CA1064029A - 2-substituted thio-1,4-benzodiazepine derivatives - Google Patents
2-substituted thio-1,4-benzodiazepine derivativesInfo
- Publication number
- CA1064029A CA1064029A CA222,537A CA222537A CA1064029A CA 1064029 A CA1064029 A CA 1064029A CA 222537 A CA222537 A CA 222537A CA 1064029 A CA1064029 A CA 1064029A
- Authority
- CA
- Canada
- Prior art keywords
- chloro
- benzodiazepine
- chlorophenyl
- give
- compound
- 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
- 238000000034 method Methods 0.000 claims abstract description 73
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 93
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 81
- -1 piperidino, 1-piperazinyl Chemical group 0.000 claims description 51
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 239000001530 fumaric acid Substances 0.000 claims description 26
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 14
- KFUPVMCNARYHKM-UHFFFAOYSA-N 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepine-2-thione Chemical compound C12=CC(Cl)=CC=C2NC(=S)CN=C1C1=CC=CC=C1Cl KFUPVMCNARYHKM-UHFFFAOYSA-N 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 11
- 231100000252 nontoxic Toxicity 0.000 claims description 11
- 230000003000 nontoxic effect Effects 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- ARYQUDZGCDBUOR-UHFFFAOYSA-N 2-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]-n,n-dimethylethanamine Chemical compound N=1CC(SCCN(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl ARYQUDZGCDBUOR-UHFFFAOYSA-N 0.000 claims description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 239000011976 maleic acid Substances 0.000 claims description 5
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 claims description 4
- JXTOHNBJLAXXAF-UHFFFAOYSA-N 3-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]-n,n-dimethylpropan-1-amine Chemical compound N=1CC(SCCCN(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl JXTOHNBJLAXXAF-UHFFFAOYSA-N 0.000 claims description 4
- FYFUOIDYPAGLQQ-UHFFFAOYSA-N 3-[[7-chloro-5-(2-methoxyphenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]-n,n-dimethylpropan-1-amine Chemical compound COC1=CC=CC=C1C1=NCC(SCCCN(C)C)=NC2=CC=C(Cl)C=C12 FYFUOIDYPAGLQQ-UHFFFAOYSA-N 0.000 claims description 4
- YPXQSGWOGQPLQO-UHFFFAOYSA-N 5-nitro-1,3-dihydrobenzimidazole-2-thione Chemical compound [O-][N+](=O)C1=CC=C2N=C(S)NC2=C1 YPXQSGWOGQPLQO-UHFFFAOYSA-N 0.000 claims description 4
- WVRKICIGIDTZIS-UHFFFAOYSA-N 6-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]-n,n-dimethylhexan-1-amine Chemical compound N=1CC(SCCCCCCN(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl WVRKICIGIDTZIS-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- VFLQQZCRHPIGJU-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine;hydron;chloride Chemical compound Cl.ClCCN1CCCCC1 VFLQQZCRHPIGJU-UHFFFAOYSA-N 0.000 claims description 3
- UDPWEHAXMGAMRC-UHFFFAOYSA-N 2-[[5-(2-chlorophenyl)-7-nitro-3h-1,4-benzodiazepin-2-yl]sulfanyl]-n,n-dimethylethanamine Chemical compound N=1CC(SCCN(C)C)=NC2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1Cl UDPWEHAXMGAMRC-UHFFFAOYSA-N 0.000 claims description 3
