CA1043784A - Triazolo-benzodiazepines - Google Patents
Triazolo-benzodiazepinesInfo
- Publication number
- CA1043784A CA1043784A CA220,506A CA220506A CA1043784A CA 1043784 A CA1043784 A CA 1043784A CA 220506 A CA220506 A CA 220506A CA 1043784 A CA1043784 A CA 1043784A
- Authority
- CA
- Canada
- Prior art keywords
- triazolo
- benzodiazepine
- chloro
- phenyl
- bromo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 229940049706 benzodiazepine Drugs 0.000 title abstract description 41
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 31
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- 239000001257 hydrogen Substances 0.000 claims abstract description 21
- 239000002253 acid Substances 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract 3
- 238000000034 method Methods 0.000 claims description 16
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical group CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims description 6
- 239000000376 reactant Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- LRYQLZPLLLLXFG-UHFFFAOYSA-N 2-[4-(8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)piperazin-1-yl]ethanol Chemical group C1CN(CCO)CCN1C1=NN=C2N1C1=CC=C(Cl)C=C1C(C=1C=CC=CC=1)=NC2 LRYQLZPLLLLXFG-UHFFFAOYSA-N 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- AGWVSOABLRBASB-UHFFFAOYSA-N 8-chloro-6-phenyl-1-piperazin-1-yl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(Cl)=CC=C(N23)C=1C(C=1C=CC=CC=1)=NCC3=NN=C2N1CCNCC1 AGWVSOABLRBASB-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 6
- 239000000126 substance Substances 0.000 claims 4
- OQTNBOMJLUEWDM-UHFFFAOYSA-N 1-bromo-8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(Cl)=CC=C(N2C(Br)=NN=C2CN=2)C=1C=2C1=CC=CC=C1 OQTNBOMJLUEWDM-UHFFFAOYSA-N 0.000 claims 3
- CDXVRKYAZPDCRX-UHFFFAOYSA-N 8-chloro-1-(4-methylpiperazin-1-yl)-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical group C1CN(C)CCN1C1=NN=C2N1C1=CC=C(Cl)C=C1C(C=1C=CC=CC=1)=NC2 CDXVRKYAZPDCRX-UHFFFAOYSA-N 0.000 claims 2
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 241000124008 Mammalia Species 0.000 abstract description 5
- 208000019901 Anxiety disease Diseases 0.000 abstract description 3
- 230000001430 anti-depressive effect Effects 0.000 abstract description 3
- 230000036506 anxiety Effects 0.000 abstract description 3
- 230000002936 tranquilizing effect Effects 0.000 abstract description 3
- 150000001557 benzodiazepines Chemical class 0.000 abstract description 2
- 230000001624 sedative effect Effects 0.000 abstract description 2
- 239000000932 sedative agent Substances 0.000 abstract 1
- 230000001629 suppression Effects 0.000 abstract 1
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 61
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 34
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 13
- 229960005141 piperazine Drugs 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 11
- 230000008018 melting Effects 0.000 description 10
- 238000002844 melting Methods 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 229950005499 carbon tetrachloride Drugs 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- JTJIKSLNZSETFL-UHFFFAOYSA-N 1,8-dibromo-6-(2-chlorophenyl)-7-(trifluoromethyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound BrC1=NN=C2N1C1=C(C(=NC2)C2=C(C=CC=C2)Cl)C(=C(C=C1)Br)C(F)(F)F JTJIKSLNZSETFL-UHFFFAOYSA-N 0.000 description 3
- ZDNVTCJLKWHMOV-UHFFFAOYSA-N 1-bromo-8-chloro-6-(2-nitrophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound BrC1=NN=C2N1C1=C(C(=NC2)C2=C(C=CC=C2)[N+](=O)[O-])C=C(C=C1)Cl ZDNVTCJLKWHMOV-UHFFFAOYSA-N 0.000 description 3
