IL33859A - S-triazolo(4,3-a)(1,4)-benzodiazepines - Google Patents
S-triazolo(4,3-a)(1,4)-benzodiazepinesInfo
- Publication number
- IL33859A IL33859A IL33859A IL3385970A IL33859A IL 33859 A IL33859 A IL 33859A IL 33859 A IL33859 A IL 33859A IL 3385970 A IL3385970 A IL 3385970A IL 33859 A IL33859 A IL 33859A
- Authority
- IL
- Israel
- Prior art keywords
- benzodiazepine
- phenyl
- chloro
- compound
- triazolo
- Prior art date
Links
- LGNWUMGEJQAWQD-UHFFFAOYSA-N 1h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical class N1=CC2=CC=CC=C2N2CN=NC2=C1 LGNWUMGEJQAWQD-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 54
- -1 inclusive Chemical group 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- 229940049706 benzodiazepine Drugs 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 14
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 13
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical group C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 150000002431 hydrogen Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- WJCUWDGSQTYGRF-UHFFFAOYSA-N 8-chloro-6-(2,6-difluorophenyl)-1-methyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=C(F)C=CC=C1F WJCUWDGSQTYGRF-UHFFFAOYSA-N 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 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 claims description 3
- WKKPJAZBRIGNMG-UHFFFAOYSA-N ethyl 8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-1-carboxylate Chemical compound C12=CC(Cl)=CC=C2N2C(C(=O)OCC)=NN=C2CN=C1C1=CC=CC=C1 WKKPJAZBRIGNMG-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- RKQFBOPLNMCUMU-UHFFFAOYSA-N 1-methyl-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 RKQFBOPLNMCUMU-UHFFFAOYSA-N 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 2
- QXKHYNVANLEOEG-UHFFFAOYSA-N Methoxsalen Chemical group C1=CC(=O)OC2=C1C=C1C=COC1=C2OC QXKHYNVANLEOEG-UHFFFAOYSA-N 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- WSDQIHATCCOMLH-UHFFFAOYSA-N phenyl n-(3,5-dichlorophenyl)carbamate Chemical compound ClC1=CC(Cl)=CC(NC(=O)OC=2C=CC=CC=2)=C1 WSDQIHATCCOMLH-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 104
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 230000008018 melting Effects 0.000 description 40
- 238000002844 melting Methods 0.000 description 40
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 239000000047 product Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 21
- 229910052757 nitrogen Inorganic materials 0.000 description 19
- 241000699670 Mus sp. Species 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 14
- GSIGZZKHXAAYOA-UHFFFAOYSA-N 6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC=CC=C2N2C=NN=C2CN=C1C1=CC=CC=C1 GSIGZZKHXAAYOA-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000002211 ultraviolet spectrum Methods 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 230000005587 bubbling Effects 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000000538 analytical sample Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- ROFVGYAMRSGUSQ-UHFFFAOYSA-N 1-(2-bromoethyl)piperazine;hydrobromide Chemical compound Br.BrCCN1CCNCC1 ROFVGYAMRSGUSQ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000012258 stirred mixture Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FPTCVTJCJMVIDV-UHFFFAOYSA-N 2-phenylacetohydrazide Chemical compound NNC(=O)CC1=CC=CC=C1 FPTCVTJCJMVIDV-UHFFFAOYSA-N 0.000 description 3
