifluoromethyl)phenyl]methyl]-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(C(F)(F)F)=C1 PEPCSOVPNMWRKL-UHFFFAOYSA-N 0.000 description 2
• LQLQHQVSCDFJIP-UHFFFAOYSA-N methyl 7-methyl-9-[(3-methylphenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CC(C)CC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(C)=C1 LQLQHQVSCDFJIP-UHFFFAOYSA-N 0.000 description 2
• HZLCOQKRNRZMBL-UHFFFAOYSA-N methyl 9-(naphthalen-1-ylmethyl)-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1CCC(=O)C2=C1N(CC=1C3=CC=CC=C3C=CC=1)C1=C2C(C(=O)OC)=CC=C1 HZLCOQKRNRZMBL-UHFFFAOYSA-N 0.000 description 2
• FFJIJEXTIQAHDU-UHFFFAOYSA-N methyl 9-[(2,3-difluorophenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(F)=C1F FFJIJEXTIQAHDU-UHFFFAOYSA-N 0.000 description 2
• NZRDUNGWEBSXKX-UHFFFAOYSA-N methyl 9-[(2,3-difluorophenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(F)=C1F NZRDUNGWEBSXKX-UHFFFAOYSA-N 0.000 description 2
• MQNNUYXCYBUUPW-UHFFFAOYSA-N methyl 9-[(2,6-dichlorophenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=C(Cl)C=CC=C1Cl MQNNUYXCYBUUPW-UHFFFAOYSA-N 0.000 description 2
• RMDLRBVVUSFDPK-UHFFFAOYSA-N methyl 9-[(2-benzylphenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1CC1=CC=CC=C1 RMDLRBVVUSFDPK-UHFFFAOYSA-N 0.000 description 2
• GSKCQVFTFZVUDE-UHFFFAOYSA-N methyl 9-[(2-benzylphenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1CC1=CC=CC=C1 GSKCQVFTFZVUDE-UHFFFAOYSA-N 0.000 description 2
• ZYVPKFGMYOFKST-UHFFFAOYSA-N methyl 9-[(2-chlorophenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1Cl ZYVPKFGMYOFKST-UHFFFAOYSA-N 0.000 description 2
• HIEJYFQOXJHYHA-UHFFFAOYSA-N methyl 9-[(2-cyanophenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1C#N HIEJYFQOXJHYHA-UHFFFAOYSA-N 0.000 description 2
• XFHQZLZSUZCKLV-UHFFFAOYSA-N methyl 9-[(2-fluorophenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1F XFHQZLZSUZCKLV-UHFFFAOYSA-N 0.000 description 2
• QLXRVTDGPVGHFD-UHFFFAOYSA-N methyl 9-[(3-chlorophenyl)methyl]-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(Cl)=C1 QLXRVTDGPVGHFD-UHFFFAOYSA-N 0.000 description 2
• RMSKZGQSHDPGNL-UHFFFAOYSA-N methyl 9-[(3-chlorophenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(Cl)=C1 RMSKZGQSHDPGNL-UHFFFAOYSA-N 0.000 description 2
• UXAWWFVDQJYGDY-UHFFFAOYSA-N methyl 9-[(3-cyanophenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(C#N)=C1 UXAWWFVDQJYGDY-UHFFFAOYSA-N 0.000 description 2
• SNOCNJSDASZTKU-UHFFFAOYSA-N methyl 9-[(3-fluorophenyl)methyl]-5-hydroxy-7-methylcarbazole-4-carboxylate Chemical compound C12=CC(C)=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(F)=C1 SNOCNJSDASZTKU-UHFFFAOYSA-N 0.000 description 2
• JSOLWPACLIOTBG-UHFFFAOYSA-N methyl 9-[(3-fluorophenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(F)=C1 JSOLWPACLIOTBG-UHFFFAOYSA-N 0.000 description 2
• HBLQCKSZNTXTII-UHFFFAOYSA-N methyl 9-[(3-fluorophenyl)methyl]-7-methyl-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CC(C)CC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(F)=C1 HBLQCKSZNTXTII-UHFFFAOYSA-N 0.000 description 2
