ZA200701257B - Vasopressin V10 antagonists - Google Patents
Vasopressin V10 antagonists Download PDFInfo
- Publication number
- ZA200701257B ZA200701257B ZA200701257A ZA200701257A ZA200701257B ZA 200701257 B ZA200701257 B ZA 200701257B ZA 200701257 A ZA200701257 A ZA 200701257A ZA 200701257 A ZA200701257 A ZA 200701257A ZA 200701257 B ZA200701257 B ZA 200701257B
- Authority
- ZA
- South Africa
- Prior art keywords
- methyl
- dihydro
- benzo
- alkyl
- tetraaza
- Prior art date
Links
- 239000005557 antagonist Substances 0.000 title abstract description 17
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 title abstract description 13
- 108010004977 Vasopressins Proteins 0.000 title abstract description 13
- 102000002852 Vasopressins Human genes 0.000 title abstract description 13
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 title abstract description 13
- 229960003726 vasopressin Drugs 0.000 title abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 257
- 206010013935 Dysmenorrhoea Diseases 0.000 claims abstract description 30
- 238000011282 treatment Methods 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 208000003782 Raynaud disease Diseases 0.000 claims abstract description 8
- 208000012322 Raynaud phenomenon Diseases 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims description 182
- 125000000217 alkyl group Chemical group 0.000 claims description 144
- -1 3, 3-Dimethyl-butyl Chemical group 0.000 claims description 107
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 239000000460 chlorine Substances 0.000 claims description 55
- 229910052801 chlorine Inorganic materials 0.000 claims description 50
- 229910052731 fluorine Inorganic materials 0.000 claims description 49
- 125000001072 heteroaryl group Chemical group 0.000 claims description 41
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 125000005605 benzo group Chemical group 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 32
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 32
- 239000011737 fluorine Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 229910052794 bromium Inorganic materials 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- XKIHBTCFABIZQB-UHFFFAOYSA-N 1-(3,3-dimethylbutyl)piperidine-4-carboxylic acid Chemical compound CC(C)(C)CCN1CCC(C(O)=O)CC1 XKIHBTCFABIZQB-UHFFFAOYSA-N 0.000 claims description 15
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- QKDHYIZFSYQRHO-UHFFFAOYSA-N 1-(cyclopropylmethyl)piperidin-1-ium-4-carboxylate Chemical compound C1CC(C(=O)O)CCN1CC1CC1 QKDHYIZFSYQRHO-UHFFFAOYSA-N 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- GFNNSSDMSQAIRF-UHFFFAOYSA-N 4-(3,3-dimethylbutyl)piperazine-1-carboxylic acid Chemical compound CC(C)(C)CCN1CCN(C(O)=O)CC1 GFNNSSDMSQAIRF-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 229910052721 tungsten Inorganic materials 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- 206010048962 Brain oedema Diseases 0.000 claims description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 6
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 206010021036 Hyponatraemia Diseases 0.000 claims description 6
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 6
- 230000036506 anxiety Effects 0.000 claims description 6
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 6
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 201000005577 familial hyperlipidemia Diseases 0.000 claims description 6
- 201000003152 motion sickness Diseases 0.000 claims description 6
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 125000005024 alkenyl aryl group Chemical group 0.000 claims description 5
- 208000037805 labour Diseases 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 3
- NCDGLWDTYSURSA-UHFFFAOYSA-N benzo[f]azulene Chemical compound C1=C2C=CC=CC2=CC2=CC=CC2=C1 NCDGLWDTYSURSA-UHFFFAOYSA-N 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 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 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 2
- MBFPLEORHAUCCA-UHFFFAOYSA-N 4-(cyclopropylmethyl)piperazine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCN1CC1CC1 MBFPLEORHAUCCA-UHFFFAOYSA-N 0.000 claims 9
- XLJPAYUPSAOBOW-UHFFFAOYSA-N 4-(cyclopentylmethyl)piperazine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCN1CC1CCCC1 XLJPAYUPSAOBOW-UHFFFAOYSA-N 0.000 claims 4
- XWAKKTVNLCOLLW-UHFFFAOYSA-N 4-propylpiperazine-1-carboxylic acid Chemical compound CCCN1CCN(C(O)=O)CC1 XWAKKTVNLCOLLW-UHFFFAOYSA-N 0.000 claims 3
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 claims 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 3
- MZNDFFYWFRAVOU-UHFFFAOYSA-N 4-(2-methylpropyl)piperazine-1-carboxylic acid Chemical compound CC(C)CN1CCN(C(O)=O)CC1 MZNDFFYWFRAVOU-UHFFFAOYSA-N 0.000 claims 2
- APXAQGKXDVCHRC-UHFFFAOYSA-N 4-(3-methylbutyl)piperazine-1-carboxylic acid Chemical compound CC(C)CCN1CCN(C(O)=O)CC1 APXAQGKXDVCHRC-UHFFFAOYSA-N 0.000 claims 2
- WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims 2
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims 2
- 229940047889 isobutyramide Drugs 0.000 claims 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 2
- 150000003053 piperidines Chemical class 0.000 claims 2
- 229940080818 propionamide Drugs 0.000 claims 2
- 125000003107 substituted aryl group Chemical group 0.000 claims 2
- MWANNMGHGHQDAO-UHFFFAOYSA-N 1-(3,3-dimethylbutyl)-N-[[2-fluoro-4-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]piperidine-4-carboxamide Chemical compound FC1=C(CNC(=O)C2CCN(CC2)CCC(C)(C)C)C=CC(=C1)C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=CC=C2 MWANNMGHGHQDAO-UHFFFAOYSA-N 0.000 claims 1
- OAKZWDIRTRECMB-UHFFFAOYSA-N 1-(3,3-dimethylbutyl)-N-[[2-methyl-4-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]piperidine-4-carboxamide Chemical compound CC1=C(CNC(=O)C2CCN(CC2)CCC(C)(C)C)C=CC(=C1)C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=CC=C2 OAKZWDIRTRECMB-UHFFFAOYSA-N 0.000 claims 1
- UOORDZYPZJJIQS-UHFFFAOYSA-N 1-(3,3-dimethylbutyl)-N-[[3-methyl-4-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]piperidine-4-carboxamide Chemical compound CC=1C=C(CNC(=O)C2CCN(CC2)CCC(C)(C)C)C=CC1C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=CC=C2 UOORDZYPZJJIQS-UHFFFAOYSA-N 0.000 claims 1
- MCIDXCJVQGRQMH-UHFFFAOYSA-N 1-(3,3-dimethylbutyl)-N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]piperidine-4-carboxamide Chemical compound CN1N=CC=2CN(C3=C(NC12)C=C(C=C3)C)C(=O)C3=CC(=C(CNC(=O)C1CCN(CC1)CCC(C)(C)C)C=C3)F MCIDXCJVQGRQMH-UHFFFAOYSA-N 0.000 claims 1
- KVDROKQIGCRFHW-UHFFFAOYSA-N 1-(3,3-dimethylbutyl)-N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-3-methylphenyl]methyl]piperidine-4-carboxamide Chemical compound CN1N=CC=2CN(C3=C(NC12)C=C(C=C3)C)C(=O)C3=C(C=C(CNC(=O)C1CCN(CC1)CCC(C)(C)C)C=C3)C KVDROKQIGCRFHW-UHFFFAOYSA-N 0.000 claims 1
- LLIAXIZQAQHAHT-UHFFFAOYSA-N 1-(3,3-dimethylbutyl)-n-[[2-methyl-4-(2-methyl-4,5-dihydro-3h-imidazo[4,5-d][1]benzazepine-6-carbonyl)phenyl]methyl]piperidine-4-carboxamide Chemical compound C12=CC=CC=C2C=2NC(C)=NC=2CCN1C(=O)C(C=C1C)=CC=C1CNC(=O)C1CCN(CCC(C)(C)C)CC1 LLIAXIZQAQHAHT-UHFFFAOYSA-N 0.000 claims 1
- VLWXDARVFYYWMA-UHFFFAOYSA-N 1-(3,3-dimethylbutyl)-n-[[2-methyl-4-(2-methyl-4,5-dihydro-[1,3]oxazolo[4,5-d][1]benzazepine-6-carbonyl)phenyl]methyl]piperidine-4-carboxamide Chemical compound C12=CC=CC=C2C=2OC(C)=NC=2CCN1C(=O)C(C=C1C)=CC=C1CNC(=O)C1CCN(CCC(C)(C)C)CC1 VLWXDARVFYYWMA-UHFFFAOYSA-N 0.000 claims 1
- PCJQCEYGJKTNMX-UHFFFAOYSA-N 1-(cyclopropylmethyl)-N-[[2-methyl-4-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]piperidine-4-carboxamide Chemical compound CC1=C(CNC(=O)C2CCN(CC2)CC2CC2)C=CC(=C1)C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=CC=C2 PCJQCEYGJKTNMX-UHFFFAOYSA-N 0.000 claims 1
- TVDIKKQQXQTWOE-UHFFFAOYSA-N 1-(cyclopropylmethyl)-N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-methylphenyl]methyl]piperidine-4-carboxamide Chemical compound CN1N=CC=2CN(C3=C(NC12)C=C(C=C3)C)C(=O)C3=CC(=C(CNC(=O)C1CCN(CC1)CC1CC1)C=C3)C TVDIKKQQXQTWOE-UHFFFAOYSA-N 0.000 claims 1