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 3
- WENMWXYJTWETRE-UHFFFAOYSA-N 7-chloro-5-(2,6-difluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound FC1=CC=CC(F)=C1C1=NCC(=O)NC2=CC=C(Cl)C=C12 WENMWXYJTWETRE-UHFFFAOYSA-N 0.000 description 3
- MPZVLJCMGPYWQQ-UHFFFAOYSA-N 8-chloro-6-(2-fluorophenyl)-1-methyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1F MPZVLJCMGPYWQQ-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000008485 antagonism Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 150000001557 benzodiazepines Chemical class 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- FLGJKAWEVKYTSD-UHFFFAOYSA-N methyl 2-amino-5-(1-phenylethyl)thiophene-3-carboxylate Chemical compound S1C(N)=C(C(=O)OC)C=C1C(C)C1=CC=CC=C1 FLGJKAWEVKYTSD-UHFFFAOYSA-N 0.000 description 3
- 239000003158 myorelaxant agent Substances 0.000 description 3
- PNVDZEPMVZSZKT-UHFFFAOYSA-N n-[4-chloro-2-(2,6-difluorobenzoyl)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(Cl)C=C1C(=O)C1=C(F)C=CC=C1F PNVDZEPMVZSZKT-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 230000002936 tranquilizing effect Effects 0.000 description 3
- JOFWLTCLBGQGBO-UHFFFAOYSA-N triazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl JOFWLTCLBGQGBO-UHFFFAOYSA-N 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- DUMGVPIXKALANS-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-(2,6-difluorophenyl)methanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=C(F)C=CC=C1F DUMGVPIXKALANS-UHFFFAOYSA-N 0.000 description 2
- GOOCRIHPADOQAS-ZNUXJMJHSA-N (4ar,5as,8ar,13as,15as,15br)-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2h-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinoline-14-one;sulfuric acid Chemical compound OS(O)(=O)=O.O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1.O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 GOOCRIHPADOQAS-ZNUXJMJHSA-N 0.000 description 2
- ZLRDSGHNBCXCBE-UHFFFAOYSA-N 1-ethyl-8-methyl-6-phenyl-10-propylsulfonyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound CCCS(=O)(=O)C1=CC(C)=CC2=C1N1C(CC)=NN=C1CN=C2C1=CC=CC=C1 ZLRDSGHNBCXCBE-UHFFFAOYSA-N 0.000 description 2
- BTYFPUAHZUNPRP-UHFFFAOYSA-N 1-methyl-6-phenyl-8-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(C(F)(F)F)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 BTYFPUAHZUNPRP-UHFFFAOYSA-N 0.000 description 2
- KJCILEUWXWKFQI-UHFFFAOYSA-N 2-(1-methyl-7-nitro-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-6-yl)benzonitrile Chemical compound C1=CC=C([N+]([O-])=O)C2=C1N1C(C)=NN=C1CN=C2C1=CC=CC=C1C#N KJCILEUWXWKFQI-UHFFFAOYSA-N 0.000 description 2
- NKPQZVBLZKRXLD-UHFFFAOYSA-N 2-bromo-n-[4-chloro-2-(2,6-difluorobenzoyl)phenyl]acetamide Chemical compound FC1=CC=CC(F)=C1C(=O)C1=CC(Cl)=CC=C1NC(=O)CBr NKPQZVBLZKRXLD-UHFFFAOYSA-N 0.000 description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- VBLQRGCEOICABD-UHFFFAOYSA-N 6-(2-bromophenyl)-1-ethyl-7-ethylsulfanyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound CCSC1=CC=CC(N2C(CC)=NN=C2CN=2)=C1C=2C1=CC=CC=C1Br VBLQRGCEOICABD-UHFFFAOYSA-N 0.000 description 2