• GKCQFBAIJMCCKA-UHFFFAOYSA-N methyl 9-[(3-iodophenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(I)=C1 GKCQFBAIJMCCKA-UHFFFAOYSA-N 0.000 description 2
• HXURTMLFEIDBBQ-UHFFFAOYSA-N methyl 9-[(3-methylphenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(C)=C1 HXURTMLFEIDBBQ-UHFFFAOYSA-N 0.000 description 2
• GSSRRPUGXNPLSG-UHFFFAOYSA-N methyl 9-benzyl-5-hydroxy-7-methylcarbazole-4-carboxylate Chemical compound C12=CC(C)=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 GSSRRPUGXNPLSG-UHFFFAOYSA-N 0.000 description 2
• LRAQLBIAAGYKIS-UHFFFAOYSA-N methyl 9-benzyl-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 LRAQLBIAAGYKIS-UHFFFAOYSA-N 0.000 description 2
• OAKDTHHXAYPQFO-UHFFFAOYSA-N methyl 9-benzyl-5-oxo-7-propan-2-yl-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CC(C(C)C)CC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 OAKDTHHXAYPQFO-UHFFFAOYSA-N 0.000 description 2
• VWBPDQQZNOYORV-UHFFFAOYSA-N methyl 9-benzyl-7-(4-chlorophenyl)-5-hydroxycarbazole-4-carboxylate Chemical compound C12=CC(C=3C=CC(Cl)=CC=3)=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 VWBPDQQZNOYORV-UHFFFAOYSA-N 0.000 description 2
• RACLAUSVCLNLIZ-UHFFFAOYSA-N methyl 9-benzyl-7-(4-chlorophenyl)-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CC(C=3C=CC(Cl)=CC=3)CC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 RACLAUSVCLNLIZ-UHFFFAOYSA-N 0.000 description 2
• JVHMDDPXQAAJIT-UHFFFAOYSA-N methyl 9-benzyl-7-methyl-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CC(C)CC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 JVHMDDPXQAAJIT-UHFFFAOYSA-N 0.000 description 2
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• 239000003960 organic solvent Substances 0.000 description 2
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• SDXJUKFDGCMOHO-UHFFFAOYSA-N methyl 2-(9-benzyl-5-carbamoyl-2-methoxycarbazol-4-yl)oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC(OC)=CC=2N1CC1=CC=CC=C1 SDXJUKFDGCMOHO-UHFFFAOYSA-N 0.000 description 1
• YSCQNQWTIHYXKX-UHFFFAOYSA-N methyl 2-[(5-carbamoyl-1-chloro-9h-carbazol-4-yl)oxy]acetate Chemical compound N1C2=CC=CC(C(N)=O)=C2C2=C1C(Cl)=CC=C2OCC(=O)OC YSCQNQWTIHYXKX-UHFFFAOYSA-N 0.000 description 1
• ANUWEGZYNYTFIU-UHFFFAOYSA-N methyl 2-[(9-benzyl-5-carbamoyl-1-fluoro-5,6,7,8-tetrahydrocarbazol-4-yl)oxy]acetate Chemical compound C1=2CCCC(C(N)=O)C=2C=2C(OCC(=O)OC)=CC=C(F)C=2N1CC1=CC=CC=C1 ANUWEGZYNYTFIU-UHFFFAOYSA-N 0.000 description 1
• CKSUTZMEGFFIEN-UHFFFAOYSA-N methyl 2-[(9-benzyl-5-carbamoyl-1-methyl-5,6,7,8-tetrahydrocarbazol-4-yl)oxy]acetate Chemical compound C1=2CCCC(C(N)=O)C=2C=2C(OCC(=O)OC)=CC=C(C)C=2N1CC1=CC=CC=C1 CKSUTZMEGFFIEN-UHFFFAOYSA-N 0.000 description 1
• FNUZWKBIAREHLD-UHFFFAOYSA-N methyl 2-[5-carbamoyl-2-methyl-9-[(3-methylphenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC(C)=CC=2N1CC1=CC=CC(C)=C1 FNUZWKBIAREHLD-UHFFFAOYSA-N 0.000 description 1