- BRXWUTOQSFINOI-UHFFFAOYSA-N 1-[4-(3,3-dimethylbutyl)piperazin-1-yl]-4-[2-methyl-4-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]butan-1-one Chemical compound Cc1cc(ccc1CCCC(=O)N1CCN(CCC(C)(C)C)CC1)C(=O)N1Cc2cnn(C)c2Nc2ccccc12 BRXWUTOQSFINOI-UHFFFAOYSA-N 0.000 claims 1
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- UKBYHIKMBVDQRT-UHFFFAOYSA-N 4-(2,2-dimethylpropyl)piperazine-1-carboxylic acid Chemical compound CC(C)(C)CN1CCN(C(O)=O)CC1 UKBYHIKMBVDQRT-UHFFFAOYSA-N 0.000 claims 1
- SJLOIPNOJKJIAL-UHFFFAOYSA-N 4-(3,3-dimethylbutyl)-N-[[4-(1,9-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]piperazine-1-carboxamide Chemical compound Cc1cccc2N(Cc3cnn(C)c3Nc12)C(=O)c1ccc(CNC(=O)N2CCN(CCC(C)(C)C)CC2)c(F)c1 SJLOIPNOJKJIAL-UHFFFAOYSA-N 0.000 claims 1
- QLNMXNSGLRREDB-UHFFFAOYSA-N 4-(3,3-dimethylbutyl)-n-[[2-methyl-4-(2-methyl-4,5-dihydro-3h-imidazo[4,5-d][1]benzazepine-6-carbonyl)phenyl]methyl]piperazine-1-carboxamide Chemical compound C12=CC=CC=C2C=2NC(C)=NC=2CCN1C(=O)C(C=C1C)=CC=C1CNC(=O)N1CCN(CCC(C)(C)C)CC1 QLNMXNSGLRREDB-UHFFFAOYSA-N 0.000 claims 1
- FDSRJVGKHKCUSB-UHFFFAOYSA-N 4-(3,3-dimethylbutyl)-n-[[2-methyl-4-(2-methyl-4,5-dihydro-[1,3]oxazolo[4,5-d][1]benzazepine-6-carbonyl)phenyl]methyl]piperazine-1-carboxamide Chemical compound C12=CC=CC=C2C=2OC(C)=NC=2CCN1C(=O)C(C=C1C)=CC=C1CNC(=O)N1CCN(CCC(C)(C)C)CC1 FDSRJVGKHKCUSB-UHFFFAOYSA-N 0.000 claims 1
- LOGBHGNCQCFQAG-UHFFFAOYSA-N 4-(3,3-dimethylbutyl)-n-[[2-methyl-4-(8-methyl-3,4-dihydro-2h-quinoline-1-carbonyl)phenyl]methyl]piperazine-1-carboxamide Chemical compound CC1=CC(C(=O)N2C3=C(C)C=CC=C3CCC2)=CC=C1CNC(=O)N1CCN(CCC(C)(C)C)CC1 LOGBHGNCQCFQAG-UHFFFAOYSA-N 0.000 claims 1
- PRPZAHVFMXNIQH-UHFFFAOYSA-N 4-(cyclopropylmethyl)-N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-3-fluorophenyl]methyl]piperazine-1-carboxamide Chemical compound Cc1ccc2N(Cc3cnn(C)c3Nc2c1)C(=O)c1ccc(CNC(=O)N2CCN(CC3CC3)CC2)cc1F PRPZAHVFMXNIQH-UHFFFAOYSA-N 0.000 claims 1
- HKCWGKYQRDVKBQ-UHFFFAOYSA-N 4-(cyclopropylmethyl)-N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-3-methylphenyl]methyl]piperazine-1-carboxamide Chemical compound Cc1ccc2N(Cc3cnn(C)c3Nc2c1)C(=O)c1ccc(CNC(=O)N2CCN(CC3CC3)CC2)cc1C HKCWGKYQRDVKBQ-UHFFFAOYSA-N 0.000 claims 1
- HPLCMEFBCAZXFH-UHFFFAOYSA-N N-[[2-chloro-4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]cyclopropanecarboxamide Chemical compound ClC1=C(CNC(=O)C2CC2)C=CC(=C1)C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=C(C=C2)C HPLCMEFBCAZXFH-UHFFFAOYSA-N 0.000 claims 1
- KWHYGGAPPWZBGG-UHFFFAOYSA-N N-[[2-chloro-4-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]-1-(cyclopropylmethyl)piperidine-4-carboxamide Chemical compound ClC1=C(CNC(=O)C2CCN(CC2)CC2CC2)C=CC(=C1)C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=CC=C2 KWHYGGAPPWZBGG-UHFFFAOYSA-N 0.000 claims 1
- QYCFYRDBJAXOJI-UHFFFAOYSA-N N-[[2-chloro-4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]-1-(3,3-dimethylbutyl)piperidine-4-carboxamide Chemical compound Cn1ncc2CN(C(=O)c3ccc(CNC(=O)C4CCN(CCC(C)(C)C)CC4)c(Cl)c3)c3ccc(Cl)cc3Nc12 QYCFYRDBJAXOJI-UHFFFAOYSA-N 0.000 claims 1
- UULBUWMEKIXYHV-UHFFFAOYSA-N N-[[2-chloro-4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]-1-(cyclopropylmethyl)piperidine-4-carboxamide Chemical compound ClC1=C(CNC(=O)C2CCN(CC2)CC2CC2)C=CC(=C1)C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=C(C=C2)Cl UULBUWMEKIXYHV-UHFFFAOYSA-N 0.000 claims 1
- ZBVRXCDTUABCIM-UHFFFAOYSA-N N-[[2-chloro-4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NCc1ccc(cc1Cl)C(=O)N1Cc2cnn(C)c2Nc2cc(Cl)ccc12 ZBVRXCDTUABCIM-UHFFFAOYSA-N 0.000 claims 1
- NSQJIILIFACDJS-UHFFFAOYSA-N N-[[2-chloro-4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]butanamide Chemical compound CCCC(=O)NCc1ccc(cc1Cl)C(=O)N1Cc2cnn(C)c2Nc2cc(Cl)ccc12 NSQJIILIFACDJS-UHFFFAOYSA-N 0.000 claims 1
- QWDJVMNWRLNTPQ-UHFFFAOYSA-N N-[[2-chloro-4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]propanamide Chemical compound CCC(=O)NCc1ccc(cc1Cl)C(=O)N1Cc2cnn(C)c2Nc2cc(Cl)ccc12 QWDJVMNWRLNTPQ-UHFFFAOYSA-N 0.000 claims 1
- DIHBJUXWUHPKSM-UHFFFAOYSA-N N-[[2-fluoro-4-(8-fluoro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]cyclopropanecarboxamide Chemical compound FC1=C(CNC(=O)C2CC2)C=CC(=C1)C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=C(C=C2)F DIHBJUXWUHPKSM-UHFFFAOYSA-N 0.000 claims 1
- WSAXMDUQXUDGHT-UHFFFAOYSA-N N-[[2-fluoro-4-(8-fluoro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]propanamide Chemical compound CCC(=O)NCc1ccc(cc1F)C(=O)N1Cc2cnn(C)c2Nc2cc(F)ccc12 WSAXMDUQXUDGHT-UHFFFAOYSA-N 0.000 claims 1
- HCVJAXPBAZKISZ-UHFFFAOYSA-N N-[[3-chloro-4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]-1-(3,3-dimethylbutyl)piperidine-4-carboxamide Chemical compound ClC=1C=C(CNC(=O)C2CCN(CC2)CCC(C)(C)C)C=CC1C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=C(C=C2)C HCVJAXPBAZKISZ-UHFFFAOYSA-N 0.000 claims 1
- PGQNNYNAFSNNKW-UHFFFAOYSA-N N-[[3-chloro-4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]-1-(cyclopropylmethyl)piperidine-4-carboxamide Chemical compound ClC=1C=C(CNC(=O)C2CCN(CC2)CC2CC2)C=CC1C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=C(C=C2)C PGQNNYNAFSNNKW-UHFFFAOYSA-N 0.000 claims 1
- RJNYXCNUBSBEIX-UHFFFAOYSA-N N-[[3-chloro-4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]cyclopropanecarboxamide Chemical compound ClC=1C=C(CNC(=O)C2CC2)C=CC1C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=C(C=C2)Cl RJNYXCNUBSBEIX-UHFFFAOYSA-N 0.000 claims 1
- MWPCPRPYFFPSTN-UHFFFAOYSA-N N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]cyclopentanecarboxamide Chemical compound CN1N=CC=2CN(C3=C(NC12)C=C(C=C3)C)C(=O)C3=CC(=C(CNC(=O)C1CCCC1)C=C3)F MWPCPRPYFFPSTN-UHFFFAOYSA-N 0.000 claims 1
- TZQIVQBWCHLLRW-UHFFFAOYSA-N N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-methylphenyl]methyl]-4-(2-methylpropyl)piperazine-1-carboxamide Chemical compound CN1N=CC=2CN(C3=C(NC12)C=C(C=C3)C)C(=O)C3=CC(=C(CNC(=O)N1CCN(CC1)CC(C)C)C=C3)C TZQIVQBWCHLLRW-UHFFFAOYSA-N 0.000 claims 1
- NIVCRLSHZUEYOR-UHFFFAOYSA-N N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-methylphenyl]methyl]-4-(3-methylbutyl)piperazine-1-carboxamide Chemical compound CN1N=CC=2CN(C3=C(NC12)C=C(C=C3)C)C(=O)C3=CC(=C(CNC(=O)N1CCN(CC1)CCC(C)C)C=C3)C NIVCRLSHZUEYOR-UHFFFAOYSA-N 0.000 claims 1
- YDYOQIOGJFDZNJ-UHFFFAOYSA-N N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-methylphenyl]methyl]cyclopropanecarboxamide Chemical compound CN1N=CC=2CN(C3=C(NC12)C=C(C=C3)C)C(=O)C3=CC(=C(CNC(=O)C1CC1)C=C3)C YDYOQIOGJFDZNJ-UHFFFAOYSA-N 0.000 claims 1
- WQNSNSUCLUCLRN-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]-1-(3,3-dimethylbutyl)piperidine-4-carboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=CC(=C(CNC(=O)C3CCN(CC3)CCC(C)(C)C)C=C2)F)C)C1 WQNSNSUCLUCLRN-UHFFFAOYSA-N 0.000 claims 1
- LOYOTBBLCNDWCM-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NCc1ccc(cc1F)C(=O)N1Cc2cnn(C)c2Nc2cc(Cl)ccc12 LOYOTBBLCNDWCM-UHFFFAOYSA-N 0.000 claims 1
- NICOXDJJBUETPN-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]cyclobutanecarboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=CC(=C(CNC(=O)C3CCC3)C=C2)F)C)C1 NICOXDJJBUETPN-UHFFFAOYSA-N 0.000 claims 1
- HSJZCNNIWCKJPI-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]cyclopentanecarboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=CC(=C(CNC(=O)C3CCCC3)C=C2)F)C)C1 HSJZCNNIWCKJPI-UHFFFAOYSA-N 0.000 claims 1
- KSPRPQSFFDXQAL-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]formamide Chemical compound Cn1ncc2CN(C(=O)c3ccc(CNC=O)c(F)c3)c3ccc(Cl)cc3Nc12 KSPRPQSFFDXQAL-UHFFFAOYSA-N 0.000 claims 1
- FHYQIFRQTIQDKH-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]propanamide Chemical compound CCC(=O)NCc1ccc(cc1F)C(=O)N1Cc2cnn(C)c2Nc2cc(Cl)ccc12 FHYQIFRQTIQDKH-UHFFFAOYSA-N 0.000 claims 1
- JYTNIEYXSXQWRT-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-methylphenyl]methyl]-1-(cyclopropylmethyl)piperidine-4-carboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=CC(=C(CNC(=O)C3CCN(CC3)CC3CC3)C=C2)C)C)C1 JYTNIEYXSXQWRT-UHFFFAOYSA-N 0.000 claims 1
- FNHHOWYLNPAQHV-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-methylphenyl]methyl]-4-(2-methylpropyl)piperazine-1-carboxamide Chemical compound CC(C)CN1CCN(CC1)C(=O)NCc1ccc(cc1C)C(=O)N1Cc2cnn(C)c2Nc2cc(Cl)ccc12 FNHHOWYLNPAQHV-UHFFFAOYSA-N 0.000 claims 1
