JPS6310698B2 - - Google Patents
Info
- Publication number
- JPS6310698B2 JPS6310698B2 JP53147316A JP14731678A JPS6310698B2 JP S6310698 B2 JPS6310698 B2 JP S6310698B2 JP 53147316 A JP53147316 A JP 53147316A JP 14731678 A JP14731678 A JP 14731678A JP S6310698 B2 JPS6310698 B2 JP S6310698B2
- Authority
- JP
- Japan
- Prior art keywords
- benzodiazepine
- formula
- methyl
- phenyl
- dihydro
- 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
- 150000001875 compounds Chemical class 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 25
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- -1 trifluoromethyl phenyl Chemical group 0.000 claims description 12
- 229960000583 acetic acid Drugs 0.000 claims description 10
- 229940117975 chromium trioxide Drugs 0.000 claims description 10
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims description 10
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 150000001557 benzodiazepines Chemical class 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 239000003929 acidic solution Substances 0.000 claims description 7
- 239000012458 free base Substances 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 239000012362 glacial acetic acid Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- UQZIVIVFXNMLLC-UHFFFAOYSA-N 2h-1,4-benzodiazepine Chemical compound C1C=NC=C2C=CC=CC2=N1 UQZIVIVFXNMLLC-UHFFFAOYSA-N 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 230000036506 anxiety Effects 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 3
- DZPMZHAPZCLHND-UHFFFAOYSA-N 2-[7-chloro-1-methyl-5-[2-(trifluoromethyl)phenyl]-3h-1,4-benzodiazepin-2-ylidene]acetamide Chemical compound N=1CC(=CC(N)=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1C(F)(F)F DZPMZHAPZCLHND-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims description 3
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical compound [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- ASFHFGRXOVTHQB-UHFFFAOYSA-N 2-[7-bromo-1-methyl-5-[2-(trifluoromethyl)phenyl]-3h-1,4-benzodiazepin-2-ylidene]acetamide Chemical compound N=1CC(=CC(N)=O)N(C)C2=CC=C(Br)C=C2C=1C1=CC=CC=C1C(F)(F)F ASFHFGRXOVTHQB-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 4
- NSGCECVNIHAAIE-UHFFFAOYSA-N 2,3-dihydro-1h-1,4-benzodiazepine Chemical compound N1CCN=CC2=CC=CC=C21 NSGCECVNIHAAIE-UHFFFAOYSA-N 0.000 claims 2
- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 claims 2
- 235000019260 propionic acid Nutrition 0.000 claims 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
- 206010039897 Sedation Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000036280 sedation Effects 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 238000002844 melting Methods 0.000 description 16
- 230000008018 melting Effects 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 8
- 230000001773 anti-convulsant effect Effects 0.000 description 7
- 229940049706 benzodiazepine Drugs 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 206010010904 Convulsion Diseases 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000012286 potassium permanganate Substances 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- RGGLEJFUEMKQSH-UHFFFAOYSA-N 1,4-benzodiazepin-2-one Chemical class O=C1C=NC=C2C=CC=CC2=N1 RGGLEJFUEMKQSH-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- ZSKVIRSEFWDRGE-UHFFFAOYSA-N 2-[7-chloro-5-(2-chlorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-ylidene]acetonitrile Chemical compound N=1CC(=CC#N)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl ZSKVIRSEFWDRGE-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 230000016571 aggressive behavior Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 208000012802 recumbency Diseases 0.000 description 3