- DJGPBHIGXLAPNI-UHFFFAOYSA-N 6-(2-chlorophenyl)-1,4,7,9-tetramethyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=C(C)C=C(C)C=C2N2C(C)=NN=C2C(C)N=C1C1=CC=CC=C1Cl DJGPBHIGXLAPNI-UHFFFAOYSA-N 0.000 description 2
- CXDBEERFLVJERN-UHFFFAOYSA-N 6-(2-chlorophenyl)-9-nitro-1-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C([N+](=O)[O-])=CC=C2C=1N(C(=NN=1)C=3C=CC=CC=3)C=1CN=C2C1=CC=CC=C1Cl CXDBEERFLVJERN-UHFFFAOYSA-N 0.000 description 2
- IPDRIVUICIZFOU-UHFFFAOYSA-N 6-(2-nitrophenyl)-n,n-dipropyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-8-amine Chemical compound C=1C(N(CCC)CCC)=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=CC=C1[N+]([O-])=O IPDRIVUICIZFOU-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- ZEOODRPZUKFNCC-UHFFFAOYSA-N 8-bromo-6-(2-fluorophenyl)-4-methyl-1-propan-2-yl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(Br)=CC=C2N2C(C(C)C)=NN=C2C(C)N=C1C1=CC=CC=C1F ZEOODRPZUKFNCC-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
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- FCCCRBDJBTVFSJ-UHFFFAOYSA-N butanehydrazide Chemical compound CCCC(=O)NN FCCCRBDJBTVFSJ-UHFFFAOYSA-N 0.000 description 2
- SEFWTSGILSSUGC-UHFFFAOYSA-N butyl 8-chloro-6-(3-nitrophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-1-carboxylate Chemical compound C12=CC(Cl)=CC=C2N2C(C(=O)OCCCC)=NN=C2CN=C1C1=CC=CC([N+]([O-])=O)=C1 SEFWTSGILSSUGC-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- CGPJOSVQEHYXRV-UHFFFAOYSA-N methyl 6-(2,4-dichlorophenyl)-9-fluoro-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-1-carboxylate Chemical compound C12=CC=C(F)C=C2N2C(C(=O)OC)=NN=C2CN=C1C1=CC=C(Cl)C=C1Cl CGPJOSVQEHYXRV-UHFFFAOYSA-N 0.000 description 2
- GUWXLNHWNBLWMV-UHFFFAOYSA-N n,n-dimethyl-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-8-amine Chemical compound C=1C(N(C)C)=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=CC=C1 GUWXLNHWNBLWMV-UHFFFAOYSA-N 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
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- 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
- 150000002632 lipids Chemical class 0.000 description 1
- 230000002101 lytic effect Effects 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
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- RIYMFZCORTVORQ-UHFFFAOYSA-N n'-(7-chloro-5-phenyl-3h-1,4-benzodiazepin-2-yl)acetohydrazide Chemical compound N=1CC(NNC(=O)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 RIYMFZCORTVORQ-UHFFFAOYSA-N 0.000 description 1
- QYXCLLKWKKQHJZ-UHFFFAOYSA-N n-[1-propyl-6-(3-propylsulfanylphenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-9-yl]propanamide Chemical compound CCCSC1=CC=CC(C=2C3=CC=C(NC(=O)CC)C=C3N3C(CCC)=NN=C3CN=2)=C1 QYXCLLKWKKQHJZ-UHFFFAOYSA-N 0.000 description 1
- OQACDFCYZHWJEN-UHFFFAOYSA-N n-[4-[10-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-6-yl]phenyl]propanamide Chemical compound C1=CC(NC(=O)CC)=CC=C1C1=NCC2=NN=CN2C2=C1C=CC=C2C(F)(F)F OQACDFCYZHWJEN-UHFFFAOYSA-N 0.000 description 1
- VVSHFQJBRBGKEA-UHFFFAOYSA-N n-[4-[2-sulfanylidene-9-(trifluoromethyl)-1,3-dihydro-1,4-benzodiazepin-5-yl]phenyl]propanamide Chemical compound C1=CC(NC(=O)CC)=CC=C1C1=NCC(=S)NC2=C1C=CC=C2C(F)(F)F VVSHFQJBRBGKEA-UHFFFAOYSA-N 0.000 description 1