- KCBDQFYNBWYNHJ-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-methylphenyl]methyl]-4-(3,3-dimethylbutyl)piperazine-1-carboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=CC(=C(CNC(=O)N3CCN(CC3)CCC(C)(C)C)C=C2)C)C)C1 KCBDQFYNBWYNHJ-UHFFFAOYSA-N 0.000 claims 1
- UGFRSODUKPKUJO-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-methylphenyl]methyl]-4-(cyclopropylmethyl)piperazine-1-carboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=CC(=C(CNC(=O)N3CCN(CC3)CC3CC3)C=C2)C)C)C1 UGFRSODUKPKUJO-UHFFFAOYSA-N 0.000 claims 1
- DQCLBRPBWNLLLY-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-methylphenyl]methyl]-4-propylpiperazine-1-carboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=CC(=C(CNC(=O)N3CCN(CC3)CCC)C=C2)C)C)C1 DQCLBRPBWNLLLY-UHFFFAOYSA-N 0.000 claims 1
- DZLYFDUKRUYUIP-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-methylphenyl]methyl]cyclopropanecarboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=CC(=C(CNC(=O)C3CC3)C=C2)C)C)C1 DZLYFDUKRUYUIP-UHFFFAOYSA-N 0.000 claims 1
- YVROXNTYHPJGEO-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-3-fluorophenyl]methyl]-1-(cyclopropylmethyl)piperidine-4-carboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=C(C=C(CNC(=O)C3CCN(CC3)CC3CC3)C=C2)F)C)C1 YVROXNTYHPJGEO-UHFFFAOYSA-N 0.000 claims 1
- GBFGRRQWVDHUSE-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-3-fluorophenyl]methyl]cyclopropanecarboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=C(C=C(CNC(=O)C3CC3)C=C2)F)C)C1 GBFGRRQWVDHUSE-UHFFFAOYSA-N 0.000 claims 1
- NMANJEJISGTRHX-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-3-methylphenyl]methyl]-1-(3,3-dimethylbutyl)piperidine-4-carboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=C(C=C(CNC(=O)C3CCN(CC3)CCC(C)(C)C)C=C2)C)C)C1 NMANJEJISGTRHX-UHFFFAOYSA-N 0.000 claims 1
- ZDNWQTBLTCUEFL-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-3-methylphenyl]methyl]-4-(3,3-dimethylbutyl)piperazine-1-carboxamide Chemical compound Cc1cc(CNC(=O)N2CCN(CCC(C)(C)C)CC2)ccc1C(=O)N1Cc2cnn(C)c2Nc2cc(Cl)ccc12 ZDNWQTBLTCUEFL-UHFFFAOYSA-N 0.000 claims 1
- COWAWYZRZCWKHP-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-3-methylphenyl]methyl]cyclopropanecarboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2=C(C=C(CNC(=O)C3CC3)C=C2)C)C)C1 COWAWYZRZCWKHP-UHFFFAOYSA-N 0.000 claims 1
- BQKGWZBZBQHJIX-UHFFFAOYSA-N N-[[4-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)cyclohexyl]methyl]cyclopropanecarboxamide Chemical compound ClC=1C=CC2=C(NC=3N(N=CC3CN2C(=O)C2CCC(CC2)CNC(=O)C2CC2)C)C1 BQKGWZBZBQHJIX-UHFFFAOYSA-N 0.000 claims 1
- 101001026581 Rhizobium radiobacter Kanamycin resistance protein Proteins 0.000 claims 1
- JHYCTEGETBQBNI-UHFFFAOYSA-N [4-(aminomethyl)-2-chlorophenyl]-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)methanone Chemical compound Cc1ccc2N(Cc3cnn(C)c3Nc2c1)C(=O)c1ccc(CN)cc1Cl JHYCTEGETBQBNI-UHFFFAOYSA-N 0.000 claims 1
- SRUSCDZAUWCATL-UHFFFAOYSA-N [4-(aminomethyl)-2-fluorophenyl]-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)methanone Chemical compound Cn1ncc2CN(C(=O)c3ccc(CN)cc3F)c3ccc(Cl)cc3Nc12 SRUSCDZAUWCATL-UHFFFAOYSA-N 0.000 claims 1
- DJTHREKTMXNHPV-UHFFFAOYSA-N [4-(aminomethyl)-2-methylphenyl]-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)methanone Chemical compound Cc1ccc2N(Cc3cnn(C)c3Nc2c1)C(=O)c1ccc(CN)cc1C DJTHREKTMXNHPV-UHFFFAOYSA-N 0.000 claims 1
- HSTVHPADQHVYMP-UHFFFAOYSA-N [4-(aminomethyl)-3-chlorophenyl]-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)methanone Chemical compound Cc1ccc2N(Cc3cnn(C)c3Nc2c1)C(=O)c1ccc(CN)c(Cl)c1 HSTVHPADQHVYMP-UHFFFAOYSA-N 0.000 claims 1
- NCSFZTBMROQPLZ-UHFFFAOYSA-N [4-(aminomethyl)-3-chlorophenyl]-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)methanone Chemical compound Cn1ncc2CN(C(=O)c3ccc(CN)c(Cl)c3)c3ccccc3Nc12 NCSFZTBMROQPLZ-UHFFFAOYSA-N 0.000 claims 1
- ZACATHYNBDNNAI-UHFFFAOYSA-N [4-(aminomethyl)-3-chlorophenyl]-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)methanone Chemical compound NCC1=C(C=C(C=C1)C(=O)N1C2=C(NC=3N(N=CC3C1)C)C=C(C=C2)Cl)Cl ZACATHYNBDNNAI-UHFFFAOYSA-N 0.000 claims 1
- DFOVXMCHOHJHCW-UHFFFAOYSA-N [4-(aminomethyl)-3-fluorophenyl]-(8-chloro-1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)methanone Chemical compound NCC1=C(C=C(C=C1)C(=O)N1C2=C(NC=3N(N=CC=3C1)C)C=C(C=C2)Cl)F DFOVXMCHOHJHCW-UHFFFAOYSA-N 0.000 claims 1
- 125000002877 alkyl aryl group Chemical group 0.000 claims 1
- 150000001538 azepines Chemical class 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
- 125000004175 fluorobenzyl group Chemical group 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- CEODOVTZJYYUQC-UHFFFAOYSA-N n-[[4-(8-chloro-3,4-dihydro-2h-1,5-benzoxazepine-5-carbonyl)-2-methylphenyl]methyl]-4-(3,3-dimethylbutyl)piperazine-1-carboxamide Chemical compound CC1=CC(C(=O)N2C3=CC=C(Cl)C=C3OCCC2)=CC=C1CNC(=O)N1CCN(CCC(C)(C)C)CC1 CEODOVTZJYYUQC-UHFFFAOYSA-N 0.000 claims 1
- BXQXPERCFVNVME-UHFFFAOYSA-N n-[[4-(9-chloro-2-methyl-4,5-dihydro-3h-imidazo[4,5-d][1]benzazepine-6-carbonyl)-2-methylphenyl]methyl]-2-methylpropanamide Chemical compound C1=C(C)C(CNC(=O)C(C)C)=CC=C1C(=O)N1C2=CC=C(Cl)C=C2C(NC(C)=N2)=C2CC1 BXQXPERCFVNVME-UHFFFAOYSA-N 0.000 claims 1
- KPWPWFVFUKFEBH-UHFFFAOYSA-N n-[[4-[(4-chlorophenyl)-methylcarbamoyl]-2-methylphenyl]methyl]-1-(3,3-dimethylbutyl)piperidine-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C(C=C1C)=CC=C1CNC(=O)C1CCN(CCC(C)(C)C)CC1 KPWPWFVFUKFEBH-UHFFFAOYSA-N 0.000 claims 1
- UKQVJQVASVVYPF-UHFFFAOYSA-N n-[[4-[(4-chlorophenyl)-methylcarbamoyl]-2-methylphenyl]methyl]-1-(cyclopropylmethyl)piperidine-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C(C=C1C)=CC=C1CNC(=O)C(CC1)CCN1CC1CC1 UKQVJQVASVVYPF-UHFFFAOYSA-N 0.000 claims 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 259
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 195
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 190
- 239000000243 solution Substances 0.000 description 149
- 235000019439 ethyl acetate Nutrition 0.000 description 92
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 84
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 81
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 67
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
- 239000000741 silica gel Substances 0.000 description 62
- 229910002027 silica gel Inorganic materials 0.000 description 62
- 238000003818 flash chromatography Methods 0.000 description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- 239000012267 brine Substances 0.000 description 53
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 53
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- 238000010992 reflux Methods 0.000 description 43
- 239000002904 solvent Substances 0.000 description 43
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 229920006395 saturated elastomer Polymers 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 125000004429 atom Chemical group 0.000 description 26
- 239000000706 filtrate Substances 0.000 description 26
- 239000007787 solid Substances 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 25
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
- 239000000725 suspension Substances 0.000 description 19
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 15
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- 229960005419 nitrogen Drugs 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- 229940093956 potassium carbonate Drugs 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 229910021529 ammonia Inorganic materials 0.000 description 9
- 229960000510 ammonia Drugs 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 229940057952 methanol Drugs 0.000 description 7
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 7
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- 101800000989 Oxytocin Proteins 0.000 description 6
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 6
- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- GPSDUZXPYCFOSQ-UHFFFAOYSA-N m-toluic acid Chemical compound CC1=CC=CC(C(O)=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 6