- ZTCNXMBSNSTSPC-UHFFFAOYSA-N 2-[[7-bromo-5-(2-fluorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]-n,n-dimethylethanamine Chemical compound N=1CC(SCCN(C)C)=NC2=CC=C(Br)C=C2C=1C1=CC=CC=C1F ZTCNXMBSNSTSPC-UHFFFAOYSA-N 0.000 claims description 3
- XROXLEJDIVPQGY-UHFFFAOYSA-N 2-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]-n,n-dimethylpropan-1-amine Chemical compound N=1CC(SC(CN(C)C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl XROXLEJDIVPQGY-UHFFFAOYSA-N 0.000 claims description 3
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 claims description 3
- QPYMREWYBUWOLY-UHFFFAOYSA-N 4-[2-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]ethyl]morpholine Chemical compound C12=CC(Cl)=CC=C2N=C(SCCN2CCOCC2)CN=C1C1=CC=CC=C1Cl QPYMREWYBUWOLY-UHFFFAOYSA-N 0.000 claims description 3
- XQPVPXSEPJHVPI-UHFFFAOYSA-N 4-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]-n,n-dimethylbutan-1-amine Chemical compound N=1CC(SCCCCN(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl XQPVPXSEPJHVPI-UHFFFAOYSA-N 0.000 claims description 3
- HOGVDODTPAJDHO-UHFFFAOYSA-N 7-chloro-5-(2-chlorophenyl)-2-(2-piperidin-1-ylethylsulfanyl)-3h-1,4-benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N=C(SCCN2CCCCC2)CN=C1C1=CC=CC=C1Cl HOGVDODTPAJDHO-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- YVIKKSJEWUDZQG-UHFFFAOYSA-N n,n-dimethyl-2-[(7-nitro-5-phenyl-3h-1,4-benzodiazepin-2-yl)sulfanyl]ethanamine Chemical compound N=1CC(SCCN(C)C)=NC2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1 YVIKKSJEWUDZQG-UHFFFAOYSA-N 0.000 claims description 3
- UYXGFVCZUIYSJZ-UHFFFAOYSA-N n-butyl-n-[2-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]ethyl]butan-1-amine Chemical compound N=1CC(SCCN(CCCC)CCCC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl UYXGFVCZUIYSJZ-UHFFFAOYSA-N 0.000 claims description 3
- UFRGXRPHKUXLIU-UHFFFAOYSA-N 1,4-benzodiazepine-2-thione Chemical class S=C1C=NC=C2C=CC=CC2=N1 UFRGXRPHKUXLIU-UHFFFAOYSA-N 0.000 claims description 2
- ZQDSOUPBYJIPNM-UHFFFAOYSA-N 1-(2-chloroethyl)azepane;hydrochloride Chemical compound [Cl-].ClCC[NH+]1CCCCCC1 ZQDSOUPBYJIPNM-UHFFFAOYSA-N 0.000 claims description 2
- GQEZLLGQUIRVHL-UHFFFAOYSA-N 1-(3-chloropropyl)azepane;hydrochloride Chemical compound Cl.ClCCCN1CCCCCC1 GQEZLLGQUIRVHL-UHFFFAOYSA-N 0.000 claims description 2
- UUPCYQIIQHSPKR-UHFFFAOYSA-N 1-(3-chloropropyl)pyrrolidine;hydrochloride Chemical compound Cl.ClCCCN1CCCC1 UUPCYQIIQHSPKR-UHFFFAOYSA-N 0.000 claims description 2
- OCWGRWAYARCRTQ-UHFFFAOYSA-N 2-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CC(Cl)CN(C)C OCWGRWAYARCRTQ-UHFFFAOYSA-N 0.000 claims description 2
- NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 claims description 2
- NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 claims description 2
- PQECODMSWJOUAT-UHFFFAOYSA-N 4-(3-chloropropyl)morpholine;hydrochloride Chemical compound [Cl-].ClCCC[NH+]1CCOCC1 PQECODMSWJOUAT-UHFFFAOYSA-N 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- ZPRUXOMHPKKNQD-UHFFFAOYSA-N n-(2-chloroethyl)-n-hexylhexan-1-amine Chemical compound CCCCCCN(CCCl)CCCCCC ZPRUXOMHPKKNQD-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 27