• NFMFPZIANORNMT-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-(naphthalen-1-ylmethyl)carbazol-4-yl]oxyacetate Chemical compound C=1C=CC2=CC=CC=C2C=1CN1C2=CC=CC(C(N)=O)=C2C2=C1C=CC=C2OCC(=O)OC NFMFPZIANORNMT-UHFFFAOYSA-N 0.000 description 1
• QFOIAPZFZSIQQU-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-(pyridin-2-ylmethyl)carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC=N1 QFOIAPZFZSIQQU-UHFFFAOYSA-N 0.000 description 1
• FXPAYFUKFKKWTE-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-(pyridin-3-ylmethyl)carbazol-4-yl]oxyacetate Chemical compound COC(=O)COC1=CC=CC2=C1C3=C(C=CC=C3N2CC4=CN=CC=C4)C(=O)N FXPAYFUKFKKWTE-UHFFFAOYSA-N 0.000 description 1
• LCJOXWCQHMXHCK-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[(2,3-difluorophenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC(F)=C1F LCJOXWCQHMXHCK-UHFFFAOYSA-N 0.000 description 1
• OSDNLLDSSFQISV-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[(2,6-difluorophenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=C(F)C=CC=C1F OSDNLLDSSFQISV-UHFFFAOYSA-N 0.000 description 1
• HKHJMXGFWWRYGH-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[(2-cyanophenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC=C1C#N HKHJMXGFWWRYGH-UHFFFAOYSA-N 0.000 description 1
• XHDSTXFXSCWLSF-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[(2-methylphenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC=C1C XHDSTXFXSCWLSF-UHFFFAOYSA-N 0.000 description 1
• RKFXVRCQRMCWKM-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[(3-fluorophenyl)methyl]-2-methylcarbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC(C)=CC=2N1CC1=CC=CC(F)=C1 RKFXVRCQRMCWKM-UHFFFAOYSA-N 0.000 description 1
• DQVRYWNGCRCKPY-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[(3-methylphenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC(C)=C1 DQVRYWNGCRCKPY-UHFFFAOYSA-N 0.000 description 1
• PWRRXYOCPPBGMV-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[[2-(trifluoromethyl)phenyl]methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC=C1C(F)(F)F PWRRXYOCPPBGMV-UHFFFAOYSA-N 0.000 description 1
• GBNZDHSCUSOAFU-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[[3-(trifluoromethoxy)phenyl]methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC(OC(F)(F)F)=C1 GBNZDHSCUSOAFU-UHFFFAOYSA-N 0.000 description 1
• PENJYQTYSNGYMY-UHFFFAOYSA-N methyl 2-[5-carbamoyl-9-[[3-(trifluoromethyl)phenyl]methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC(C(F)(F)F)=C1 PENJYQTYSNGYMY-UHFFFAOYSA-N 0.000 description 1
• SUUPRIMFSCSGTM-UHFFFAOYSA-N methyl 2-[9-[(2-benzylphenyl)methyl]-5-carbamoylcarbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC=CC=2N1CC1=CC=CC=C1CC1=CC=CC=C1 SUUPRIMFSCSGTM-UHFFFAOYSA-N 0.000 description 1
• RYAXFUQTWZDWQK-UHFFFAOYSA-N methyl 2-[9-benzyl-5-carbamoyl-2-[4-(trifluoromethyl)phenyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC)=CC(C=3C=CC(=CC=3)C(F)(F)F)=CC=2N1CC1=CC=CC=C1 RYAXFUQTWZDWQK-UHFFFAOYSA-N 0.000 description 1
• NFZUELIAEKCBJM-UHFFFAOYSA-N methyl 2-bromo-3-[(3-oxo-5-pentylcyclohexen-1-yl)amino]benzoate Chemical compound C1C(CCCCC)CC(=O)C=C1NC1=CC=CC(C(=O)OC)=C1Br NFZUELIAEKCBJM-UHFFFAOYSA-N 0.000 description 1