- 229960001723 oxytocin Drugs 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 239000001117 sulphuric acid Substances 0.000 description 6
- 235000011149 sulphuric acid Nutrition 0.000 description 6
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 5
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- GSEVGUWNJHVGDB-UHFFFAOYSA-N 1-(3,3-dimethylbutyl)piperazine;dihydrochloride Chemical compound Cl.Cl.CC(C)(C)CCN1CCNCC1 GSEVGUWNJHVGDB-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- WTDFFADXONGQOM-UHFFFAOYSA-N formaldehyde;hydrochloride Chemical compound Cl.O=C WTDFFADXONGQOM-UHFFFAOYSA-N 0.000 description 4
- 150000002431 hydrogen Chemical group 0.000 description 4
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 235000007686 potassium Nutrition 0.000 description 4
- 229960003975 potassium Drugs 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 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 4
- 229920002554 vinyl polymer Polymers 0.000 description 4
- MIRKJFHKYOINEZ-UHFFFAOYSA-N 3-fluoro-4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoic acid Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(C(O)=O)C=C1F MIRKJFHKYOINEZ-UHFFFAOYSA-N 0.000 description 3
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- ZJQMLJFHCKTCSF-UHFFFAOYSA-N benzyl 4-formylpiperidine-1-carboxylate Chemical compound C1CC(C=O)CCN1C(=O)OCC1=CC=CC=C1 ZJQMLJFHCKTCSF-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229940074995 bromine Drugs 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 230000004907 flux Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluenecarboxylic acid Natural products CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- CWXOAQXKPAENDI-UHFFFAOYSA-N sodium methylsulfinylmethylide Chemical compound [Na+].CS([CH2-])=O CWXOAQXKPAENDI-UHFFFAOYSA-N 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- MHSGOABISYIYKP-UHFFFAOYSA-N (4-nitrophenyl)methyl carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(COC(Cl)=O)C=C1 MHSGOABISYIYKP-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- MFVDBTNSEJNWBG-UHFFFAOYSA-N 1-(3,3-dimethylbutyl)piperazine;hydrochloride Chemical compound Cl.CC(C)(C)CCN1CCNCC1 MFVDBTNSEJNWBG-UHFFFAOYSA-N 0.000 description 2
- MHQDVDDGNWZBQF-UHFFFAOYSA-N 1-(cyclopropylmethyl)imidazolidine Chemical compound C1CNCN1CC1CC1 MHQDVDDGNWZBQF-UHFFFAOYSA-N 0.000 description 2
- PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 2
- YAHHFPJGDOWLGU-UHFFFAOYSA-N 1-methyl-5,10-dihydro-4H-pyrazolo[4,3-c][1,5]benzodiazepine Chemical compound Cn1ncc2CNc3ccccc3Nc12 YAHHFPJGDOWLGU-UHFFFAOYSA-N 0.000 description 2
- VCRYFPSMXFXRIO-UHFFFAOYSA-N 2-(4-methoxycarbonyl-2-methylphenyl)acetic acid Chemical compound COC(=O)C1=CC=C(CC(O)=O)C(C)=C1 VCRYFPSMXFXRIO-UHFFFAOYSA-N 0.000 description 2
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 2
- WIPYZRZPNMUSER-UHFFFAOYSA-N 2-chloro-4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1Cl WIPYZRZPNMUSER-UHFFFAOYSA-N 0.000 description 2
- LAAJSNVULAUCQT-UHFFFAOYSA-N 2-n-cyclohexyl-1-n-methylbenzene-1,2-diamine Chemical compound CNC1=CC=CC=C1NC1CCCCC1 LAAJSNVULAUCQT-UHFFFAOYSA-N 0.000 description 2
- YQACKMXMLJSWFM-UHFFFAOYSA-N 2-n-cyclohexylbenzene-1,2-diamine Chemical compound NC1=CC=CC=C1NC1CCCCC1 YQACKMXMLJSWFM-UHFFFAOYSA-N 0.000 description 2
- ZVSJTXJNNKGWRU-UHFFFAOYSA-N 3-(4-methoxycarbonyl-2-methylphenyl)propanoic acid Chemical compound COC(=O)C1=CC=C(CCC(O)=O)C(C)=C1 ZVSJTXJNNKGWRU-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- IUSDEKNMCOUBEE-UHFFFAOYSA-N 3-fluoro-4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(F)=C1 IUSDEKNMCOUBEE-UHFFFAOYSA-N 0.000 description 2
- JPKLUMRKPCFBPG-UHFFFAOYSA-N 3-methyl-4-[4-[(2-methylpropan-2-yl)oxy]-4-oxobutoxy]benzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1OCCCC(=O)OC(C)(C)C JPKLUMRKPCFBPG-UHFFFAOYSA-N 0.000 description 2
- QAFXAJNSSCJOFC-UHFFFAOYSA-N 4-(4-methoxycarbonyl-2-methylphenyl)butanoic acid Chemical compound COC(=O)C1=CC=C(CCCC(O)=O)C(C)=C1 QAFXAJNSSCJOFC-UHFFFAOYSA-N 0.000 description 2
- FJHZIJMOPWGZMP-UHFFFAOYSA-N 4-(5-methoxy-5-oxopentyl)-3-methylbenzoic acid Chemical compound COC(=O)CCCCC1=CC=C(C(O)=O)C=C1C FJHZIJMOPWGZMP-UHFFFAOYSA-N 0.000 description 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
- BDNFXFFGDLNGLT-UHFFFAOYSA-N 4-[3-[4-(3,3-dimethylbutyl)piperazin-1-yl]-3-oxopropyl]-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1CCC(=O)N1CCN(CCC(C)(C)C)CC1 BDNFXFFGDLNGLT-UHFFFAOYSA-N 0.000 description 2
- LTRYUAZFLOGRLJ-UHFFFAOYSA-N 4-cyano-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1C#N LTRYUAZFLOGRLJ-UHFFFAOYSA-N 0.000 description 2
- LTFHNKUKQYVHDX-UHFFFAOYSA-N 4-hydroxy-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1O LTFHNKUKQYVHDX-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 230000000332 continued effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 2
- QEOZGTBBNDHZSK-UHFFFAOYSA-N ethyl 3-fluoro-4-hydroxybenzoate Chemical compound CCOC(=O)C1=CC=C(O)C(F)=C1 QEOZGTBBNDHZSK-UHFFFAOYSA-N 0.000 description 2
- VKQBEDORPYEQOF-UHFFFAOYSA-N ethyl 5-(2-amino-4-chloroanilino)-1-methylpyrazole-4-carboxylate Chemical compound C1=NN(C)C(NC=2C(=CC(Cl)=CC=2)N)=C1C(=O)OCC VKQBEDORPYEQOF-UHFFFAOYSA-N 0.000 description 2
- MEUSJJFWVKBUFP-UHFFFAOYSA-N ethyl 5-amino-1-methylpyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C)C=1N MEUSJJFWVKBUFP-UHFFFAOYSA-N 0.000 description 2
- RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000005906 menstruation Effects 0.000 description 2
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 2
- PNBYWOIWUKQGPR-UHFFFAOYSA-N methyl 2-[(4-methylphenyl)sulfonylamino]benzoate Chemical compound COC(=O)C1=CC=CC=C1NS(=O)(=O)C1=CC=C(C)C=C1 PNBYWOIWUKQGPR-UHFFFAOYSA-N 0.000 description 2
- BJZFMXJQJZUATE-UHFFFAOYSA-N methyl 2-chloro-4-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(O)C=C1Cl BJZFMXJQJZUATE-UHFFFAOYSA-N 0.000 description 2
- FFABMXUZZRNTIC-UHFFFAOYSA-N methyl 3-fluoro-4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoate Chemical compound COC(=O)C1=CC=C(CNC(=O)OC(C)(C)C)C(F)=C1 FFABMXUZZRNTIC-UHFFFAOYSA-N 0.000 description 2
- RAFFOVQBMRBRCS-UHFFFAOYSA-N methyl 3-fluoro-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(F)=C1 RAFFOVQBMRBRCS-UHFFFAOYSA-N 0.000 description 2
- KZRXBASAYFZHTA-UHFFFAOYSA-N methyl 3-methyl-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]benzoate Chemical compound COC(=O)C1=CC=C(CC(=O)OC(C)(C)C)C(C)=C1 KZRXBASAYFZHTA-UHFFFAOYSA-N 0.000 description 2
- JIOBWBRCFYROPH-UHFFFAOYSA-N methyl 4-(aminomethyl)-3-fluorobenzoate Chemical compound COC(=O)C1=CC=C(CN)C(F)=C1 JIOBWBRCFYROPH-UHFFFAOYSA-N 0.000 description 2
- CYGJEWIECWOXNH-UHFFFAOYSA-N methyl 4-(aminomethyl)-3-methylbenzoate Chemical compound COC(=O)C1=CC=C(CN)C(C)=C1 CYGJEWIECWOXNH-UHFFFAOYSA-N 0.000 description 2
- XEMCSCSKWYFGEC-UHFFFAOYSA-N methyl 4-(azidomethyl)-3-fluorobenzoate Chemical compound COC(=O)C1=CC=C(CN=[N+]=[N-])C(F)=C1 XEMCSCSKWYFGEC-UHFFFAOYSA-N 0.000 description 2
- OJBQAHZJVDWSFD-UHFFFAOYSA-N methyl 4-(bromomethyl)-3-fluorobenzoate Chemical compound COC(=O)C1=CC=C(CBr)C(F)=C1 OJBQAHZJVDWSFD-UHFFFAOYSA-N 0.000 description 2
- GTZTYNPAPQKIIR-UHFFFAOYSA-N methyl 4-bromo-3-methylbenzoate Chemical compound COC(=O)C1=CC=C(Br)C(C)=C1 GTZTYNPAPQKIIR-UHFFFAOYSA-N 0.000 description 2
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000002632 myometrial effect Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 2
- LFJTTZCBJLCUIV-UHFFFAOYSA-N tert-butyl 4-(2-bromoacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CBr)CC1 LFJTTZCBJLCUIV-UHFFFAOYSA-N 0.000 description 2
- LZDXNCDPNLESJR-UHFFFAOYSA-N tert-butyl 4-(3,3-dimethylbutyl)piperazine-1-carboxylate Chemical compound CC(C)(C)CCN1CCN(C(=O)OC(C)(C)C)CC1 LZDXNCDPNLESJR-UHFFFAOYSA-N 0.000 description 2
- JRUWOZGXPPMIKT-UHFFFAOYSA-N tert-butyl 4-[3-(4-ethoxycarbonyl-2-fluorophenoxy)propyl]piperazine-1-carboxylate Chemical compound FC1=CC(C(=O)OCC)=CC=C1OCCCN1CCN(C(=O)OC(C)(C)C)CC1 JRUWOZGXPPMIKT-UHFFFAOYSA-N 0.000 description 2
- HJEZRYIJNHAIGY-UHFFFAOYSA-N tert-butyl 4-bromobutanoate Chemical compound CC(C)(C)OC(=O)CCCBr HJEZRYIJNHAIGY-UHFFFAOYSA-N 0.000 description 2
