NO762525L - - Google Patents
Info
- Publication number
- NO762525L NO762525L NO762525A NO762525A NO762525L NO 762525 L NO762525 L NO 762525L NO 762525 A NO762525 A NO 762525A NO 762525 A NO762525 A NO 762525A NO 762525 L NO762525 L NO 762525L
- Authority
- NO
- Norway
- Prior art keywords
- benzodiazepine
- ppm
- dihydro
- fluoro
- formula
- Prior art date
Links
- 239000000460 chlorine Substances 0.000 claims description 31
- 150000001875 compounds Chemical class 0.000 claims description 28
- 229910052801 chlorine Inorganic materials 0.000 claims description 26
- 229910052794 bromium Inorganic materials 0.000 claims description 23
- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- 239000011737 fluorine Substances 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- 239000007858 starting material Substances 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000002168 alkylating agent Substances 0.000 claims description 6
- 229940100198 alkylating agent Drugs 0.000 claims description 6
- 150000002431 hydrogen Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- LJEAWFCRPWEPNO-UHFFFAOYSA-N 7-bromo-3-fluoro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Br)=CC=C2NC(=O)C(F)N=C1C1=CC=CC=C1 LJEAWFCRPWEPNO-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- NINGMRSNYNFRCB-UHFFFAOYSA-N 7-chloro-3-fluoro-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1C(F)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 NINGMRSNYNFRCB-UHFFFAOYSA-N 0.000 claims description 3
- PKSRYZZPYBHMKE-UHFFFAOYSA-N 7-chloro-3-fluoro-5-(2-fluorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1C(F)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F PKSRYZZPYBHMKE-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 3
- JJACTJCMCKSYQL-UHFFFAOYSA-N 7-bromo-3-fluoro-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1C(F)C(=O)N(C)C2=CC=C(Br)C=C2C=1C1=CC=CC=C1 JJACTJCMCKSYQL-UHFFFAOYSA-N 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 3
- 239000012022 methylating agents Substances 0.000 claims 3
- 239000001301 oxygen Substances 0.000 claims 3
- 229910052760 oxygen Inorganic materials 0.000 claims 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 22
- 238000012360 testing method Methods 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 14
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 239000005457 ice water Substances 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- 229910052736 halogen Inorganic materials 0.000 description 9
- -1 inorganic acid halide Chemical class 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 229940049706 benzodiazepine Drugs 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- 230000011514 reflex Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 150000001557 benzodiazepines Chemical class 0.000 description 7
- 239000003158 myorelaxant agent Substances 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 6
- 230000035939 shock Effects 0.000 description 6
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 230000001629 suppression Effects 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 5
- 229940029284 trichlorofluoromethane Drugs 0.000 description 5
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000000932 sedative agent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- PZOZHMBWLDUJCP-UHFFFAOYSA-N 3-fluoro-1H-1,2-benzodiazepine Chemical class FC1=NNC2=C(C=C1)C=CC=C2 PZOZHMBWLDUJCP-UHFFFAOYSA-N 0.000 description 3
- LAAYFWALJDHMAB-UHFFFAOYSA-N 7-bromo-5-(2-fluorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Br)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1F LAAYFWALJDHMAB-UHFFFAOYSA-N 0.000 description 3