• PQWZEKJCTAZIQS-UHFFFAOYSA-N methyl 2-bromo-3-[(3-oxo-5-phenylcyclohexen-1-yl)amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2CC(CC(=O)C=2)C=2C=CC=CC=2)=C1Br PQWZEKJCTAZIQS-UHFFFAOYSA-N 0.000 description 1
• REGWHUMRLZDXMW-UHFFFAOYSA-N methyl 2-bromo-3-[(3-oxo-5-propan-2-ylcyclohexen-1-yl)amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2CC(CC(=O)C=2)C(C)C)=C1Br REGWHUMRLZDXMW-UHFFFAOYSA-N 0.000 description 1
• PPUUXYOKSGMPNS-UHFFFAOYSA-N methyl 2-bromo-3-[(6-oxo-4-propan-2-ylcyclohexen-1-yl)amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2C(CC(CC=2)C(C)C)=O)=C1Br PPUUXYOKSGMPNS-UHFFFAOYSA-N 0.000 description 1
• JWLWCBBXKQCPJI-UHFFFAOYSA-N methyl 2-bromo-3-[[4-(4-chlorophenyl)-6-oxocyclohexen-1-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2C(CC(CC=2)C=2C=CC(Cl)=CC=2)=O)=C1Br JWLWCBBXKQCPJI-UHFFFAOYSA-N 0.000 description 1
• MDWRQJKKKDNNLG-UHFFFAOYSA-N methyl 2-bromo-3-[[4-(hydroxymethyl)-6-oxocyclohexen-1-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2C(CC(CO)CC=2)=O)=C1Br MDWRQJKKKDNNLG-UHFFFAOYSA-N 0.000 description 1
• SRUQBVOXRAGPPX-UHFFFAOYSA-N methyl 2-bromo-3-[[5-(4-chlorophenyl)-3-oxocyclohexen-1-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2CC(CC(=O)C=2)C=2C=CC(Cl)=CC=2)=C1Br SRUQBVOXRAGPPX-UHFFFAOYSA-N 0.000 description 1
• ZJJOZUABJIVBLZ-UHFFFAOYSA-N methyl 2-bromo-3-[[5-(hydroxymethyl)-3-oxocyclohexen-1-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2CC(CO)CC(=O)C=2)=C1Br ZJJOZUABJIVBLZ-UHFFFAOYSA-N 0.000 description 1
• UOLTZUXIPBZKOS-UHFFFAOYSA-N methyl 5-bromo-5-nitrocyclohexa-1,3-diene-1-carboxylate Chemical compound COC(C=1CC(C=CC=1)([N+](=O)[O-])Br)=O UOLTZUXIPBZKOS-UHFFFAOYSA-N 0.000 description 1
• LGXOONHKKWGSAJ-UHFFFAOYSA-N methyl 5-hydroxy-7-methyl-8-[(3-methylphenyl)methyl]-9h-carbazole-4-carboxylate Chemical compound CC1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC(C)=C1 LGXOONHKKWGSAJ-UHFFFAOYSA-N 0.000 description 1
• XDKCFHNIBOULLE-UHFFFAOYSA-N methyl 5-hydroxy-8-(naphthalen-1-ylmethyl)-9h-carbazole-4-carboxylate Chemical compound C1=CC=C2C(CC3=C4NC=5C=CC=C(C=5C4=C(O)C=C3)C(=O)OC)=CC=CC2=C1 XDKCFHNIBOULLE-UHFFFAOYSA-N 0.000 description 1
• MJMQBPVZKYFGNI-UHFFFAOYSA-N methyl 5-hydroxy-8-(pyridin-3-ylmethyl)-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CN=C1 MJMQBPVZKYFGNI-UHFFFAOYSA-N 0.000 description 1
• NFKZUNBTGGOYET-UHFFFAOYSA-N methyl 5-hydroxy-8-[[2-(trifluoromethyl)phenyl]methyl]-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC=C1C(F)(F)F NFKZUNBTGGOYET-UHFFFAOYSA-N 0.000 description 1
• YAAFHPCNTNTEEB-UHFFFAOYSA-N methyl 5-hydroxy-8-[[3-(trifluoromethoxy)phenyl]methyl]-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC(OC(F)(F)F)=C1 YAAFHPCNTNTEEB-UHFFFAOYSA-N 0.000 description 1
• GEHIQDZATHASGF-UHFFFAOYSA-N methyl 5-hydroxy-8-[[3-(trifluoromethyl)phenyl]methyl]-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC(C(F)(F)F)=C1 GEHIQDZATHASGF-UHFFFAOYSA-N 0.000 description 1