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 4
- 239000005977 Ethylene Substances 0.000 claims 4
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims 4
- MBMYRKRPLPRVJB-UHFFFAOYSA-N 10-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]-n,n-dimethyldecan-1-amine Chemical compound N=1CC(SCCCCCCCCCCN(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl MBMYRKRPLPRVJB-UHFFFAOYSA-N 0.000 claims 2
- OXADLBJZSCQWSX-UHFFFAOYSA-N 2-[2-(azepan-1-yl)ethylsulfanyl]-7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N=C(SCCN2CCCCCC2)CN=C1C1=CC=CC=C1Cl OXADLBJZSCQWSX-UHFFFAOYSA-N 0.000 claims 2
- DVRORPCOBSFUHR-UHFFFAOYSA-N 2-[3-(azepan-1-yl)propylsulfanyl]-7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N=C(SCCCN2CCCCCC2)CN=C1C1=CC=CC=C1Cl DVRORPCOBSFUHR-UHFFFAOYSA-N 0.000 claims 2
- WUNACBVZYMJZHV-UHFFFAOYSA-N 4-[3-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]propyl]morpholine Chemical compound C12=CC(Cl)=CC=C2N=C(SCCCN2CCOCC2)CN=C1C1=CC=CC=C1Cl WUNACBVZYMJZHV-UHFFFAOYSA-N 0.000 claims 2
- XUABZHOOKQODQO-UHFFFAOYSA-N 5-phenyl-2-(2-piperidin-1-ylethylsulfanyl)-7-(trifluoromethyl)-3h-1,4-benzodiazepine Chemical compound C12=CC(C(F)(F)F)=CC=C2N=C(SCCN2CCCCC2)CN=C1C1=CC=CC=C1 XUABZHOOKQODQO-UHFFFAOYSA-N 0.000 claims 2
- SBTSAOSCBJWICM-UHFFFAOYSA-N 7-chloro-2-[2-(4-methylpiperazin-1-yl)ethylsulfanyl]-5-phenyl-3h-1,4-benzodiazepine Chemical compound C1CN(C)CCN1CCSC1=NC2=CC=C(Cl)C=C2C(C=2C=CC=CC=2)=NC1 SBTSAOSCBJWICM-UHFFFAOYSA-N 0.000 claims 2
- OXPDLYYHOALIHL-UHFFFAOYSA-N 7-chloro-5-(2-chlorophenyl)-2-(2-pyrrolidin-1-ylethylsulfanyl)-3h-1,4-benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N=C(SCCN2CCCC2)CN=C1C1=CC=CC=C1Cl OXPDLYYHOALIHL-UHFFFAOYSA-N 0.000 claims 2
- JYMLLWZUZRMMEQ-UHFFFAOYSA-N 7-chloro-5-(2-chlorophenyl)-2-(3-piperidin-1-ylpropylsulfanyl)-3h-1,4-benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N=C(SCCCN2CCCCC2)CN=C1C1=CC=CC=C1Cl JYMLLWZUZRMMEQ-UHFFFAOYSA-N 0.000 claims 2
- GGGRQTVRLADMIK-UHFFFAOYSA-N 7-chloro-5-(2-chlorophenyl)-2-(3-pyrrolidin-1-ylpropylsulfanyl)-3h-1,4-benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N=C(SCCCN2CCCC2)CN=C1C1=CC=CC=C1Cl GGGRQTVRLADMIK-UHFFFAOYSA-N 0.000 claims 2
- LOJHNATXWNJDMZ-UHFFFAOYSA-N 7-chloro-5-(2-chlorophenyl)-2-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propylsulfanyl]-3h-1,4-benzodiazepine Chemical compound COC1=CC=CC=C1N1CCN(CCCSC=2CN=C(C3=CC(Cl)=CC=C3N=2)C=2C(=CC=CC=2)Cl)CC1 LOJHNATXWNJDMZ-UHFFFAOYSA-N 0.000 claims 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- GJEYGBOTTCHWMX-UHFFFAOYSA-N n-[2-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]ethyl]-n-hexylhexan-1-amine Chemical compound N=1CC(SCCN(CCCCCC)CCCCCC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl GJEYGBOTTCHWMX-UHFFFAOYSA-N 0.000 claims 2
- KQZFOKHEYIMXID-UHFFFAOYSA-N 1-(2-chloroethyl)-4-methylpiperazine;dihydrochloride Chemical compound Cl.Cl.CN1CCN(CCCl)CC1 KQZFOKHEYIMXID-UHFFFAOYSA-N 0.000 claims 1
- FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 claims 1