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
- LSHRIHCMOOHMLN-UHFFFAOYSA-N (1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)-[3-methyl-4-[3-[1-(2-methylpropyl)piperidin-4-yl]propoxy]phenyl]methanone Chemical compound CC(C)CN1CCC(CCCOc2ccc(cc2C)C(=O)N2Cc3cnn(C)c3Nc3cc(C)ccc23)CC1 LSHRIHCMOOHMLN-UHFFFAOYSA-N 0.000 description 1
- LRWMDDRBYJCMHU-UHFFFAOYSA-N (1-benzyl-2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6-yl)-phenylmethanone Chemical compound C12=CC=CC=C2C=2N(CC=3C=CC=CC=3)C(C)=NC=2CCN1C(=O)C1=CC=CC=C1 LRWMDDRBYJCMHU-UHFFFAOYSA-N 0.000 description 1
- QXDIILRTNRPWIJ-UHFFFAOYSA-N (2-methyl-4,5-dihydro-3h-imidazo[4,5-d][1]benzazepin-6-yl)-phenylmethanone Chemical compound C12=CC=CC=C2C=2NC(C)=NC=2CCN1C(=O)C1=CC=CC=C1 QXDIILRTNRPWIJ-UHFFFAOYSA-N 0.000 description 1
- KDNZVCHHBVNTIC-UHFFFAOYSA-N (2-methyl-4,5-dihydro-[1,3]oxazolo[4,5-d][1]benzazepin-6-yl)-phenylmethanone Chemical compound C12=CC=CC=C2C=2OC(C)=NC=2CCN1C(=O)C1=CC=CC=C1 KDNZVCHHBVNTIC-UHFFFAOYSA-N 0.000 description 1
- ZHQHZASVCXJQKE-UHFFFAOYSA-N (2-methyl-4,5-dihydro-[1,3]thiazolo[5,4-d][1]benzazepin-6-yl)-phenylmethanone Chemical compound S1C(C)=NC(C2=CC=CC=C22)=C1CCN2C(=O)C1=CC=CC=C1 ZHQHZASVCXJQKE-UHFFFAOYSA-N 0.000 description 1
- BJFIDCADFRDPIO-DZCXQCEKSA-N (2S)-N-[(2S)-6-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxohexan-2-yl]-1-[[(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-13-(phenylmethyl)-1,2-dithia-5,8,11,14,17-pentazacycloeicos-4-yl]-oxomethyl]-2-pyrrolidinecarboxamide Chemical compound NCCCC[C@@H](C(=O)NCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](N)CSSC1 BJFIDCADFRDPIO-DZCXQCEKSA-N 0.000 description 1
- RCBOBTFDFDRLEI-MDZDMXLPSA-N (E)-3-[2-methyl-4-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]prop-2-enoic acid Chemical compound c1cc(\C=C\C(O)=O)c(C)cc1C(=O)N(c1ccccc1N1)Cc2c1n(C)nc2 RCBOBTFDFDRLEI-MDZDMXLPSA-N 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- CIDNZJVUTPAGHW-UHFFFAOYSA-N 1,3-dibromopropane;ethyl 4-(3-bromopropoxy)-3-fluorobenzoate Chemical compound BrCCCBr.CCOC(=O)C1=CC=C(OCCCBr)C(F)=C1 CIDNZJVUTPAGHW-UHFFFAOYSA-N 0.000 description 1
- YMUSMYLWAKSOCO-UHFFFAOYSA-N 1-(2-methylpropyl)piperidin-1-ium-4-carboxylate Chemical compound CC(C)CN1CCC(C(O)=O)CC1 YMUSMYLWAKSOCO-UHFFFAOYSA-N 0.000 description 1
- JIWAFPAMZFQRRK-UHFFFAOYSA-N 1-benzoyl-3,4-dihydro-2h-1-benzazepin-5-one Chemical compound C1CCC(=O)C2=CC=CC=C2N1C(=O)C1=CC=CC=C1 JIWAFPAMZFQRRK-UHFFFAOYSA-N 0.000 description 1
- GSAVCUBEEMMTLP-UHFFFAOYSA-N 1-benzoyl-4-bromo-3,4-dihydro-2h-1-benzazepin-5-one Chemical compound C12=CC=CC=C2C(=O)C(Br)CCN1C(=O)C1=CC=CC=C1 GSAVCUBEEMMTLP-UHFFFAOYSA-N 0.000 description 1
- DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- YEQAMPOYHLICPF-UHFFFAOYSA-N 1-piperazin-1-ylpropan-1-one Chemical compound CCC(=O)N1CCNCC1 YEQAMPOYHLICPF-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- DVSLBDBGAXXLKZ-UHFFFAOYSA-N 2,3-diethylbenzamide Chemical compound CCC1=CC=CC(C(N)=O)=C1CC DVSLBDBGAXXLKZ-UHFFFAOYSA-N 0.000 description 1
- 125000006069 2,3-dimethyl-2-butenyl group Chemical group 0.000 description 1
- FZCQMIRJCGWWCL-UHFFFAOYSA-N 2-amino-5-chlorophenol Chemical compound NC1=CC=C(Cl)C=C1O FZCQMIRJCGWWCL-UHFFFAOYSA-N 0.000 description 1
- PBCMDYUKTAPSQS-UHFFFAOYSA-N 2-bromo-1-[4-(3,3-dimethylbutyl)piperazin-1-yl]ethanone Chemical compound CC(C)(C)CCN1CCN(C(=O)CBr)CC1 PBCMDYUKTAPSQS-UHFFFAOYSA-N 0.000 description 1
- RIYFONBSYWACFF-UHFFFAOYSA-N 2-bromoethylcyclopropane Chemical compound BrCCC1CC1 RIYFONBSYWACFF-UHFFFAOYSA-N 0.000 description 1
- UZRXSKHRPHIYOK-UHFFFAOYSA-N 2-chloro-4-[2-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-2-oxoethoxy]benzoic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(=O)COC1=CC=C(C(O)=O)C(Cl)=C1 UZRXSKHRPHIYOK-UHFFFAOYSA-N 0.000 description 1
- BDDVAWDNVWLHDQ-UHFFFAOYSA-N 2-chloro-4-hydroxybenzonitrile Chemical compound OC1=CC=C(C#N)C(Cl)=C1 BDDVAWDNVWLHDQ-UHFFFAOYSA-N 0.000 description 1
- WZMOWQCNPFDWPA-UHFFFAOYSA-N 2-fluoro-4-methyl-1-nitrobenzene Chemical compound CC1=CC=C([N+]([O-])=O)C(F)=C1 WZMOWQCNPFDWPA-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- ZUZVEFIYLJDAKK-UHFFFAOYSA-N 2-methyl-5,6-dihydro-4h-[1,3]oxazolo[4,5-d][1]benzazepine Chemical compound C1CNC2=CC=CC=C2C2=C1N=C(C)O2 ZUZVEFIYLJDAKK-UHFFFAOYSA-N 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- ISOBNJYSFHFSJB-UHFFFAOYSA-N 2-piperidin-4-ylacetamide;hydrochloride Chemical compound Cl.NC(=O)CC1CCNCC1 ISOBNJYSFHFSJB-UHFFFAOYSA-N 0.000 description 1
- LTVRSJBNXLZFGT-UHFFFAOYSA-N 2-silylethenone Chemical compound [SiH3]C=C=O LTVRSJBNXLZFGT-UHFFFAOYSA-N 0.000 description 1
- LTNUSYNQZJZUSY-UHFFFAOYSA-N 3,3-dimethylbutanal Chemical compound CC(C)(C)CC=O LTNUSYNQZJZUSY-UHFFFAOYSA-N 0.000 description 1
- VIQBSKNXZMXPLY-UHFFFAOYSA-N 3,3-dimethylbutanal ethyl 1-(3,3-dimethylbutyl)piperidine-4-carboxylate Chemical compound CC(CC=O)(C)C.C(C)OC(=O)C1CCN(CC1)CCC(C)(C)C VIQBSKNXZMXPLY-UHFFFAOYSA-N 0.000 description 1
- RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 description 1
- MSFOWXTUZJNLOT-UHFFFAOYSA-N 3-[2-methyl-4-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]propanoic acid Chemical compound Cc1cc(ccc1CCC(O)=O)C(=O)N1Cc2cnn(C)c2Nc2ccccc12 MSFOWXTUZJNLOT-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- ZIQRTIWAACNZBM-UHFFFAOYSA-N 3-fluoro-4-[3-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]propoxy]benzoic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CCCOC1=CC=C(C(O)=O)C=C1F ZIQRTIWAACNZBM-UHFFFAOYSA-N 0.000 description 1
- XUQCONCMPCVUDM-UHFFFAOYSA-N 3-fluoro-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1F XUQCONCMPCVUDM-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- WEKYIJHXOMEIHK-BQYQJAHWSA-N 3-methyl-4-[(e)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]benzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1\C=C\C(=O)OC(C)(C)C WEKYIJHXOMEIHK-BQYQJAHWSA-N 0.000 description 1
- MFSXNPUVPYWTBN-UHFFFAOYSA-N 3-methyl-4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1CNC(=O)OC(C)(C)C MFSXNPUVPYWTBN-UHFFFAOYSA-N 0.000 description 1
- OEHCYRZYVZKUGM-UHFFFAOYSA-N 3-pyridin-3-yl-4,5-dihydro-1,2-oxazole-5-carboxylic acid Chemical compound O1C(C(=O)O)CC(C=2C=NC=CC=2)=N1 OEHCYRZYVZKUGM-UHFFFAOYSA-N 0.000 description 1
- PVYCHTWXOPDNCE-UHFFFAOYSA-N 4-(1,3-dioxolan-2-yl)piperidine Chemical compound O1CCOC1C1CCNCC1 PVYCHTWXOPDNCE-UHFFFAOYSA-N 0.000 description 1
- CXGBQFCVKGMFDO-UHFFFAOYSA-N 4-(1,3-dioxolan-2-yl)piperidine-1-carboxylic acid Chemical compound O1C(OCC1)C1CCN(CC1)C(=O)O CXGBQFCVKGMFDO-UHFFFAOYSA-N 0.000 description 1
- QCMVDWNLTSWUQM-UHFFFAOYSA-N 4-(3,3-dimethylbutyl)-N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]piperazine-1-carboxamide Chemical compound Cc1ccc2N(Cc3cnn(C)c3Nc2c1)C(=O)c1ccc(CNC(=O)N2CCN(CCC(C)(C)C)CC2)c(F)c1 QCMVDWNLTSWUQM-UHFFFAOYSA-N 0.000 description 1
- WSIRMUHMGPWRSH-UHFFFAOYSA-N 4-(4-methoxycarbonyl-2-methylphenyl)butanoic acid;3-(4-methoxycarbonyl-2-methylphenyl)propanoic acid Chemical compound COC(=O)C1=CC=C(CCC(O)=O)C(C)=C1.COC(=O)C1=CC=C(CCCC(O)=O)C(C)=C1 WSIRMUHMGPWRSH-UHFFFAOYSA-N 0.000 description 1
- AMJARISXWDOLOY-UHFFFAOYSA-N 4-(carboxymethoxy)-3-methylbenzoic acid Chemical compound C(=O)(O)COC1=C(C=C(C(=O)O)C=C1)C AMJARISXWDOLOY-UHFFFAOYSA-N 0.000 description 1
- NRPWRWBCSGUQGV-UHFFFAOYSA-N 4-[3-(4-cyclopropylpiperazin-1-yl)propoxy]-3-fluorobenzoic acid Chemical compound FC1=CC(C(=O)O)=CC=C1OCCCN1CCN(C2CC2)CC1 NRPWRWBCSGUQGV-UHFFFAOYSA-N 0.000 description 1
- YDJHKOZBQROARD-UHFFFAOYSA-N 4-[3-(4-cyclopropylpiperazin-1-yl)propoxy]-3-fluorobenzoic acid;ethyl 4-[3-(4-cyclopropylpiperazin-1-yl)propoxy]-3-fluorobenzoate Chemical compound FC1=CC(C(=O)O)=CC=C1OCCCN1CCN(C2CC2)CC1.FC1=CC(C(=O)OCC)=CC=C1OCCCN1CCN(C2CC2)CC1 YDJHKOZBQROARD-UHFFFAOYSA-N 0.000 description 1
- AZEKNJGFCSHZID-UHFFFAOYSA-N 4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]cyclohexane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NCC1CCC(C(O)=O)CC1 AZEKNJGFCSHZID-UHFFFAOYSA-N 0.000 description 1
- XPYQFIISZQCINN-QVXDJYSKSA-N 4-amino-1-[(2r,3e,4s,5r)-3-(fluoromethylidene)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one;hydrate Chemical compound O.O=C1N=C(N)C=CN1[C@H]1C(=C/F)/[C@H](O)[C@@H](CO)O1 XPYQFIISZQCINN-QVXDJYSKSA-N 0.000 description 1