- XQPKCYIBOZQAIK-UHFFFAOYSA-N n-[4-[9-(dipropylamino)-1-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-6-yl]phenyl]propanamide Chemical compound C=1C(N(CCC)CCC)=CC=C2C=1N(C(=NN=1)C=3C=CC=CC=3)C=1CN=C2C1=CC=C(NC(=O)CC)C=C1 XQPKCYIBOZQAIK-UHFFFAOYSA-N 0.000 description 1
- CGIOEFBVEXUSEM-UHFFFAOYSA-N n-[6-(4-cyanophenyl)-1-ethyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-10-yl]acetamide Chemical compound C12=CC=CC(NC(C)=O)=C2N2C(CC)=NN=C2CN=C1C1=CC=C(C#N)C=C1 CGIOEFBVEXUSEM-UHFFFAOYSA-N 0.000 description 1
- CVTJVXBIKXMWRQ-UHFFFAOYSA-N n-[6-(4-iodophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-8-yl]acetamide Chemical compound C=1C(NC(=O)C)=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=C(I)C=C1 CVTJVXBIKXMWRQ-UHFFFAOYSA-N 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
- 150000007524 organic acids Chemical class 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
- 239000012071 phase 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
- 239000002244 precipitate Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000010561 standard procedure Methods 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
- 229960005453 strychnine Drugs 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229940125725 tranquilizer 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
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
-
- 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
- C07D243/20—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Fodder In General (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL38810A IL38810A0 (en) | 1970-02-09 | 1972-02-22 | Novel benzodiazepines and their production |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80793369A | 1969-03-17 | 1969-03-17 | |
| US04/872,394 US3987052A (en) | 1969-03-17 | 1969-10-29 | 6-Phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL33859A0 IL33859A0 (en) | 1970-04-20 |
| IL33859A true IL33859A (en) | 1973-01-30 |
Family
ID=27123060
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL33859A IL33859A (en) | 1969-03-17 | 1970-02-09 | S-triazolo(4,3-a)(1,4)-benzodiazepines |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US3987052A (pl) |
| JP (1) | JPS4940239B1 (pl) |
| AU (2) | AU491139B2 (pl) |
| BE (1) | BE747493A (pl) |
| BR (1) | BR7017488D0 (pl) |
| CH (1) | CH535788A (pl) |
| DE (1) | DE2012190C3 (pl) |
| ES (1) | ES376689A1 (pl) |
| FR (1) | FR2034999A1 (pl) |
| GB (1) | GB1291631A (pl) |
| HK (1) | HK61677A (pl) |
| IL (1) | IL33859A (pl) |
| NL (2) | NL172510C (pl) |
| OA (1) | OA03446A (pl) |
| PH (1) | PH9329A (pl) |
| PL (1) | PL80541B1 (pl) |
| SE (1) | SE387641B (pl) |
| YU (1) | YU35139B (pl) |
Families Citing this family (82)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE779988R (fr) * | 1969-03-17 | 1972-08-29 | Upjohn Co | Nouvelles 6-phenyl-4h-s-triazolo(4,3-a)(1,4)- benzodiazepines douees d'activite pharmacologique et leur procede de |
| BE758921A (fr) * | 1969-11-15 | 1971-04-16 | Takeda Chemical Industries Ltd | Derives de benzodiazepine |
| BE759099A (fr) * | 1969-11-18 | 1971-04-30 | Takeda Chemical Industries Ltd | Procede de fabrication de composes heterocycliques |