- VXUOGWKMOXFLHN-UHFFFAOYSA-N 1-(3-chloropropyl)-4-(2-methoxyphenyl)piperazine;hydrochloride Chemical compound Cl.COC1=CC=CC=C1N1CCN(CCCCl)CC1 VXUOGWKMOXFLHN-UHFFFAOYSA-N 0.000 claims 1
- GYXWNSDLDXGMGU-UHFFFAOYSA-N 2-chloro-n,n-dimethylpropan-1-amine Chemical compound CC(Cl)CN(C)C GYXWNSDLDXGMGU-UHFFFAOYSA-N 0.000 claims 1
- LYHKQHLOZUTVKA-UHFFFAOYSA-N 4-chloro-n,n-dimethylbutan-1-amine Chemical compound CN(C)CCCCCl LYHKQHLOZUTVKA-UHFFFAOYSA-N 0.000 claims 1
- IZYKFSZYKIUTTE-UHFFFAOYSA-N 5-(2-chlorophenyl)-7-nitro-1,3-dihydro-1,4-benzodiazepine-2-thione Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=S)CN=C1C1=CC=CC=C1Cl IZYKFSZYKIUTTE-UHFFFAOYSA-N 0.000 claims 1
- HVDVDGGJUWKUJB-UHFFFAOYSA-N 6-chloro-n,n-dimethylhexan-1-amine Chemical compound CN(C)CCCCCCCl HVDVDGGJUWKUJB-UHFFFAOYSA-N 0.000 claims 1
- USUIXVFPXJFJOO-UHFFFAOYSA-N 7-bromo-5-(2-fluorophenyl)-2,3-dihydro-1h-1,4-benzodiazepine Chemical compound FC1=CC=CC=C1C1=NCCNC2=CC=C(Br)C=C12 USUIXVFPXJFJOO-UHFFFAOYSA-N 0.000 claims 1
- BZSKBQKROZUHCC-UHFFFAOYSA-N 7-chloro-5-(2-chlorophenyl)-2,3-dihydro-1h-1,4-benzodiazepine Chemical compound C12=CC(Cl)=CC=C2NCCN=C1C1=CC=CC=C1Cl BZSKBQKROZUHCC-UHFFFAOYSA-N 0.000 claims 1
- QIQUHZGJGFZDLS-UHFFFAOYSA-N 7-chloro-5-(2-methoxyphenyl)-1,3-dihydro-1,4-benzodiazepine-2-thione Chemical compound ClC=1C=CC2=C(C(=NCC(N2)=S)C2=C(C=CC=C2)OC)C1 QIQUHZGJGFZDLS-UHFFFAOYSA-N 0.000 claims 1
- GEAUJEFXEUWJQP-UHFFFAOYSA-N 7-nitro-5-phenyl-1,3-dihydro-1,4-benzodiazepine-2-thione Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=S)CN=C1C1=CC=CC=C1 GEAUJEFXEUWJQP-UHFFFAOYSA-N 0.000 claims 1
- 229940125782 compound 2 Drugs 0.000 claims 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims 1
- GWHSVFQLPXJHBX-UHFFFAOYSA-N n-butyl-n-(2-chloroethyl)butan-1-amine Chemical compound CCCCN(CCCl)CCCC GWHSVFQLPXJHBX-UHFFFAOYSA-N 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims 1
- 230000000506 psychotropic effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- 239000000203 mixture Substances 0.000 description 39
- 239000000243 solution Substances 0.000 description 39
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
- 239000002904 solvent Substances 0.000 description 29
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 16
- 229960003390 magnesium sulfate Drugs 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 235000002639 sodium chloride Nutrition 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 239000011877 solvent mixture Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 238000004821 distillation Methods 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 235000013350 formula milk Nutrition 0.000 description 8
- 229960004592 isopropanol Drugs 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
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- 229940022682 acetone Drugs 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
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- 125000001424 substituent group Chemical group 0.000 description 6
- 239000000725 suspension Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
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- 235000019441 ethanol Nutrition 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