- 230000001624 sedative effect Effects 0.000 description 3
- 229940125725 tranquilizer Drugs 0.000 description 3
- 239000003204 tranquilizing agent Substances 0.000 description 3
- 230000002936 tranquilizing effect Effects 0.000 description 3
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
- RFRJZWOCMUTXJR-UHFFFAOYSA-N 2-(1,4-benzodiazepin-2-ylidene)acetamide Chemical class NC(=O)C=C1C=NC=C2C=CC=CC2=N1 RFRJZWOCMUTXJR-UHFFFAOYSA-N 0.000 description 2
- OBVBSLBPEHFWDI-UHFFFAOYSA-N 2-(7-chloro-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-ylidene)acetamide Chemical compound N=1CC(=CC(N)=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 OBVBSLBPEHFWDI-UHFFFAOYSA-N 0.000 description 2
- NXDXAZVIDNUKSY-UHFFFAOYSA-N 2-[5-(2-chlorophenyl)-1-methyl-7-nitro-3h-1,4-benzodiazepin-2-ylidene]acetamide Chemical compound N=1CC(=CC(N)=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1Cl NXDXAZVIDNUKSY-UHFFFAOYSA-N 0.000 description 2
- OMFDUYQHMRAVBY-UHFFFAOYSA-N 2-[7-bromo-5-(2-chlorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-ylidene]acetamide Chemical compound N=1CC(=CC(N)=O)N(C)C2=CC=C(Br)C=C2C=1C1=CC=CC=C1Cl OMFDUYQHMRAVBY-UHFFFAOYSA-N 0.000 description 2
- UXZLCTPPDQCADI-UHFFFAOYSA-N 2-[7-bromo-5-(2-fluorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-ylidene]acetamide Chemical compound N=1CC(=CC(N)=O)N(C)C2=CC=C(Br)C=C2C=1C1=CC=CC=C1F UXZLCTPPDQCADI-UHFFFAOYSA-N 0.000 description 2
- IGNVKXLGRBJBSK-UHFFFAOYSA-N 2-[7-chloro-5-(2-chlorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-ylidene]acetamide Chemical compound N=1CC(=CC(N)=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl IGNVKXLGRBJBSK-UHFFFAOYSA-N 0.000 description 2
- QUEHUYSSVUPPJT-UHFFFAOYSA-N 2-[7-chloro-5-(2-fluorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-ylidene]acetamide Chemical compound N=1CC(=CC(N)=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F QUEHUYSSVUPPJT-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000002539 anti-aggressive effect Effects 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003874 central nervous system depressant Substances 0.000 description 2
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 2
- 229960004782 chlordiazepoxide Drugs 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 229960002456 hexobarbital Drugs 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000010998 test method Methods 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
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- GXNWIQJCTLCESC-UHFFFAOYSA-N 1-phenyl-2,3-dihydro-1,4-benzodiazepine Chemical class C12=CC=CC=C2C=NCCN1C1=CC=CC=C1 GXNWIQJCTLCESC-UHFFFAOYSA-N 0.000 description 1
- DAASTDFNLASTNS-UHFFFAOYSA-N 2-(1,4-benzodiazepin-2-ylidene)acetonitrile Chemical class N#CC=C1C=NC=C2C=CC=CC2=N1 DAASTDFNLASTNS-UHFFFAOYSA-N 0.000 description 1
- XDGGOGFWSFMUJZ-UHFFFAOYSA-N 2-(7-chloro-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-ylidene)acetonitrile Chemical compound N=1CC(=CC#N)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 XDGGOGFWSFMUJZ-UHFFFAOYSA-N 0.000 description 1
- XUOPICBGRSLIEN-UHFFFAOYSA-N 2-[5-(2-chlorophenyl)-1-methyl-7-nitro-2,3-dihydro-1,4-benzodiazepin-2-yl]acetonitrile Chemical compound C12=CC([N+]([O-])=O)=CC=C2N(C)C(CC#N)CN=C1C1=CC=CC=C1Cl XUOPICBGRSLIEN-UHFFFAOYSA-N 0.000 description 1
- QLWMENOVVOZXLF-UHFFFAOYSA-N 2-[5-(2-chlorophenyl)-1-methyl-7-nitro-3h-1,4-benzodiazepin-2-ylidene]acetonitrile Chemical compound N=1CC(=CC#N)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1Cl QLWMENOVVOZXLF-UHFFFAOYSA-N 0.000 description 1