• VYTNZQJWZUYBQE-UHFFFAOYSA-N methyl 5-oxo-8-(pyridin-3-ylmethyl)-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CN=C1 VYTNZQJWZUYBQE-UHFFFAOYSA-N 0.000 description 1
• MUJYXSFRZGCNOZ-UHFFFAOYSA-N methyl 5-oxo-8-[(3-phenoxyphenyl)methyl]-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC(C=1)=CC=CC=1OC1=CC=CC=C1 MUJYXSFRZGCNOZ-UHFFFAOYSA-N 0.000 description 1
• IPJFPRBENXFRAM-UHFFFAOYSA-N methyl 5-oxo-8-[[2-(trifluoromethyl)phenyl]methyl]-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC=C1C(F)(F)F IPJFPRBENXFRAM-UHFFFAOYSA-N 0.000 description 1
• FJZREPYGVSKYKK-UHFFFAOYSA-N methyl 5-oxo-8-[[3-(trifluoromethoxy)phenyl]methyl]-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC(OC(F)(F)F)=C1 FJZREPYGVSKYKK-UHFFFAOYSA-N 0.000 description 1
• LVQOUDKUNKIAAY-UHFFFAOYSA-N methyl 5-oxo-8-[[3-(trifluoromethyl)phenyl]methyl]-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC(C(F)(F)F)=C1 LVQOUDKUNKIAAY-UHFFFAOYSA-N 0.000 description 1
• LLEOFYFCHLBTBJ-UHFFFAOYSA-N methyl 5-oxo-9-[[2-(trifluoromethyl)phenyl]methyl]-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1C(F)(F)F LLEOFYFCHLBTBJ-UHFFFAOYSA-N 0.000 description 1
• YDADMHVBELPYRF-UHFFFAOYSA-N methyl 5-oxo-9-[[3-(trifluoromethoxy)phenyl]methyl]-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC(OC(F)(F)F)=C1 YDADMHVBELPYRF-UHFFFAOYSA-N 0.000 description 1
• ZPNGYRPSWVQROU-UHFFFAOYSA-N methyl 7-(furan-2-yl)-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1C(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2CC1C1=CC=CO1 ZPNGYRPSWVQROU-UHFFFAOYSA-N 0.000 description 1
• BHPDQZPWRCGIIW-UHFFFAOYSA-N methyl 7-methyl-8-[(3-methylphenyl)methyl]-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound CC1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC(C)=C1 BHPDQZPWRCGIIW-UHFFFAOYSA-N 0.000 description 1
• SUYVZIOYJWVSJW-UHFFFAOYSA-N methyl 8-(cyclopentylmethyl)-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1CCCC1 SUYVZIOYJWVSJW-UHFFFAOYSA-N 0.000 description 1
• ZEJPSGCVVKNPPK-UHFFFAOYSA-N methyl 8-[(2,3-difluorophenyl)methyl]-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC(F)=C1F ZEJPSGCVVKNPPK-UHFFFAOYSA-N 0.000 description 1
• OIVCMCCYGDDZIW-UHFFFAOYSA-N methyl 8-[(2,6-dichlorophenyl)methyl]-5-hydroxy-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=C(Cl)C=CC=C1Cl OIVCMCCYGDDZIW-UHFFFAOYSA-N 0.000 description 1
• WGSFTXRHOGAUIQ-UHFFFAOYSA-N methyl 8-[(2,6-difluorophenyl)methyl]-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=C(F)C=CC=C1F WGSFTXRHOGAUIQ-UHFFFAOYSA-N 0.000 description 1
• VTRPEPBNRKALSA-UHFFFAOYSA-N methyl 8-[(2-benzylphenyl)methyl]-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC=C1CC1=CC=CC=C1 VTRPEPBNRKALSA-UHFFFAOYSA-N 0.000 description 1
• IPMOWRZNUJLVIJ-UHFFFAOYSA-N methyl 8-[(2-fluorophenyl)methyl]-5-hydroxy-9h-carbazole-4-carboxylate Chemical compound C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC=C1F IPMOWRZNUJLVIJ-UHFFFAOYSA-N 0.000 description 1