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- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 2
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
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- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
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- 235000001055 magnesium Nutrition 0.000 description 2
- 229940091250 magnesium supplement Drugs 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
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- 239000011734 sodium Substances 0.000 description 2
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- 230000002936 tranquilizing effect Effects 0.000 description 2
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- KSUXXTYEHZDRDK-WLHGVMLRSA-N (e)-but-2-enedioic acid;4-[3-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]propyl]morpholine Chemical compound OC(=O)\C=C\C(O)=O.C12=CC(Cl)=CC=C2N=C(SCCCN2CCOCC2)CN=C1C1=CC=CC=C1Cl KSUXXTYEHZDRDK-WLHGVMLRSA-N 0.000 description 1
- GVOKDVLKNDNQLY-WLHGVMLRSA-N (e)-but-2-enedioic acid;7-chloro-5-(2-chlorophenyl)-2-(2-piperidin-1-ylethylsulfanyl)-3h-1,4-benzodiazepine Chemical compound OC(=O)\C=C\C(O)=O.C12=CC(Cl)=CC=C2N=C(SCCN2CCCCC2)CN=C1C1=CC=CC=C1Cl GVOKDVLKNDNQLY-WLHGVMLRSA-N 0.000 description 1
- ZQWOMVVVPCGFHR-WLHGVMLRSA-N (e)-but-2-enedioic acid;7-chloro-5-(2-chlorophenyl)-2-(3-piperidin-1-ylpropylsulfanyl)-3h-1,4-benzodiazepine Chemical compound OC(=O)\C=C\C(O)=O.C12=CC(Cl)=CC=C2N=C(SCCCN2CCCCC2)CN=C1C1=CC=CC=C1Cl ZQWOMVVVPCGFHR-WLHGVMLRSA-N 0.000 description 1
- GFGQMEZSKAQPQP-BTJKTKAUSA-N (z)-but-2-enedioic acid;2-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]sulfanyl]-n,n-dimethylethanamine Chemical compound OC(=O)\C=C/C(O)=O.N=1CC(SCCN(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl GFGQMEZSKAQPQP-BTJKTKAUSA-N 0.000 description 1
- YQVIKSSPDSGBRH-BTJKTKAUSA-N (z)-but-2-enedioic acid;n,n-dimethyl-2-[(7-nitro-5-phenyl-3h-1,4-benzodiazepin-2-yl)sulfanyl]ethanamine Chemical compound OC(=O)\C=C/C(O)=O.N=1CC(SCCN(C)C)=NC2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1 YQVIKSSPDSGBRH-BTJKTKAUSA-N 0.000 description 1
- OBOBUDMMFXRNDO-UHFFFAOYSA-N 1-(3-chloropropyl)piperidine;hydron;chloride Chemical compound Cl.ClCCCN1CCCCC1 OBOBUDMMFXRNDO-UHFFFAOYSA-N 0.000 description 1
- OEUPQULTDYTGGS-UHFFFAOYSA-N 1-ethylpyrrolidin-1-ium;chloride Chemical compound Cl.CCN1CCCC1 OEUPQULTDYTGGS-UHFFFAOYSA-N 0.000 description 1
- WGWNCURHUGWTQY-WLHGVMLRSA-N 2-[3-(azepan-1-yl)propylsulfanyl]-7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepine;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C12=CC(Cl)=CC=C2N=C(SCCCN2CCCCCC2)CN=C1C1=CC=CC=C1Cl WGWNCURHUGWTQY-WLHGVMLRSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- LJQNMDZRCXJETK-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CN(C)CCCCl LJQNMDZRCXJETK-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- XTLNYNMNUCLWEZ-UHFFFAOYSA-N ethanol;propan-2-one Chemical compound CCO.CC(C)=O XTLNYNMNUCLWEZ-UHFFFAOYSA-N 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- CHDFNIZLAAFFPX-UHFFFAOYSA-N ethoxyethane;oxolane Chemical compound CCOCC.C1CCOC1 CHDFNIZLAAFFPX-UHFFFAOYSA-N 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940112041 peripherally acting muscle relaxants other quaternary ammonium compound in atc Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- UMSVPCYSAUKCAZ-UHFFFAOYSA-N propane;hydrochloride Chemical compound Cl.CCC UMSVPCYSAUKCAZ-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/22—Sulfur atoms