- DLKPZULPALHXCI-UHFFFAOYSA-N 2-[7-bromo-1-methyl-5-[2-(trifluoromethyl)phenyl]-3h-1,4-benzodiazepin-2-ylidene]acetonitrile Chemical compound N=1CC(=CC#N)N(C)C2=CC=C(Br)C=C2C=1C1=CC=CC=C1C(F)(F)F DLKPZULPALHXCI-UHFFFAOYSA-N 0.000 description 1
- VAWKGAXQSAYYJD-UHFFFAOYSA-N 2-[7-bromo-5-(2-chlorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-ylidene]acetonitrile Chemical compound N=1CC(=CC#N)N(C)C2=CC=C(Br)C=C2C=1C1=CC=CC=C1Cl VAWKGAXQSAYYJD-UHFFFAOYSA-N 0.000 description 1
- MLLBMOQYSZRTQK-UHFFFAOYSA-N 2-[7-bromo-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1,4-benzodiazepin-2-yl]acetonitrile Chemical compound C12=CC(Br)=CC=C2N(C)C(CC#N)CN=C1C1=CC=CC=C1F MLLBMOQYSZRTQK-UHFFFAOYSA-N 0.000 description 1
- AYIHLAQRLWEJAS-UHFFFAOYSA-N 2-[7-bromo-5-(2-fluorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-ylidene]acetonitrile Chemical compound N=1CC(=CC#N)N(C)C2=CC=C(Br)C=C2C=1C1=CC=CC=C1F AYIHLAQRLWEJAS-UHFFFAOYSA-N 0.000 description 1
- IATFPRZSTFLBTN-UHFFFAOYSA-N 2-[7-chloro-1-methyl-5-[2-(trifluoromethyl)phenyl]-3h-1,4-benzodiazepin-2-ylidene]acetonitrile Chemical compound N=1CC(=CC#N)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1C(F)(F)F IATFPRZSTFLBTN-UHFFFAOYSA-N 0.000 description 1
- RZQZSZQCTPNNJI-UHFFFAOYSA-N 2-[7-chloro-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1,4-benzodiazepin-2-yl]acetonitrile Chemical compound C12=CC(Cl)=CC=C2N(C)C(CC#N)CN=C1C1=CC=CC=C1F RZQZSZQCTPNNJI-UHFFFAOYSA-N 0.000 description 1
- VXOUCDPOYYYFAW-UHFFFAOYSA-N 2-[7-chloro-5-(2-fluorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-ylidene]acetonitrile Chemical compound N=1CC(=CC#N)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F VXOUCDPOYYYFAW-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- BUCORZSTKDOEKQ-UHFFFAOYSA-N 7-chloro-4-hydroxy-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-imine Chemical group C=12C=C(Cl)C=CC2=NC(=NC)CN(O)C=1C1=CC=CC=C1 BUCORZSTKDOEKQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010001488 Aggression Diseases 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- RFMOBUSBWVJNHB-UHFFFAOYSA-N Cl.C12=CC(Cl)=CC=C2N(C)C(CNC(C)=O)CN=C1C1=CC=CC=C1 Chemical compound Cl.C12=CC(Cl)=CC=C2N(C)C(CNC(C)=O)CN=C1C1=CC=CC=C1 RFMOBUSBWVJNHB-UHFFFAOYSA-N 0.000 description 1
- 206010053398 Clonic convulsion Diseases 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
- 238000011785 NMRI mouse Methods 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 206010043994 Tonic convulsion Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 208000012761 aggressive behavior Diseases 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- UOCJDOLVGGIYIQ-PBFPGSCMSA-N cefatrizine Chemical group S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)[C@H](N)C=2C=CC(O)=CC=2)CC=1CSC=1C=NNN=1 UOCJDOLVGGIYIQ-PBFPGSCMSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 150000001845 chromium compounds Chemical class 0.000 description 1
- 230000002566 clonic effect Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- XTLNYNMNUCLWEZ-UHFFFAOYSA-N ethanol;propan-2-one Chemical compound CCO.CC(C)=O XTLNYNMNUCLWEZ-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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000012768 molten material Substances 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000004540 pour-on Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 230000001256 tonic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Psychiatry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772754112 DE2754112A1 (de) | 1977-12-05 | 1977-12-05 | 1,4-benzodiazepinderivate, ihre salze und diese verbindungen enthaltende arzneipraeparate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5484586A JPS5484586A (en) | 1979-07-05 |