| YU34997B (en) * | 1970-03-27 | 1980-06-30 | Hiroyuki Tawada | Process for preparing benzodiazepine derivatives |
| DE2156472A1 (de) * | 1970-11-23 | 1972-05-31 | Ciba-Geigy Ag, Basel (Schweiz) | Verfahren zur Herstellung von neuen Diazepinderivaten |
| CH544764A (de) * | 1971-01-21 | 1974-01-15 | Ciba Geigy Ag | Verfahren zur Herstellung von neuen Triazolo-benzodiazepinderivaten |
| US3709898A (en) * | 1971-02-09 | 1973-01-09 | Upjohn Co | Process for the production of triazolobenzodiazepines and intermediates |
| DE2164778C2 (de) * | 1971-03-03 | 1984-07-05 | The Upjohn Co., Kalamazoo, Mich. | 6-(o-Chlorphenyl)-1-methyl-4H-s-triazolo[4,3-a][1,4]-benzodiazepin und dieses enthaltende pharmazeutische Präparat |
| DE2164777A1 (de) * | 1971-03-03 | 1972-09-07 | Upjohn Co | 8-Nitro-6-(o-halogenphenyl)-l-methyl-4H-s-triazolo eckige Klammer auf 4,3-a eckige Klammer zu-eckige Klammer auf 1-4 eckige Klammer zu benzodiazepine und diese enthaltende pharmazeutische Präparate |
| YU36376B (en) * | 1971-03-03 | 1983-06-30 | Upjohn Co | Process for producing dihalo-6-phenyltriazolobenzodiazepine-5-n-oxide |
| CH545302A (de) * | 1971-04-08 | 1974-01-13 | Ciba Geigy Ag | Verfahren zur Herstellung von neuen Triazolo-benzodiazepinderivaten |
| US3759943A (en) * | 1971-04-28 | 1973-09-18 | Upjohn Co | Amido and amino triazolo benzodiazepines |
| GB1331015A (en) * | 1971-04-28 | 1973-09-19 | Upjohn Co | 1-substituted-6-phenyl-4h-s-triazolo-4,3-a-1,4-benzodiazepines |
| GB1323277A (en) * | 1971-05-10 | 1973-07-11 | Upjohn Co | Triazolobenzodiazepines |
| US3734922A (en) * | 1971-05-11 | 1973-05-22 | Upjohn Co | Certain 4h-s-triazolo(4,3-a)(1,4)benzodiazepines |
| US4000289A (en) * | 1971-07-08 | 1976-12-28 | The Upjohn Company | Animal feed and process |
| BE787251A (fr) * | 1971-08-04 | 1973-02-05 | Upjohn Co | Nouvelles benzodiazepines et leur preparation |
| US3870793A (en) * | 1971-08-09 | 1975-03-11 | Upjohn Co | Animal feed and process |
| GB1373300A (en) * | 1971-09-08 | 1974-11-06 | Upjohn Co | Triazolobenzodiazepines and the manufacture thereof |
| US3767661A (en) * | 1971-09-13 | 1973-10-23 | Upjohn Co | 4h-s-triazolo(4,3-a)(1,4)benzodiazepines |
| GB1381158A (en) * | 1971-09-13 | 1975-01-22 | Upjohn Co | Benzodiazepines and the manufacture thereof |
| US3714178A (en) * | 1971-09-30 | 1973-01-30 | Upjohn Co | 6,7-DIHYDRO-7-ALKYL-5H-1,2,4-TRIAZOLO[4,3-d][1,4]BENZODIAZEPINES AND THEIR PRODUCTION |
| BE790838A (fr) * | 1971-11-02 | 1973-04-30 | Upjohn Co | Nouvelles 1-aminophenyl-6-phenyl-s-triazolo (4,3-a) (1,4)- benzodiazepines, leur procede de preparation et medicament les contenant |
| FI53821C (fi) * | 1971-11-15 | 1978-08-10 | Ciba Geigy Ag | Foerfarande foer framstaellning av farmakologiskt vaerdefull 6-fenyl-8-klor-4h-s-triazolo(4 3-a)(1 4)bensodiazepin-1-metanol |
| FR2128552A2 (en) * | 1972-03-02 | 1972-10-20 | Upjohn Co | S-triazolo (4,3-a) (1,4) benzodiazepines - as anxiolytic agents, muscle relaxants |
| CH572056A5 (pl) * | 1972-11-28 | 1976-01-30 | Ciba Geigy Ag | |
| CH579083A5 (pl) * | 1972-12-29 | 1976-08-31 | Ciba Geigy Ag | |
| US4978753A (en) * | 1973-01-15 | 1990-12-18 | The Upjohn Company | 7-phenylpyrimido[1,2-alpha][1,4]benzodiazepin-3(5H)-ones |