- MBDUKNCPOPMRJQ-UHFFFAOYSA-N 4-amino-2-chlorobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C(Cl)=C1 MBDUKNCPOPMRJQ-UHFFFAOYSA-N 0.000 description 1
- HNYFIXLYLGMBBF-UHFFFAOYSA-N 4-bromo-3-methylbenzoic acid;tert-butyl 4-bromo-3-methylbenzoate Chemical compound CC1=CC(C(O)=O)=CC=C1Br.CC1=CC(C(=O)OC(C)(C)C)=CC=C1Br HNYFIXLYLGMBBF-UHFFFAOYSA-N 0.000 description 1
- PTCPUGKKWNMITF-UHFFFAOYSA-N 4-chloro-2-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1F PTCPUGKKWNMITF-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- HEOQXHNKRXRCTO-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-benzo[7]annulene Chemical compound C1CCCCC2=CC=CC=C21 HEOQXHNKRXRCTO-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- KETPEHIYJWLDGZ-UHFFFAOYSA-N 8-chloro-1-methyl-5,10-dihydro-4H-pyrazolo[4,3-c][1,5]benzodiazepine Chemical compound Cn1ncc2CNc3ccc(Cl)cc3Nc12 KETPEHIYJWLDGZ-UHFFFAOYSA-N 0.000 description 1
- MMQRNIDZYSDNPQ-UHFFFAOYSA-N 8-chloro-2,3,4,5-tetrahydro-1,5-benzoxazepine Chemical compound N1CCCOC2=CC(Cl)=CC=C21 MMQRNIDZYSDNPQ-UHFFFAOYSA-N 0.000 description 1
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 1
- 229910014585 C2-Ce Inorganic materials 0.000 description 1
- SZDDCFPLRCQBSC-UHFFFAOYSA-N CC(CC=O)(C)C.COC(C1=CC(=C(C=C1)OCCN1CCN(CC1)CCC(C)(C)C)C)=O Chemical compound CC(CC=O)(C)C.COC(C1=CC(=C(C=C1)OCCN1CCN(CC1)CCC(C)(C)C)C)=O SZDDCFPLRCQBSC-UHFFFAOYSA-N 0.000 description 1
- HHUVGBODFDVOFB-UHFFFAOYSA-N COC(C1=CC(=C(C=C1)N)C)=O.COC(C1=CC(=C(C=C1)O)C)=O Chemical compound COC(C1=CC(=C(C=C1)N)C)=O.COC(C1=CC(=C(C=C1)O)C)=O HHUVGBODFDVOFB-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021594 Copper(II) fluoride Inorganic materials 0.000 description 1
- OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 101100536354 Drosophila melanogaster tant gene Proteins 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 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 1
- 108010048179 Lypressin Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004236 Ponceau SX Substances 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- LYJQBDPUQQSGDE-UHFFFAOYSA-N [4-[3-[4-(3,3-dimethylbutyl)piperazin-1-yl]propoxy]-3-fluorophenyl]-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)methanone Chemical compound Cn1ncc2CN(C(=O)c3ccc(OCCCN4CCN(CCC(C)(C)C)CC4)c(F)c3)c3ccccc3Nc12 LYJQBDPUQQSGDE-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000002686 anti-diuretic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- LINIORCIRVAZSM-UHFFFAOYSA-N benzyl 4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound C1CC(CO)CCN1C(=O)OCC1=CC=CC=C1 LINIORCIRVAZSM-UHFFFAOYSA-N 0.000 description 1
- KFOIFRFPHCAQAT-UHFFFAOYSA-N benzyl 4-[(cyclopropylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC2CC2)CCN1C(=O)OCC1=CC=CC=C1 KFOIFRFPHCAQAT-UHFFFAOYSA-N 0.000 description 1
- YXJTZFHYBNZNEU-UHFFFAOYSA-N benzyl 4-[[cyclopropyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]methyl]piperidine-1-carboxylate tert-butyl N-cyclopropyl-N-(piperidin-4-ylmethyl)carbamate Chemical compound C(C1=CC=CC=C1)OC(=O)N1CCC(CC1)CN(C1CC1)C(=O)OC(C)(C)C.C(C)(C)(C)OC(N(CC1CCNCC1)C1CC1)=O YXJTZFHYBNZNEU-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229930188620 butyrolactone Natural products 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 229950005499 carbon tetrachloride Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- GFHNAMRJFCEERV-UHFFFAOYSA-L cobalt chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Co+2] GFHNAMRJFCEERV-UHFFFAOYSA-L 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229940108928 copper Drugs 0.000 description 1
- GWFAVIIMQDUCRA-UHFFFAOYSA-L copper(ii) fluoride Chemical compound [F-].[F-].[Cu+2] GWFAVIIMQDUCRA-UHFFFAOYSA-L 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- QUCIYPGYOCSJOM-UHFFFAOYSA-N ethyl 1-(3,3-dimethylbutyl)piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCN(CCC(C)(C)C)CC1 QUCIYPGYOCSJOM-UHFFFAOYSA-N 0.000 description 1
- ZSGJABYQNHABCH-UHFFFAOYSA-N ethyl 1-methyl-5-(2-nitroanilino)pyrazole-4-carboxylate Chemical compound C1=NN(C)C(NC=2C(=CC=CC=2)[N+]([O-])=O)=C1C(=O)OCC ZSGJABYQNHABCH-UHFFFAOYSA-N 0.000 description 1
- NHEULSVQISCXHG-UHFFFAOYSA-N ethyl 1-methyl-5-(4-methyl-2-nitroanilino)pyrazole-4-carboxylate Chemical compound C1=NN(C)C(NC=2C(=CC(C)=CC=2)[N+]([O-])=O)=C1C(=O)OCC NHEULSVQISCXHG-UHFFFAOYSA-N 0.000 description 1
- PBOYGYXGAGTCMY-UHFFFAOYSA-N ethyl 1h-azepine-4-carboxylate Chemical compound CCOC(=O)C1=CC=CNC=C1 PBOYGYXGAGTCMY-UHFFFAOYSA-N 0.000 description 1
- KACZQOKEFKFNDB-UHFFFAOYSA-N ethyl 1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1 KACZQOKEFKFNDB-UHFFFAOYSA-N 0.000 description 1
- SXPALFRWFJQPFQ-UHFFFAOYSA-N ethyl 2-chloro-4-hydroxybenzoate Chemical compound CCOC(=O)C1=CC=C(O)C=C1Cl SXPALFRWFJQPFQ-UHFFFAOYSA-N 0.000 description 1
- ZDRYEZKVPUWVPG-UHFFFAOYSA-N ethyl 5-(2-amino-4-methylanilino)-1-methylpyrazole-4-carboxylate Chemical compound C1=NN(C)C(NC=2C(=CC(C)=CC=2)N)=C1C(=O)OCC ZDRYEZKVPUWVPG-UHFFFAOYSA-N 0.000 description 1
- VLRMKYHACWWZEJ-UHFFFAOYSA-N ethyl 5-(2-aminoanilino)-1-methylpyrazole-4-carboxylate Chemical compound C1=NN(C)C(NC=2C(=CC=CC=2)N)=C1C(=O)OCC VLRMKYHACWWZEJ-UHFFFAOYSA-N 0.000 description 1
- IINKOOGWNBCFOE-UHFFFAOYSA-N ethyl 5-(2-aminoanilino)-1-methylpyrazole-4-carboxylate;ethyl 1-methyl-5-(2-nitroanilino)pyrazole-4-carboxylate Chemical compound C1=NN(C)C(NC=2C(=CC=CC=2)N)=C1C(=O)OCC.C1=NN(C)C(NC=2C(=CC=CC=2)[N+]([O-])=O)=C1C(=O)OCC IINKOOGWNBCFOE-UHFFFAOYSA-N 0.000 description 1
- VKRVVJVQAHSSLQ-UHFFFAOYSA-N ethyl 5-(4-chloro-2-nitroanilino)-1-methylpyrazole-4-carboxylate Chemical compound C1=NN(C)C(NC=2C(=CC(Cl)=CC=2)[N+]([O-])=O)=C1C(=O)OCC VKRVVJVQAHSSLQ-UHFFFAOYSA-N 0.000 description 1
- LMCNNNDDRPWZJT-UHFFFAOYSA-N ethyl 5-hydroxy-1-(4-methylphenyl)sulfonyl-2,3-dihydro-1-benzazepine-4-carboxylate Chemical compound C1CC(C(=O)OCC)=C(O)C2=CC=CC=C2N1S(=O)(=O)C1=CC=C(C)C=C1 LMCNNNDDRPWZJT-UHFFFAOYSA-N 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 229960003837 lypressin Drugs 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- JAVRNIFMYIJXIE-UHFFFAOYSA-N methyl 2-chlorobenzoate Chemical compound COC(=O)C1=CC=CC=C1Cl JAVRNIFMYIJXIE-UHFFFAOYSA-N 0.000 description 1
- SUHLUMKZPUMAFP-UHFFFAOYSA-N methyl 2-hydroxy-3-methylbenzoate Chemical compound COC(=O)C1=CC=CC(C)=C1O SUHLUMKZPUMAFP-UHFFFAOYSA-N 0.000 description 1
- WVWZECQNFWFVFW-UHFFFAOYSA-N methyl 2-methylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C WVWZECQNFWFVFW-UHFFFAOYSA-N 0.000 description 1
- FOCWREHRYLFXFJ-UHFFFAOYSA-N methyl 3-methyl-4-(2-piperazin-1-ylethoxy)benzoate;dihydrochloride Chemical compound Cl.Cl.CC1=CC(C(=O)OC)=CC=C1OCCN1CCNCC1 FOCWREHRYLFXFJ-UHFFFAOYSA-N 0.000 description 1
- YQTPWYLLGOUVPN-CMDGGOBGSA-N methyl 3-methyl-4-[(e)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]benzoate Chemical compound COC(=O)C1=CC=C(\C=C\C(=O)OC(C)(C)C)C(C)=C1 YQTPWYLLGOUVPN-CMDGGOBGSA-N 0.000 description 1
- JOUDNOLAZMIYBK-UHFFFAOYSA-N methyl 3-methyl-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]benzoate Chemical compound COC(=O)C1=CC=C(OCC(=O)OC(C)(C)C)C(C)=C1 JOUDNOLAZMIYBK-UHFFFAOYSA-N 0.000 description 1
- OLFRLOGTIUVYHY-UHFFFAOYSA-N methyl 3-methyl-4-[4-[(2-methylpropan-2-yl)oxy]-4-oxobutoxy]benzoate Chemical compound COC(=O)C1=CC=C(OCCCC(=O)OC(C)(C)C)C(C)=C1 OLFRLOGTIUVYHY-UHFFFAOYSA-N 0.000 description 1
- WAGSGHIIJKPOHK-UHFFFAOYSA-N methyl 3-methyl-4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoate Chemical compound COC(=O)C1=CC=C(CNC(=O)OC(C)(C)C)C(C)=C1 WAGSGHIIJKPOHK-UHFFFAOYSA-N 0.000 description 1
- LIXWSMOADOOTOR-UHFFFAOYSA-N methyl 4-cyano-3-methylbenzoate Chemical compound COC(=O)C1=CC=C(C#N)C(C)=C1 LIXWSMOADOOTOR-UHFFFAOYSA-N 0.000 description 1
- QBMHMOKIFSCFCX-UHFFFAOYSA-N methyl 4-hydroxy-3-methylbenzoate Chemical compound COC(=O)C1=CC=C(O)C(C)=C1 QBMHMOKIFSCFCX-UHFFFAOYSA-N 0.000 description 1
- ISSBXVABPNVYMM-UHFFFAOYSA-N methyl 5-hydroxy-1-(4-methylphenyl)sulfonyl-2,3-dihydro-1-benzazepine-4-carboxylate Chemical compound C1CC(C(=O)OC)=C(O)C2=CC=CC=C2N1S(=O)(=O)C1=CC=C(C)C=C1 ISSBXVABPNVYMM-UHFFFAOYSA-N 0.000 description 1