-
- 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
- A61P25/20—Hypnotics; Sedatives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Anesthesiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49031905A JPS5919099B2 (ja) | 1974-03-20 | 1974-03-20 | ２−置換チオ−１，４−ベンゾジアゼピン誘導体の製造法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1064029A true CA1064029A (en) | 1979-10-09 |
Family
ID=12344003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA222,537A Expired CA1064029A (en) | 1974-03-20 | 1975-03-19 | 2-substituted thio-1,4-benzodiazepine derivatives |
Country Status (15)
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4094870A (en) * | 1974-03-20 | 1978-06-13 | Fujisawa Pharmaceutical Co., Ltd. | 2-Substituted thio-1,4-benzodiazepine derivatives |
| HU224435B1 (hu) * | 1995-02-09 | 2005-10-28 | EGIS Gyógyszergyár Rt. | Benzodiazepin-származékok, eljárás előállításukra, alkalmazásukra és ezeket tartalmazó gyógyászati készítmények |
-
1974
- 1974-03-20 JP JP49031905A patent/JPS5919099B2/ja not_active Expired
-
1975
- 1975-03-18 BE BE154448A patent/BE826817A/xx unknown
- 1975-03-18 HU HUFU333A patent/HU170141B/hu unknown
- 1975-03-19 CA CA222,537A patent/CA1064029A/en not_active Expired
- 1975-03-19 SE SE7503164A patent/SE7503164L/xx unknown
- 1975-03-19 DK DK114175A patent/DK114175A/da unknown
- 1975-03-19 NO NO750943A patent/NO750943L/no unknown
- 1975-03-19 FI FI750816A patent/FI750816A7/fi not_active Application Discontinuation
- 1975-03-19 ZA ZA00751715A patent/ZA751715B/xx unknown
- 1975-03-19 GB GB1151875A patent/GB1467763A/en not_active Expired
- 1975-03-19 AU AU79298/75A patent/AU7929875A/en not_active Expired
- 1975-03-19 NL NL7503269A patent/NL7503269A/xx unknown
- 1975-03-19 DE DE19752511898 patent/DE2511898A1/de not_active Withdrawn
- 1975-03-19 FR FR7508599A patent/FR2264545B1/fr not_active Expired
- 1975-03-20 ES ES435812A patent/ES435812A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE2511898A1 (de) | 1975-09-25 |
| NL7503269A (nl) | 1975-09-23 |
| HU170141B (enrdf_load_stackoverflow) | 1977-04-28 |
| ZA751715B (en) | 1976-02-25 |
| BE826817A (fr) | 1975-09-18 |
| FR2264545A1 (enrdf_load_stackoverflow) | 1975-10-17 |
| NO750943L (enrdf_load_stackoverflow) | 1975-09-23 |
| GB1467763A (en) | 1977-03-23 |
| FR2264545B1 (enrdf_load_stackoverflow) | 1978-08-04 |
| SE7503164L (enrdf_load_stackoverflow) | 1975-09-22 |
| AU7929875A (en) | 1976-09-23 |
| JPS5919099B2 (ja) | 1984-05-02 |
| FI750816A7 (enrdf_load_stackoverflow) | 1975-09-21 |
| ES435812A1 (es) | 1976-12-01 |
| DK114175A (enrdf_load_stackoverflow) | 1975-09-21 |
| JPS50131980A (enrdf_load_stackoverflow) | 1975-10-18 |
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