• PSUWMGDNEDHTRX-UHFFFAOYSA-N methyl 8-[(2-fluorophenyl)methyl]-5-oxo-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC=C1F PSUWMGDNEDHTRX-UHFFFAOYSA-N 0.000 description 1
• LLJBLIUDIZNGAE-UHFFFAOYSA-N methyl 8-[(3-fluorophenyl)methyl]-5-hydroxy-7-methyl-9h-carbazole-4-carboxylate Chemical compound CC1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC(F)=C1 LLJBLIUDIZNGAE-UHFFFAOYSA-N 0.000 description 1
• UOJWZSYHSNVSCI-UHFFFAOYSA-N methyl 8-benzyl-5-hydroxy-7-[4-(trifluoromethyl)phenyl]-9h-carbazole-4-carboxylate Chemical compound C=1C=C(C(F)(F)F)C=CC=1C1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC=C1 UOJWZSYHSNVSCI-UHFFFAOYSA-N 0.000 description 1
• FMMQJOKFRIRBOQ-UHFFFAOYSA-N methyl 8-benzyl-5-hydroxy-7-methyl-9h-carbazole-4-carboxylate Chemical compound CC1=CC(O)=C2C=3C(C(=O)OC)=CC=CC=3NC2=C1CC1=CC=CC=C1 FMMQJOKFRIRBOQ-UHFFFAOYSA-N 0.000 description 1
• BHDFQVHWKNUUBP-UHFFFAOYSA-N methyl 8-benzyl-5-oxo-7-[4-(trifluoromethyl)phenyl]-6,7,8,9-tetrahydrocarbazole-4-carboxylate Chemical compound C=1C=C(C(F)(F)F)C=CC=1C1CC(=O)C=2C=3C(C(=O)OC)=CC=CC=3NC=2C1CC1=CC=CC=C1 BHDFQVHWKNUUBP-UHFFFAOYSA-N 0.000 description 1
• GKDFGTVUWFSFSG-UHFFFAOYSA-N methyl 9-[(2,6-dichlorophenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=C(Cl)C=CC=C1Cl GKDFGTVUWFSFSG-UHFFFAOYSA-N 0.000 description 1
• NQJOZJJMFTYKAS-UHFFFAOYSA-N methyl 9-[(2,6-difluorophenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=C(F)C=CC=C1F NQJOZJJMFTYKAS-UHFFFAOYSA-N 0.000 description 1
• WBHWSVHRGPRIAZ-UHFFFAOYSA-N methyl 9-[(2-methylphenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1C WBHWSVHRGPRIAZ-UHFFFAOYSA-N 0.000 description 1
• HCGFOPKRNGMOKA-UHFFFAOYSA-N methyl 9-[(3,5-dimethylphenyl)methyl]-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CCCC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC(C)=CC(C)=C1 HCGFOPKRNGMOKA-UHFFFAOYSA-N 0.000 description 1
• UWKQMTAHLXBKDM-UHFFFAOYSA-N methyl 9-benzyl-5-hydroxy-7-[4-(trifluoromethyl)phenyl]carbazole-4-carboxylate Chemical compound C12=CC(C=3C=CC(=CC=3)C(F)(F)F)=CC(O)=C2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 UWKQMTAHLXBKDM-UHFFFAOYSA-N 0.000 description 1
• TUFAGSKTLXPHPK-UHFFFAOYSA-N methyl 9-benzyl-5-oxo-7-[4-(trifluoromethyl)phenyl]-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CC(C=3C=CC(=CC=3)C(F)(F)F)CC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 TUFAGSKTLXPHPK-UHFFFAOYSA-N 0.000 description 1
• CATQTVAHJGQIGC-UHFFFAOYSA-N methyl 9-benzyl-7-(hydroxymethyl)-5-oxo-7,8-dihydro-6h-carbazole-4-carboxylate Chemical compound C1=2CC(CO)CC(=O)C=2C=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 CATQTVAHJGQIGC-UHFFFAOYSA-N 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
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• 239000002808 molecular sieve Substances 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• NPKYYJGDHWBTSU-UHFFFAOYSA-N n-benzyl-3,5-dimethoxyaniline Chemical compound COC1=CC(OC)=CC(NCC=2C=CC=CC=2)=C1 NPKYYJGDHWBTSU-UHFFFAOYSA-N 0.000 description 1