- 229940102398 methyl anthranilate Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- OCYUKRNENNMFCG-UHFFFAOYSA-N n-(4-chloro-2-hydroxyphenyl)benzamide Chemical compound OC1=CC(Cl)=CC=C1NC(=O)C1=CC=CC=C1 OCYUKRNENNMFCG-UHFFFAOYSA-N 0.000 description 1
- NENZSHGMDIEWOH-UHFFFAOYSA-N n-cyclohexyl-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=CC=C1NC1CCCCC1 NENZSHGMDIEWOH-UHFFFAOYSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 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
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 210000001883 posterior pituitary gland Anatomy 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- IALUUOKJPBOFJL-UHFFFAOYSA-N potassium oxidosilane Chemical compound [K+].[SiH3][O-] IALUUOKJPBOFJL-UHFFFAOYSA-N 0.000 description 1
- LBKJNHPKYFYCLL-UHFFFAOYSA-N potassium;trimethyl(oxido)silane Chemical compound [K+].C[Si](C)(C)[O-] LBKJNHPKYFYCLL-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- CLDWGXZGFUNWKB-UHFFFAOYSA-M silver;benzoate Chemical compound [Ag+].[O-]C(=O)C1=CC=CC=C1 CLDWGXZGFUNWKB-UHFFFAOYSA-M 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- LRYRQGKGCIUVON-UHFFFAOYSA-N tert-butyl 4-(3-hydroxypropyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(CCCO)CC1 LRYRQGKGCIUVON-UHFFFAOYSA-N 0.000 description 1
- DQZZVXLHLNHTCF-UHFFFAOYSA-N tert-butyl 4-(5-methoxy-5-oxopentyl)-3-methylbenzoate Chemical compound COC(=O)CCCCC1=CC=C(C(=O)OC(C)(C)C)C=C1C DQZZVXLHLNHTCF-UHFFFAOYSA-N 0.000 description 1
- IMRJPWTUCBGZFU-UHFFFAOYSA-N tert-butyl 4-[2-(3-chloro-4-methoxycarbonylphenoxy)acetyl]piperazine-1-carboxylate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1OCC(=O)N1CCN(C(=O)OC(C)(C)C)CC1 IMRJPWTUCBGZFU-UHFFFAOYSA-N 0.000 description 1
- OVXVIECAAUSLTA-UHFFFAOYSA-N tert-butyl 4-[2-(4-methylphenyl)-2-oxoethyl]piperazine-1-carboxylate;1-(4-methylphenyl)-2-piperazin-1-ylethanone;dihydrochloride Chemical compound Cl.Cl.C1=CC(C)=CC=C1C(=O)CN1CCNCC1.C1=CC(C)=CC=C1C(=O)CN1CCN(C(=O)OC(C)(C)C)CC1 OVXVIECAAUSLTA-UHFFFAOYSA-N 0.000 description 1
- RIHBTHGKWXRWQX-UHFFFAOYSA-N tert-butyl 4-bromo-3-methylbenzoate Chemical compound CC1=CC(C(=O)OC(C)(C)C)=CC=C1Br RIHBTHGKWXRWQX-UHFFFAOYSA-N 0.000 description 1
- VEFYYBFRIFCCSE-UHFFFAOYSA-N tert-butyl N-[[4-(1,8-dimethyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)-2-fluorophenyl]methyl]carbamate Chemical compound Cc1ccc2N(Cc3cnn(C)c3Nc2c1)C(=O)c1ccc(CNC(=O)OC(C)(C)C)c(F)c1 VEFYYBFRIFCCSE-UHFFFAOYSA-N 0.000 description 1
- LYDRKKWPKKEMNZ-UHFFFAOYSA-N tert-butyl benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC=C1 LYDRKKWPKKEMNZ-UHFFFAOYSA-N 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- SRZQJMXVOPXEIL-UHFFFAOYSA-N tert-butyl n-[2-(cyclopropylmethylamino)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCNCC1CC1 SRZQJMXVOPXEIL-UHFFFAOYSA-N 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical class CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 210000000685 uterine artery Anatomy 0.000 description 1
- 230000008346 uterine blood flow Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 239000002536 vasopressin receptor antagonist Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D267/02—Seven-membered rings
- C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D267/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D267/14—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/08—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms with acylated ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
- C07D231/42—Benzene-sulfonamido pyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/06—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
- C07D233/08—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms with alkyl radicals, containing more than four carbon atoms, directly attached to ring carbon atoms
- C07D233/12—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms with alkyl radicals, containing more than four carbon atoms, directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D233/16—Radicals substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D267/02—Seven-membered rings
- C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D267/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D267/16—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with two six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/42—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms with nitro or nitroso radicals directly attached to ring carbon atoms
- C07D333/44—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms with nitro or nitroso radicals directly attached to ring carbon atoms attached in position 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Gynecology & Obstetrics (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Pregnancy & Childbirth (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Anesthesiology (AREA)
- Otolaryngology (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP04104062A EP1632494A1 (fr) | 2004-08-24 | 2004-08-24 | Antagonistes de la v1a vasopressine |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200701257B true ZA200701257B (en) | 2008-01-30 |
Family
ID=34929482
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200701257A ZA200701257B (en) | 2004-08-24 | 2007-02-12 | Vasopressin V10 antagonists |
Country Status (16)
Country | Link |
---|---|
US (2) | US8202858B2 (fr) |
EP (5) | EP1632494A1 (fr) |
JP (2) | JP4926058B2 (fr) |
KR (2) | KR20120047993A (fr) |
CN (2) | CN102617580B (fr) |
AT (1) | ATE557026T1 (fr) |
AU (4) | AU2005276790B2 (fr) |
BR (1) | BRPI0514661B8 (fr) |
CA (4) | CA2689274A1 (fr) |
ES (1) | ES2638114T3 (fr) |
IL (1) | IL178709A (fr) |
MX (1) | MX2007001392A (fr) |
NO (1) | NO20071560L (fr) |
RU (1) | RU2370497C2 (fr) |
WO (1) | WO2006021213A2 (fr) |
ZA (1) | ZA200701257B (fr) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2008251557B2 (en) | 2007-05-10 | 2012-12-06 | Albany Molecular Research, Inc. | Aryl- and heteroaryl-substituted tetrahydrobenzo-1,4-diazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
GB0804082D0 (en) * | 2008-03-04 | 2008-04-09 | Crysoptix Kk | Polycyclic organic compounds, polarizing elements and method of production t hereof |
GB0804083D0 (en) | 2008-03-04 | 2008-04-09 | Crysoptix Kk | Polycyclic organic compounds, retardation layer and compensation panel on their base |
WO2010027002A1 (fr) * | 2008-09-05 | 2010-03-11 | 塩野義製薬株式会社 | Derive de morpholine à cycles condensés ayant une activite inhibitrice de pi3k |
DK2356123T3 (da) | 2008-11-13 | 2012-10-15 | Hoffmann La Roche | Spiro-5,6-dihydro-4h-2,3,5,10b-tetraaza-benzo[e]azulener |
CN102216304B (zh) | 2008-11-18 | 2014-07-09 | 弗·哈夫曼-拉罗切有限公司 | 二氢四氮杂苯并薁的烷基环己基醚 |
RU2507205C2 (ru) | 2008-11-28 | 2014-02-20 | Ф. Хоффманн-Ля Рош Аг | Арилциклогексилэфиры дигидротетраазабензоазуленов для применения в качестве антагонистов рецептора вазопрессина v1a |
GB0903493D0 (en) * | 2009-02-27 | 2009-04-08 | Vantia Ltd | New compounds |
JP2011057661A (ja) * | 2009-08-14 | 2011-03-24 | Bayer Cropscience Ag | 殺虫性カルボキサミド類 |
JP5115762B2 (ja) * | 2010-02-12 | 2013-01-09 | 有機合成薬品工業株式会社 | 4−ホルミルピペリジンアセタール誘導体の製造方法 |
JP5187534B2 (ja) * | 2010-02-12 | 2013-04-24 | 有機合成薬品工業株式会社 | N−tert−ブトキシカルボニル−4−ホルミルピペリジンの製造方法 |
GB201004677D0 (en) * | 2010-03-19 | 2010-05-05 | Vantia Ltd | New salt |
US8420633B2 (en) | 2010-03-31 | 2013-04-16 | Hoffmann-La Roche Inc. | Aryl-cyclohexyl-tetraazabenzo[e]azulenes |
US8461151B2 (en) | 2010-04-13 | 2013-06-11 | Hoffmann-La Roche Inc. | Aryl-/heteroaryl-cyclohexenyl-tetraazabenzo[e]azulenes |
US8492376B2 (en) | 2010-04-21 | 2013-07-23 | Hoffmann-La Roche Inc. | Heteroaryl-cyclohexyl-tetraazabenzo[e]azulenes |
US8481528B2 (en) | 2010-04-26 | 2013-07-09 | Hoffmann-La Roche Inc. | Heterobiaryl-cyclohexyl-tetraazabenzo[e]azulenes |
US8513238B2 (en) | 2010-05-10 | 2013-08-20 | Hoffmann-La Roche Inc. | Heteroaryl-cyclohexyl-tetraazabenzo[E]azulenes |
ES2662350T3 (es) * | 2010-07-01 | 2018-04-06 | Azevan Pharmaceuticals, Inc. | Procedimientos para el tratamiento del trastorno por estrés postraumático |