| US4082761A (en) * | 1973-09-04 | 1978-04-04 | The Upjohn Company | Triazolo[4,3-a][1,4]benzodiazepinium quaternary salts |
| US4169150A (en) * | 1975-11-12 | 1979-09-25 | Teijin Limited | Benzodiazepine derivatives and pharmaceutical compositions containing said derivatives |
| US4431589A (en) * | 1980-12-11 | 1984-02-14 | Lilly House | Benzodiazepine compounds and their use as pharmaceuticals |
| US4455307A (en) * | 1982-01-04 | 1984-06-19 | The Upjohn Company | Antihypertensive use of triazolobenzodiazepines |
| US4375473A (en) * | 1982-01-04 | 1983-03-01 | The Upjohn Company | Method |
| DE3332830A1 (de) * | 1982-09-16 | 1984-03-22 | The Upjohn Co., 49001 Kalamazoo, Mich. | Verwendung von benzodiazepinen zur bekaempfung oder bei der behandlung von panikzustaenden |
| US4481208A (en) * | 1983-06-06 | 1984-11-06 | The Upjohn Company | Treatment of panic disorders with estazolam |
| US4508726A (en) * | 1982-09-16 | 1985-04-02 | The Upjohn Company | Treatment of panic disorders with alprazolam |
| US4514407A (en) * | 1983-03-17 | 1985-04-30 | The Upjohn Company | 1-Ethanamine-triazolo-benzodiazepines as diuretics |
| US4689413A (en) * | 1983-03-17 | 1987-08-25 | The Upjohn Company | Triazolo-benzodiazepine-1-ethanamines as diuretics |
| US4474699A (en) * | 1983-05-25 | 1984-10-02 | The Upjohn Company | Preparing 1-aminomethyl-6-substituted-4H-s-triazolo[4,3-a][1,4]benzodiazepines in improved procedures |
| US4588721A (en) * | 1983-09-12 | 1986-05-13 | The Upjohn Company | Treatment of negative symptoms of schizophrenia |
| US4547499A (en) * | 1984-05-10 | 1985-10-15 | The Upjohn Company | 2,4-Dihydro-2(omega-aminoalkyl)-1H-[1,2,4]triazolo[3,4-c]benzoxazin-1-one anti-allergy drug compounds, compositions and use |
| US4634703A (en) * | 1985-10-25 | 1987-01-06 | Bristol-Myers Company | Method for alleviation of panic disorders |
| US4959361A (en) * | 1987-12-18 | 1990-09-25 | Hoffmann-La Roche Inc. | Triazolo(4,3-A)(1,4)benzodiazepines and thieno (3,2-F)(1,2,4)triazolo(4,3-A)(1,4)diazepine compounds which have useful activity as platelet activating factor (PAF) antagonists |
| US5334592A (en) * | 1988-04-27 | 1994-08-02 | Schering Corporation | Certain PAF antagonist antihistamine combinations and methods |
| US4856303A (en) * | 1988-07-21 | 1989-08-15 | Whirlpool Corporation | Agitator thrust spacer for automatic washer |
| US5225198A (en) * | 1991-08-27 | 1993-07-06 | Cygnus Therapeutic Systems | Transdermal administration of short or intermediate half-life benzodiazepines |
| US5900250A (en) * | 1992-05-13 | 1999-05-04 | Alza Corporation | Monoglyceride/lactate ester permeation enhancer for oxybutnin |
| JP3688293B2 (ja) * | 1993-09-29 | 2005-08-24 | アルザ・コーポレーション | モノグリセリド／乳酸エステル透過促進剤 |
| ATE247967T1 (de) | 1998-06-09 | 2003-09-15 | Takeda Chemical Industries Ltd | Pharmazeutische kombination mit einem trizyclischen komponent und mindestens einem aus zolpidem, zopiclone und brotizolam, zur behandlung von schlafstörungen |
| US6737042B2 (en) * | 2001-05-24 | 2004-05-18 | Alexza Molecular Delivery Corporation | Delivery of drug esters through an inhalation route |
| US7585493B2 (en) | 2001-05-24 | 2009-09-08 | Alexza Pharmaceuticals, Inc. | Thin-film drug delivery article and method of use |