• NSBIQPJIWUJBBX-UHFFFAOYSA-N n-methoxyaniline Chemical compound CONC1=CC=CC=C1 NSBIQPJIWUJBBX-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 230000000802 nitrating effect Effects 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
• 239000012454 non-polar solvent Substances 0.000 description 1
• 239000004533 oil dispersion Substances 0.000 description 1
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• 150000002894 organic compounds Chemical class 0.000 description 1
• 238000012261 overproduction Methods 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• 150000003003 phosphines Chemical class 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 208000030428 polyarticular arthritis Diseases 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 238000012746 preparative thin layer chromatography Methods 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 239000002516 radical scavenger Substances 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
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• 229910052703 rhodium Inorganic materials 0.000 description 1
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• 239000012266 salt solution Substances 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
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• DGBCEDABANLFFU-UHFFFAOYSA-N tert-butyl 2-[5-carbamoyl-9-[(2-chlorophenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC(C)(C)C)=CC=CC=2N1CC1=CC=CC=C1Cl DGBCEDABANLFFU-UHFFFAOYSA-N 0.000 description 1
• AMQKSDOYCMKXIW-UHFFFAOYSA-N tert-butyl 2-[5-carbamoyl-9-[(3-chlorophenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC(C)(C)C)=CC=CC=2N1CC1=CC=CC(Cl)=C1 AMQKSDOYCMKXIW-UHFFFAOYSA-N 0.000 description 1
• RXOVTHCDTPBQBX-UHFFFAOYSA-N tert-butyl 2-[5-carbamoyl-9-[(3-fluorophenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC(C)(C)C)=CC=CC=2N1CC1=CC=CC(F)=C1 RXOVTHCDTPBQBX-UHFFFAOYSA-N 0.000 description 1
• PQLOIVOTHAHYNC-UHFFFAOYSA-N tert-butyl 2-[5-carbamoyl-9-[(3-phenoxyphenyl)methyl]carbazol-4-yl]oxyacetate Chemical compound C12=CC=CC(C(N)=O)=C2C=2C(OCC(=O)OC(C)(C)C)=CC=CC=2N1CC(C=1)=CC=CC=1OC1=CC=CC=C1 PQLOIVOTHAHYNC-UHFFFAOYSA-N 0.000 description 1
• ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
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• LHJCZOXMCGQVDQ-UHFFFAOYSA-N tri(propan-2-yl)silyl trifluoromethanesulfonate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OS(=O)(=O)C(F)(F)F LHJCZOXMCGQVDQ-UHFFFAOYSA-N 0.000 description 1
• DHWBYAACHDUFAT-UHFFFAOYSA-N tricyclopentylphosphane Chemical compound C1CCCC1P(C1CCCC1)C1CCCC1 DHWBYAACHDUFAT-UHFFFAOYSA-N 0.000 description 1
• VOITXYVAKOUIBA-UHFFFAOYSA-N triethylaluminium Chemical compound CC[Al](CC)CC VOITXYVAKOUIBA-UHFFFAOYSA-N 0.000 description 1
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• GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
• IGNTWNVBGLNYDV-UHFFFAOYSA-N triisopropylphosphine Chemical compound CC(C)P(C(C)C)C(C)C IGNTWNVBGLNYDV-UHFFFAOYSA-N 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
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