| JPS6310698B2 true JPS6310698B2 (US20110158925A1-20110630-C00042.png) | 1988-03-08 |
Family
ID=6025339
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14731678A Granted JPS5484586A (en) | 1977-12-05 | 1978-11-30 | 1*44benzodiazepin derivatives*their manufacture and medical drug active to center control*antispasm*muscle relaxation*anxiety mollification and tranquilization |
Country Status (6)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4368157A (en) * | 1978-05-15 | 1983-01-11 | Hoffmann-La Roche Inc. | Intermediates to produce imidazodiazepines |
| US4368158A (en) * | 1978-05-15 | 1983-01-11 | Hoffmann-La Roche Inc. | Intermediates to produce imidazodiazepines |
| US4371468A (en) * | 1978-05-15 | 1983-02-01 | Hoffmann-La Roche Inc. | Intermediates to produce imidazodiazepines |
| US4368159A (en) * | 1978-05-15 | 1983-01-11 | Hoffmann-La Roche Inc. | Intermediates to produce imidazodiazepines |
| US4390471A (en) * | 1978-05-15 | 1983-06-28 | Hoffmann-La Roche Inc. | Imidazodiazepines and processes therefor |
| US4256637A (en) * | 1979-12-20 | 1981-03-17 | Hoffmann-La Roche Inc. | Intermediates for the production of imidazobenzodiazepines |
| US4335042A (en) * | 1980-04-21 | 1982-06-15 | Hoffmann-La Roche Inc. | Process to produce imidazobenzodiazepine intermediates |
| US4752448A (en) * | 1985-12-18 | 1988-06-21 | Keystone Diagnostics, Inc. | Drug abuse test paper |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4941389A (US20110158925A1-20110630-C00042.png) * | 1972-05-03 | 1974-04-18 | ||
| DE2353187A1 (de) * | 1973-05-02 | 1974-11-14 | Kali Chemie Ag | Neue benzodiazepinderivate |
| GB1517164A (en) * | 1974-08-20 | 1978-07-12 | Roche Products Ltd | Substituted-phenyl ketones and a process for the manufacture thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2221536A1 (de) * | 1972-05-03 | 1973-11-22 | Kali Chemie Ag | Verfahren zur herstellung von benzodiazepin-2-on-derivaten |
| DE2358187A1 (de) * | 1973-11-22 | 1975-05-28 | Ernst Schweppe | Vorrichtung an oelbrennern, insbesondere fuer warmwasserheizungen |
| US3998209A (en) * | 1975-12-16 | 1976-12-21 | Macvaugh Gilbert S | Snoring deconditioning system and method |
| US4125726A (en) * | 1977-03-11 | 1978-11-14 | Hoffmann-La Roche Inc. | Imidazo[1,5-a][1,4]benzodiazepines |
-
1977
- 1977-12-05 DE DE19772754112 patent/DE2754112A1/de not_active Withdrawn
-
1978
- 1978-11-16 ES ES475131A patent/ES475131A1/es not_active Expired
- 1978-11-30 JP JP14731678A patent/JPS5484586A/ja active Granted
- 1978-12-01 HU HU78KA1512A patent/HU179210B/hu unknown
- 1978-12-05 US US05/996,720 patent/US4170649A/en not_active Expired - Lifetime
- 1978-12-05 EP EP78101586A patent/EP0024272B1/de not_active Expired
- 1978-12-05 DE DE7878101586T patent/DE2862122D1/de not_active Expired
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4941389A (US20110158925A1-20110630-C00042.png) * | 1972-05-03 | 1974-04-18 | ||
| DE2353187A1 (de) * | 1973-05-02 | 1974-11-14 | Kali Chemie Ag | Neue benzodiazepinderivate |
| GB1517164A (en) * | 1974-08-20 | 1978-07-12 | Roche Products Ltd | Substituted-phenyl ketones and a process for the manufacture thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| HU179210B (en) | 1982-09-28 |
| EP0024272B1 (de) | 1982-12-08 |
| DE2862122D1 (en) | 1983-01-13 |
| JPS5484586A (en) | 1979-07-05 |
| EP0024272A1 (de) | 1981-03-04 |
| ES475131A1 (es) | 1979-04-01 |
| DE2754112A1 (de) | 1979-06-13 |
| US4170649A (en) | 1979-10-09 |
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