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- NJPPVKZQTLUDBO-UHFFFAOYSA-N novaluron Chemical compound C1=C(Cl)C(OC(F)(F)C(OC(F)(F)F)F)=CC=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F NJPPVKZQTLUDBO-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229960001866 silicon dioxide Drugs 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000012258 stirred mixture Substances 0.000 description 3
- BSAXMXULFWQQCZ-UHFFFAOYSA-N 1-bromo-6-phenyl-8-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(C(F)(F)F)=CC=C(N2C(Br)=NN=C2CN=2)C=1C=2C1=CC=CC=C1 BSAXMXULFWQQCZ-UHFFFAOYSA-N 0.000 description 2
- GLAOZTQZKRZWBW-UHFFFAOYSA-N 1-bromo-8-chloro-6-(2-fluorophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound FC1=CC=CC=C1C1=NCC2=NN=C(Br)N2C2=CC=C(Cl)C=C12 GLAOZTQZKRZWBW-UHFFFAOYSA-N 0.000 description 2
- DAFHCONKMBUFLL-UHFFFAOYSA-N 1-bromo-8-nitro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C([N+](=O)[O-])=CC=C(N2C(Br)=NN=C2CN=2)C=1C=2C1=CC=CC=C1 DAFHCONKMBUFLL-UHFFFAOYSA-N 0.000 description 2
- LKRNZLYYWVHIFZ-UHFFFAOYSA-N 4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C1N=CC2=CC=CC=C2N2C=NN=C12 LKRNZLYYWVHIFZ-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 2
- 235000011613 Pinus brutia Nutrition 0.000 description 2
- 241000018646 Pinus brutia Species 0.000 description 2
- 239000000538 analytical sample Substances 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical class OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- CDCHDCWJMGXXRH-UHFFFAOYSA-N estazolam Chemical compound C=1C(Cl)=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=CC=C1 CDCHDCWJMGXXRH-UHFFFAOYSA-N 0.000 description 2
- -1 ethyl acetate-Skellysolve B hexanes Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- KDDIEMOTUOHMMQ-UHFFFAOYSA-N 1,8-dibromo-6-(2-methylphenyl)-9-nitro-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound BrC1=NN=C2N1C1=C(C(=NC2)C2=C(C=CC=C2)C)C=C(C(=C1)[N+](=O)[O-])Br KDDIEMOTUOHMMQ-UHFFFAOYSA-N 0.000 description 1
- YHQNFIZIFDXVDS-UHFFFAOYSA-N 1,8-dibromo-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(Br)=CC=C2N2C(Br)=NN=C2CN=C1C1=CC=CC=C1 YHQNFIZIFDXVDS-UHFFFAOYSA-N 0.000 description 1
- KMMQCBBUBSDWQW-UHFFFAOYSA-N 1-(4-methylpiperazin-1-yl)-6-phenyl-8-(trifluoromethyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound FC(C=1C=CC2=C(C(=NCC=3N2C(=NN3)N3CCN(CC3)C)C3=CC=CC=C3)C1)(F)F KMMQCBBUBSDWQW-UHFFFAOYSA-N 0.000 description 1
- YDTPKYQMPTVFLW-UHFFFAOYSA-N 1-(4-methylpiperazin-1-yl)-8-nitro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=NCC=3N2C(=NN3)N3CCN(CC3)C)C3=CC=CC=C3)C1 YDTPKYQMPTVFLW-UHFFFAOYSA-N 0.000 description 1
- CFUDDZFFAXUTHN-UHFFFAOYSA-N 1-bromo-4-ethyl-8-fluoro-6-(4-nitrophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound BrC1=NN=C2N1C1=C(C(=NC2CC)C2=CC=C(C=C2)[N+](=O)[O-])C=C(C=C1)F CFUDDZFFAXUTHN-UHFFFAOYSA-N 0.000 description 1
- HSICKRDGVHLSMM-UHFFFAOYSA-N 1-bromo-8-chloro-6-(2-chlorophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(Cl)=CC=C(N2C(Br)=NN=C2CN=2)C=1C=2C1=CC=CC=C1Cl HSICKRDGVHLSMM-UHFFFAOYSA-N 0.000 description 1
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 1
- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 1
- QLEIDMAURCRVCX-UHFFFAOYSA-N 1-propylpiperazine Chemical compound CCCN1CCNCC1 QLEIDMAURCRVCX-UHFFFAOYSA-N 0.000 description 1
- LGNWUMGEJQAWQD-UHFFFAOYSA-N 1h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound N1=CC2=CC=CC=C2N2CN=NC2=C1 LGNWUMGEJQAWQD-UHFFFAOYSA-N 0.000 description 1
- MCCFXZWKGRAAFH-UHFFFAOYSA-N 2-[4-[8-bromo-6-(2-chlorophenyl)-7-(trifluoromethyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]piperazin-1-yl]ethanol Chemical compound BrC=1C=CC2=C(C(=NCC=3N2C(=NN3)N3CCN(CC3)CCO)C3=C(C=CC=C3)Cl)C1C(F)(F)F MCCFXZWKGRAAFH-UHFFFAOYSA-N 0.000 description 1