| US20070122353A1 (en) | 2001-05-24 | 2007-05-31 | Hale Ron L | Drug condensation aerosols and kits |
| US7090830B2 (en) | 2001-05-24 | 2006-08-15 | Alexza Pharmaceuticals, Inc. | Drug condensation aerosols and kits |
| US7645442B2 (en) | 2001-05-24 | 2010-01-12 | Alexza Pharmaceuticals, Inc. | Rapid-heating drug delivery article and method of use |
| US7766013B2 (en) | 2001-06-05 | 2010-08-03 | Alexza Pharmaceuticals, Inc. | Aerosol generating method and device |
| US7458374B2 (en) | 2002-05-13 | 2008-12-02 | Alexza Pharmaceuticals, Inc. | Method and apparatus for vaporizing a compound |
| US20040105818A1 (en) | 2002-11-26 | 2004-06-03 | Alexza Molecular Delivery Corporation | Diuretic aerosols and methods of making and using them |
| US7913688B2 (en) | 2002-11-27 | 2011-03-29 | Alexza Pharmaceuticals, Inc. | Inhalation device for producing a drug aerosol |
| US20050079166A1 (en) | 2003-05-21 | 2005-04-14 | Alexza Molecular Delivery Corporation | Self-contained heating unit and drug-supply unit employing same |
| EP1667663A1 (en) * | 2003-09-26 | 2006-06-14 | Alza Corporation, c/o Johnson & Johnson | Osmotic dosage forms for controlled delivery of alprazolam |
| US20050163843A1 (en) * | 2003-12-31 | 2005-07-28 | Garth Boehm | Alprazolam formulations |
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| CA2576961A1 (en) | 2004-08-12 | 2006-03-02 | Alexza Pharmaceuticals, Inc. | Aerosol drug delivery device incorporating percussively activated heat packages |
| US8277840B2 (en) * | 2005-07-22 | 2012-10-02 | Emcure Pharmaceuticals Limited | Sustained release formulation of alprazolam |
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| US20070218135A1 (en) * | 2006-03-14 | 2007-09-20 | Glenmark Pharmaceuticals Limited | Sustained release matrix pharmaceutical composition |
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| US8106189B2 (en) * | 2007-10-03 | 2012-01-31 | Centaur Chemicals Pvt Ltd | Process for preparation of triazol-benzodiazepine derivatives |
| ES2403193T3 (es) | 2008-02-05 | 2013-05-16 | Laboratorios Bago S.A. | Composiciones que comprenden alprazolam para el tratamiento del insomnio primario y del insomnio asociado con estados de ansiedad y procedimientos para su preparación |
| EP2271347B1 (en) | 2008-03-28 | 2016-05-11 | Hale Biopharma Ventures, Llc | Administration of benzodiazepine compositions |
| US10289671B2 (en) * | 2008-05-07 | 2019-05-14 | Microsoft Technology Licensing, Llc | Graphically displaying selected data sources within a grid |
| WO2010074753A1 (en) | 2008-12-23 | 2010-07-01 | Map Pharmaceuticals, Inc. | Inhalation devices and related methods for administration of sedative hypnotic compounds |
| EP3415139B8 (en) | 2011-06-14 | 2022-05-18 | Neurelis, Inc. | Administration of benzodiazepine |
| CN109906220A (zh) | 2016-11-01 | 2019-06-18 | 豪夫迈·罗氏有限公司 | 用于治疗cns相关疾病的1,3-二氢-1,4-苯并二氮杂*-2-硫酮化合物 |
| HUE064864T2 (hu) | 2016-12-09 | 2024-04-28 | Alexza Pharmaceuticals Inc | Az alprazolam alkalmazása epilepszia kezelésében |
| KR102852740B1 (ko) | 2018-02-02 | 2025-08-29 | 알렉스자 파마스티칼즈, 인크. | 전기적 응축 에어로졸 디바이스 |
| CN109748922B (zh) * | 2019-01-15 | 2020-04-14 | 山东安信制药有限公司 | 一种阿普唑仑i晶型的制备方法 |