BR112016022575A2 (pt) | 2014-03-28 | 2017-08-15 | Azevan Pharmaceuticals Inc | Composições e métodos para o tratamento de doenças neurodegenerativas |
US10086000B2 (en) | 2014-12-05 | 2018-10-02 | Merck Sharp & Dohme Corp. | Tricyclic compounds as inhibitors of mutant IDH enzymes |
WO2016089830A1 (fr) | 2014-12-05 | 2016-06-09 | Merck Sharp & Dohme Corp. | Nouveaux composés tricycliques utilisés en tant qu'inhibiteurs d'enzymes idh mutantes |
EP3226688B1 (fr) | 2014-12-05 | 2020-07-01 | Merck Sharp & Dohme Corp. | Composés tricycliques servant d'inhibiteurs d'enzymes idh mutantes |
CN104817487B (zh) * | 2015-05-06 | 2017-10-31 | 中国药科大学 | 一类可抑制表皮生长因子受体的哌啶基乙酰胺类化合物及其应用 |
EP3328864B1 (fr) | 2015-07-06 | 2022-09-07 | Kinoxis Therapeutics Pty Ltd | Composés et compositions thérapeutiques pour le traitement de troubles sociaux et de troubles liés à la toxicomanie |
KR102561721B1 (ko) * | 2016-12-12 | 2023-07-28 | 키녹시스 테라퓨틱스 피티와이 리미티드 | 비펩티드성 옥시토신 수용체 작용제 |
CN111295373A (zh) | 2017-09-15 | 2020-06-16 | 阿泽凡药物公司 | 用于治疗脑损伤的组合物和方法 |
TW201938171A (zh) | 2017-12-15 | 2019-10-01 | 匈牙利商羅特格登公司 | 作為血管升壓素V1a受體拮抗劑之三環化合物 |
HU231206B1 (hu) | 2017-12-15 | 2021-10-28 | Richter Gedeon Nyrt. | Triazolobenzazepinek |
GB201721960D0 (en) * | 2017-12-27 | 2018-02-07 | Bp Oil Int | Methods for preparing fuel additives |
JP2022547178A (ja) * | 2019-09-06 | 2022-11-10 | キノシス・セラピューティクス・ピーティーワイ・リミテッド | オピオイド離脱の治療 |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3960886A (en) * | 1968-07-03 | 1976-06-01 | Sterling Drug Inc. | Substituted N-arylanilines |
CA1047490A (fr) * | 1973-04-18 | 1979-01-30 | Friedrich Karrer | Ethers |
CH599752A5 (fr) | 1973-04-18 | 1978-05-31 | Ciba Geigy Ag | |
JPH0641455B2 (ja) * | 1984-12-10 | 1994-06-01 | 日産化学工業株式会社 | ピリダジノン誘導体 |
EP0189817A3 (fr) * | 1985-01-21 | 1987-04-22 | Fotofit Limited | Carte pliable utilisable comme carte de voeux ou carte de félicitations |
GB9307527D0 (en) * | 1993-04-13 | 1993-06-02 | Fujisawa Pharmaceutical Co | New venzamide derivatives,processes for the preparation thereof and pharmaceutical composition comprising the same |
US5516774A (en) | 1993-07-29 | 1996-05-14 | American Cyanamid Company | Tricyclic diazepine vasopressin antagonists and oxytocin antagonists |
US5843952A (en) * | 1993-07-29 | 1998-12-01 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
US5512563A (en) * | 1993-07-29 | 1996-04-30 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
US5760031A (en) * | 1993-07-29 | 1998-06-02 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
US5968930A (en) * | 1993-07-29 | 1999-10-19 | American Cyanamid Company | Tricyclic diazepine vasopressin antagonists and oxytocin antagonists |
PT1221440E (pt) | 1994-06-15 | 2007-07-20 | Otsuka Pharma Co Ltd | Derivados benzo-heterocíclicos úteis como moduladores da vasopressina ou oxitocina |
US5753648A (en) * | 1995-01-17 | 1998-05-19 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
US5536718A (en) * | 1995-01-17 | 1996-07-16 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
US5696112A (en) | 1995-01-17 | 1997-12-09 | American Cyanamid Company | Fused heterocyclic azepines as vasopressin antagonists |
GB9511694D0 (en) | 1995-06-09 | 1995-08-02 | Fujisawa Pharmaceutical Co | Benzamide derivatives |
AUPO395396A0 (en) * | 1996-12-02 | 1997-01-02 | Fujisawa Pharmaceutical Co., Ltd. | Benzamide derivatives |
US6583141B1 (en) * | 1998-10-09 | 2003-06-24 | Janssen Pharmaceutica, N.V. | 4,5-dihydro-isoxazole derivatives and their pharmaceutical use |
GB2355454A (en) * | 1999-10-20 | 2001-04-25 | Ferring Bv | Antidiuretic agents |
GB0015601D0 (en) * | 2000-06-26 | 2000-08-16 | Ferring Bv | Novel antidiuretic agents |
DE10033337A1 (de) * | 2000-07-08 | 2002-01-17 | Boehringer Ingelheim Pharma | Biphenylcarbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
GB0115515D0 (en) * | 2001-06-25 | 2001-08-15 | Ferring Bv | Oxytocin agonisys |
GB0120051D0 (en) * | 2001-08-16 | 2001-10-10 | Ferring Bv | Oxytocin agonists |
GB0224557D0 (en) * | 2002-10-22 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
EP1449844A1 (fr) * | 2003-02-14 | 2004-08-25 | Ferring B.V. | derives de benzamide agonistes de l'ocytocine et antagonistes de la vasopressine |
EP1512687A1 (fr) * | 2003-09-05 | 2005-03-09 | Ferring B.V. | Piperazines comme agonistes d'oxytocin |
EP1720836B1 (fr) | 2004-02-25 | 2014-04-16 | Eli Lilly And Company | 2,3,4,5-tetrahydro-1h-benzo [d]azepines substitues en position 6 en tant qu'agonistes de recepteur 5-ht sb 2c /sb |
EP1627876A1 (fr) | 2004-08-20 | 2006-02-22 | Ferring B.V. | Composés hétérocycliques condensés et leur usage et leur utilisation comme anti-diurétiques |
-
2004
- 2004-08-24 EP EP04104062A patent/EP1632494A1/fr not_active Withdrawn
-
2005
- 2005-08-24 CN CN201210100003.3A patent/CN102617580B/zh not_active Expired - Fee Related
- 2005-08-24 CA CA2689274A patent/CA2689274A1/fr not_active Abandoned
- 2005-08-24 AT AT10176766T patent/ATE557026T1/de active
- 2005-08-24 CA CA2688865A patent/CA2688865A1/fr not_active Abandoned
- 2005-08-24 RU RU2007101239/04A patent/RU2370497C2/ru not_active IP Right Cessation
- 2005-08-24 JP JP2007525172A patent/JP4926058B2/ja not_active Expired - Fee Related
- 2005-08-24 KR KR1020127005549A patent/KR20120047993A/ko not_active Application Discontinuation
- 2005-08-24 US US11/659,798 patent/US8202858B2/en active Active
- 2005-08-24 ES ES05773384.2T patent/ES2638114T3/es active Active
- 2005-08-24 CA CA2688912A patent/CA2688912A1/fr not_active Abandoned
- 2005-08-24 EP EP10176800A patent/EP2292621A1/fr not_active Withdrawn
- 2005-08-24 BR BRPI0514661A patent/BRPI0514661B8/pt not_active IP Right Cessation
- 2005-08-24 WO PCT/DK2005/000540 patent/WO2006021213A2/fr active Application Filing
- 2005-08-24 CN CNA2005800196904A patent/CN101563347A/zh active Pending
- 2005-08-24 KR KR1020097012993A patent/KR101155401B1/ko active IP Right Grant
- 2005-08-24 EP EP05773384.2A patent/EP1781661B1/fr active Active
- 2005-08-24 EP EP10176764A patent/EP2264037A1/fr not_active Withdrawn
- 2005-08-24 CA CA2567776A patent/CA2567776C/fr not_active Expired - Fee Related
- 2005-08-24 AU AU2005276790A patent/AU2005276790B2/en not_active Ceased
- 2005-08-24 MX MX2007001392A patent/MX2007001392A/es active IP Right Grant
- 2005-08-24 EP EP10176766A patent/EP2256119B1/fr active Active
-
2006
- 2006-10-18 IL IL178709A patent/IL178709A/en active IP Right Grant
-
2007
- 2007-02-12 ZA ZA200701257A patent/ZA200701257B/en unknown
- 2007-03-23 NO NO20071560A patent/NO20071560L/no not_active Application Discontinuation
-
2009
- 2009-03-24 AU AU2009201169A patent/AU2009201169B2/en not_active Ceased
- 2009-03-24 AU AU2009201167A patent/AU2009201167A1/en not_active Abandoned
- 2009-03-24 AU AU2009201168A patent/AU2009201168A1/en not_active Abandoned
-
2010
- 2010-07-26 JP JP2010167210A patent/JP2010285442A/ja active Pending
-
2011
- 2011-12-19 US US13/329,476 patent/US20120101082A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ZA200701257B (en) | Vasopressin V10 antagonists | |
DE60309913T2 (de) | BICYCLISCHE BENZAMIDVERBINDUNGEN ALS FüR DIE BEHANDLUNG NEUROLOGISCHER KRANKHEITEN GEEIGNETE HISTAMIN-H3-REZEPTORLIGANDEN | |
EP1554260A1 (fr) | Derives d'aryloxyalkylamine tels que des ligands du recepteur h3 | |
MXPA05004078A (es) | Piperazinas sustituidas, (1,4) diaszepinas y 2,5-diazabiciclo (2.2.1) heptanos como antagonistas de histamina h1 y/o h3 o antagonistas inversos de histamina h3. | |
AU2006236622A1 (en) | Compositions of novel opioid compounds and method of use thereof | |
DE2152282A1 (de) | Benzoxazin-,Benzothiazin- und Indolinonderivate und ihre pharmokologisch vertraeglichen Salze,Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneipraeparate | |
CA2368090A1 (fr) | Composes et procedes de traitement de l'asthme, des allergies et des maladies inflammatoires | |
US3908010A (en) | Basically substituted heterocycles as anti-emetics | |
JP4694747B2 (ja) | 二環式バソプレッシン・アゴニスト | |
Batt et al. | Vasopressin V 1a antagonists | |
KR20070032313A (ko) | 바소프레신 v1a 길항제 | |
AU747543B2 (en) | Process for converting propargylic amine-N-oxides to enaminones | |
US4022788A (en) | Indane tetrol amines | |
CA1066290A (fr) | Cyclitolamines |