- SGZQKRBNZQSRDA-UHFFFAOYSA-N 2-[4-[8-chloro-6-(2-chlorophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]piperazin-1-yl]ethanol Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C(=NN3)N3CCN(CC3)CCO)C3=C(C=CC=C3)Cl)C1 SGZQKRBNZQSRDA-UHFFFAOYSA-N 0.000 description 1
- VGZMLAZJYXQHTH-UHFFFAOYSA-N 2-[4-[8-chloro-6-(2-fluorophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]piperazin-1-yl]ethanol Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C(=NN3)N3CCN(CC3)CCO)C3=C(C=CC=C3)F)C1 VGZMLAZJYXQHTH-UHFFFAOYSA-N 0.000 description 1
- RSKVYLJDIVMZMK-UHFFFAOYSA-N 2-[4-[8-chloro-6-(2-nitrophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]piperazin-1-yl]ethanol Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C(=NN3)N3CCN(CC3)CCO)C3=C(C=CC=C3)[N+](=O)[O-])C1 RSKVYLJDIVMZMK-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- LZANARFQFSEWHV-UHFFFAOYSA-N 5-phenyl-1,3-dihydro-1,4-benzodiazepine-2-thione Chemical class C12=CC=CC=C2NC(=S)CN=C1C1=CC=CC=C1 LZANARFQFSEWHV-UHFFFAOYSA-N 0.000 description 1
- NALCCYALPDNKNJ-UHFFFAOYSA-N 6-(2-chlorophenyl)-1-(4-methylpiperazin-1-yl)-8-nitro-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=NCC=3N2C(=NN3)N3CCN(CC3)C)C3=C(C=CC=C3)Cl)C1 NALCCYALPDNKNJ-UHFFFAOYSA-N 0.000 description 1
- JMWUOISVZISQHD-UHFFFAOYSA-N 6-(3-bromophenyl)-9-fluoro-4-methyl-1-(4-methylpiperazin-1-yl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound FC1=CC2=C(C(=NC(C=3N2C(=NN3)N3CCN(CC3)C)C)C3=CC(=CC=C3)Br)C=C1 JMWUOISVZISQHD-UHFFFAOYSA-N 0.000 description 1
- HCCOBJRHGYBXIQ-UHFFFAOYSA-N 6-phenyl-1-piperazin-1-yl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical class C1CNCCN1C1=NN=C2N1C1=CC=CC=C1C(C=1C=CC=CC=1)=NC2 HCCOBJRHGYBXIQ-UHFFFAOYSA-N 0.000 description 1
- AWGQOFJFINCCTK-UHFFFAOYSA-N 7,10-dichloro-1-(4-methylpiperazin-1-yl)-6-(3-nitrophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound ClC1=CC=C(C2=C1C(=NCC=1N2C(=NN1)N1CCN(CC1)C)C1=CC(=CC=C1)[N+](=O)[O-])Cl AWGQOFJFINCCTK-UHFFFAOYSA-N 0.000 description 1
- ULILTJWAJZIROM-UHFFFAOYSA-N 7-chloro-5-phenyl-1,3-dihydro-1,4-benzodiazepine-2-thione Chemical compound C12=CC(Cl)=CC=C2NC(=S)CN=C1C1=CC=CC=C1 ULILTJWAJZIROM-UHFFFAOYSA-N 0.000 description 1
- PDBJXNIYCDILSJ-UHFFFAOYSA-N 8-bromo-6-(2-chlorophenyl)-1-(4-propylpiperazin-1-yl)-7-(trifluoromethyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound BrC=1C=CC2=C(C(=NCC=3N2C(=NN3)N3CCN(CC3)CCC)C3=C(C=CC=C3)Cl)C1C(F)(F)F PDBJXNIYCDILSJ-UHFFFAOYSA-N 0.000 description 1
- PQGWNSHSNSISRC-UHFFFAOYSA-N 8-chloro-1-(4-methylpiperazin-1-yl)-6-(2-nitrophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C(=NN3)N3CCN(CC3)C)C3=C(C=CC=C3)[N+](=O)[O-])C1 PQGWNSHSNSISRC-UHFFFAOYSA-N 0.000 description 1
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- IHFGWBOFMSDOHF-UHFFFAOYSA-N 8-chloro-6-(2-nitrophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C=NN3)C3=C(C=CC=C3)[N+](=O)[O-])C1 IHFGWBOFMSDOHF-UHFFFAOYSA-N 0.000 description 1
- MBWHYICJBGVYJE-UHFFFAOYSA-N 8-nitro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C([N+](=O)[O-])=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=CC=C1 MBWHYICJBGVYJE-UHFFFAOYSA-N 0.000 description 1
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
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- RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 240000003461 Setaria viridis Species 0.000 description 1
- 235000002248 Setaria viridis Nutrition 0.000 description 1