| CN115380034A (zh) * | 2020-03-31 | 2022-11-22 | 豪夫迈·罗氏有限公司 | 作为GABA Aγ1 PAM的苯并二氮杂䓬衍生物 |
| EP3901155A1 (en) * | 2020-04-20 | 2021-10-27 | F. Hoffmann-La Roche AG | New benzodiazepine derivatives as gaba a gamma1 pam |
| WO2023052312A1 (en) | 2021-09-29 | 2023-04-06 | F. Hoffmann-La Roche Ag | New benzodiazepine derivatives as gaba a gamma1 pam |
| WO2023057415A1 (en) | 2021-10-06 | 2023-04-13 | F. Hoffmann-La Roche Ag | Benzodiazepine derivatives as positive allosteric modulators of the gaba a gamma1 receptor |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2891862A (en) * | 1956-11-06 | 1959-06-23 | Eastman Kodak Co | Stabilized photographic silver halide emulsions |
| NL126389C (pl) * | 1962-07-10 | |||
| US3523947A (en) * | 1966-11-23 | 1970-08-11 | Hoffmann La Roche | 1-cyclic amidine-5-aryl-1,4-benzodiazepine and process |
-
1969
- 1969-10-29 US US04/872,394 patent/US3987052A/en not_active Expired - Lifetime
-
1970
- 1970-02-05 GB GB5532/70A patent/GB1291631A/en not_active Expired
- 1970-02-09 IL IL33859A patent/IL33859A/en unknown
- 1970-02-12 YU YU345/70A patent/YU35139B/xx unknown
- 1970-02-18 ES ES376689A patent/ES376689A1/es not_active Expired
- 1970-02-26 SE SE7002516A patent/SE387641B/xx unknown
- 1970-02-27 PH PH11194*UA patent/PH9329A/en unknown
- 1970-03-13 JP JP45020940A patent/JPS4940239B1/ja active Pending
- 1970-03-14 DE DE2012190A patent/DE2012190C3/de not_active Expired
- 1970-03-16 FR FR7009329A patent/FR2034999A1/fr active Granted
- 1970-03-16 BR BR217488/70A patent/BR7017488D0/pt unknown
- 1970-03-16 PL PL1970139414A patent/PL80541B1/pl unknown
- 1970-03-16 CH CH391770A patent/CH535788A/de not_active IP Right Cessation
- 1970-03-16 OA OA53877A patent/OA03446A/fr unknown
- 1970-03-17 NL NLAANVRAGE7003750,A patent/NL172510C/xx not_active IP Right Cessation
- 1970-03-17 BE BE747493A patent/BE747493A/fr not_active IP Right Cessation
-
1975
- 1975-10-07 AU AU85499/75A patent/AU491139B2/en not_active Expired
- 1975-10-07 AU AU85500/75A patent/AU490626B2/en not_active Expired
-
1977
- 1977-12-15 HK HK616/77A patent/HK61677A/xx unknown
-
1981
- 1981-01-09 NL NLAANVRAGE8100081,A patent/NL170857C/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE387641B (sv) | 1976-09-13 |
| NL170857B (nl) | 1982-08-02 |
| FR2034999A1 (fr) | 1970-12-18 |
| NL7003750A (nl) | 1970-09-21 |
| NL8100081A (nl) | 1981-04-29 |
| OA03446A (fr) | 1971-03-30 |
| NL170857C (nl) | 1983-01-03 |
| IL33859A0 (en) | 1970-04-20 |
| JPS4940239B1 (pl) | 1974-10-31 |
| BR7017488D0 (pt) | 1973-02-13 |
| PH9329A (en) | 1975-09-23 |
| HK61677A (en) | 1977-12-23 |
| NL172510B (nl) | 1983-04-18 |
| BE747493A (fr) | 1970-09-17 |
| CH535788A (de) | 1973-04-15 |
| GB1291631A (en) | 1972-10-04 |
| DE2012190C3 (de) | 1980-11-13 |
| AU490626B2 (en) | 1975-12-18 |
| YU34570A (en) | 1979-04-30 |
| US3987052A (en) | 1976-10-19 |
| FR2034999B1 (pl) | 1973-07-13 |
| DE2012190A1 (de) | 1970-09-24 |
| AU8549975A (en) | 1975-12-18 |
| YU35139B (en) | 1980-09-25 |
| NL172510C (nl) | 1983-09-16 |
| AU8550075A (en) | 1975-12-18 |
| PL80541B1 (pl) | 1975-08-30 |
| AU491139B2 (en) | 1975-12-18 |
| ES376689A1 (es) | 1972-05-01 |
| DE2012190B2 (de) | 1980-03-06 |
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