- 235000010086 Setaria viridis var. viridis Nutrition 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 240000002439 Sorghum halepense Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 150000004908 diazepines Chemical class 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000035929 gnawing Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229940125725 tranquilizer Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 229940055764 triaz Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical class OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- GQDDNDAYOVNZPG-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C[C]2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3N=C21 GQDDNDAYOVNZPG-SCYLSFHTSA-N 0.000 description 1
- 229960000317 yohimbine Drugs 0.000 description 1
- AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Fodder In General (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US453195A US3894025A (en) | 1974-03-21 | 1974-03-21 | 1-Piperazino-6-phenyl-4H-s-triazolo{8 4,3-a{9 {8 1,4{9 -benzodiazepine compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1043784A true CA1043784A (en) | 1978-12-05 |
Family
ID=23799556
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA220,506A Expired CA1043784A (en) | 1974-03-21 | 1975-02-20 | Triazolo-benzodiazepines |
Country Status (10)
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3996230A (en) * | 1975-03-28 | 1976-12-07 | The Upjohn Company | 1-Piperazino-6-(2-pyridyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepines |
| FI63033C (fi) * | 1977-07-21 | 1983-04-11 | Boehringer Sohn Ingelheim | Foerfarande foer framstaellning av anxiolytiska tranquilliserande sedativa och/eller neuroleptiska substituerade 1-piperazinyl-4h-s-triazolo(3,4-c)tieno(2,3-e)-1,4-diazepiner |
| US4455307A (en) * | 1982-01-04 | 1984-06-19 | The Upjohn Company | Antihypertensive use of triazolobenzodiazepines |
| US4472397A (en) * | 1983-02-18 | 1984-09-18 | The Upjohn Company | Use of certain 1-substituted-triazolo-benzodiazepines to treat psychoses |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4932874B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1970-12-11 | 1974-09-03 | ||
| US3709899A (en) * | 1971-04-28 | 1973-01-09 | Upjohn Co | 6-phenyl-4h-s-triazolo(4,3-a)(1,4)benzodiazepines and their production |
| US3751426A (en) * | 1971-04-28 | 1973-08-07 | Upjohn Co | 1-substituted-6-phenyl-4h-s-triazolo(4,3-a)(1,6)benzodiazepine compounds |
| US3759943A (en) * | 1971-04-28 | 1973-09-18 | Upjohn Co | Amido and amino triazolo benzodiazepines |
| GB1323277A (en) * | 1971-05-10 | 1973-07-11 | Upjohn Co | Triazolobenzodiazepines |
-
1974
- 1974-03-21 US US453195A patent/US3894025A/en not_active Expired - Lifetime
-
1975
- 1975-02-14 CH CH180575A patent/CH599174A5/xx not_active IP Right Cessation
- 1975-02-20 CA CA220,506A patent/CA1043784A/en not_active Expired
- 1975-02-25 GB GB774975A patent/GB1431259A/en not_active Expired
- 1975-02-28 ZA ZA00751280A patent/ZA751280B/xx unknown
- 1975-03-05 NL NL7502581A patent/NL7502581A/xx unknown
- 1975-03-05 DE DE19752509456 patent/DE2509456A1/de not_active Withdrawn
- 1975-03-20 JP JP50034268A patent/JPS50129598A/ja active Pending
- 1975-03-20 FR FR7508797A patent/FR2264548B1/fr not_active Expired
- 1975-03-21 BE BE154589A patent/BE826986A/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| BE826986A (fr) | 1975-09-22 |
| DE2509456A1 (de) | 1975-09-25 |
| JPS50129598A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1975-10-13 |
| AU7909775A (en) | 1976-09-16 |
| ZA751280B (en) | 1976-01-28 |
| CH599174A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1978-05-12 |
| FR2264548A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1975-10-17 |
| US3894025A (en) | 1975-07-08 |
| NL7502581A (nl) | 1975-09-23 |
| FR2264548B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1978-07-28 |
| GB1431259A (en) | 1976-04-07 |
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