- IEAZSLKYQNZPRN-UHFFFAOYSA-N 7-chloro-3-fluoro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(F)N=C1C1=CC=CC=C1 IEAZSLKYQNZPRN-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000012025 fluorinating agent Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 239000008297 liquid dosage form Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 230000001624 sedative effect Effects 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- QHMQWEPBXSHHLH-UHFFFAOYSA-N sulfur tetrafluoride Chemical compound FS(F)(F)F QHMQWEPBXSHHLH-UHFFFAOYSA-N 0.000 description 3
- SPXBMMLIMAILLQ-UHFFFAOYSA-N (7-bromo-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl) 2,2,2-trifluoroacetate Chemical compound C12=CC(Br)=CC=C2NC(=O)C(OC(=O)C(F)(F)F)N=C1C1=CC=CC=C1 SPXBMMLIMAILLQ-UHFFFAOYSA-N 0.000 description 2
- XHPPBGZNBZMKNH-UHFFFAOYSA-N 1,2-dihydro-1,2-benzodiazepin-3-one Chemical compound C1=CC(O)=NNC2=CC=CC=C21 XHPPBGZNBZMKNH-UHFFFAOYSA-N 0.000 description 2
- ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 2
- KXDGFSQJNOOZLJ-UHFFFAOYSA-N 3-fluoro-1-methyl-7-nitro-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1C(F)C(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1 KXDGFSQJNOOZLJ-UHFFFAOYSA-N 0.000 description 2
- JWGBSFCQLZTKGI-UHFFFAOYSA-N 3-fluoro-7-nitro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)C(F)N=C1C1=CC=CC=C1 JWGBSFCQLZTKGI-UHFFFAOYSA-N 0.000 description 2
- WKCWLUOGCCLWKQ-UHFFFAOYSA-N 4-fluorotriazolo[4,5-i][1,2]benzodiazepine Chemical class FC1=CC2=CC=CN=NC2=C2C1=NN=N2 WKCWLUOGCCLWKQ-UHFFFAOYSA-N 0.000 description 2
- XWGMOOJYTZZYJE-UHFFFAOYSA-N 7-bromo-3-fluoro-5-(2-fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Br)=CC=C2NC(=O)C(F)N=C1C1=CC=CC=C1F XWGMOOJYTZZYJE-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229920003091 Methocel™ Polymers 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HEUZVDDWUFILQA-UHFFFAOYSA-N [7-bromo-5-(2-fluorophenyl)-2-oxo-1,3-dihydro-1,4-benzodiazepin-3-yl] 2,2,2-trifluoroacetate Chemical compound FC1=CC=CC=C1C1=NC(OC(=O)C(F)(F)F)C(=O)NC2=CC=C(Br)C=C12 HEUZVDDWUFILQA-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- VTUOVBVMHPBQLX-UHFFFAOYSA-N benzene heptane Chemical compound CCCCCCC.C1=CC=CC=C1.C1=CC=CC=C1 VTUOVBVMHPBQLX-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 2
- 229960003529 diazepam Drugs 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000002222 fluorine compounds Chemical class 0.000 description 2
- CTIKAHQFRQTTAY-UHFFFAOYSA-N fluoro(trimethyl)silane Chemical group C[Si](C)(C)F CTIKAHQFRQTTAY-UHFFFAOYSA-N 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 229940035363 muscle relaxants Drugs 0.000 description 2
- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 229940125723 sedative agent Drugs 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 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
- XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
- ZHYMGSPDEVXULU-UHFFFAOYSA-N 1,2-benzodiazepin-3-one Chemical class N1=NC(=O)C=CC2=CC=CC=C21 ZHYMGSPDEVXULU-UHFFFAOYSA-N 0.000 description 1
- QYXVOHOOLFKXPK-UHFFFAOYSA-N 1,2-dihydro-1,2-benzodiazepine-3-thione Chemical class C1=CC(=S)NNC2=CC=CC=C21 QYXVOHOOLFKXPK-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-MICDWDOJSA-N 1-deuteriopropan-2-one Chemical compound [2H]CC(C)=O CSCPPACGZOOCGX-MICDWDOJSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- NOXIPAREWUQUGI-UHFFFAOYSA-N 3,7-dichloro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(Cl)N=C1C1=CC=CC=C1 NOXIPAREWUQUGI-UHFFFAOYSA-N 0.000 description 1
- LVUFMEUZYQQOQT-UHFFFAOYSA-N 3-chloro-1H-1,2-benzodiazepine Chemical class ClC1=NNc2ccccc2C=C1 LVUFMEUZYQQOQT-UHFFFAOYSA-N 0.000 description 1
- AOKGQOYNOXSOLF-UHFFFAOYSA-N 3-hydroxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 AOKGQOYNOXSOLF-UHFFFAOYSA-N 0.000 description 1
- WFQPYFHXXXIGLW-UHFFFAOYSA-N 3-hydroxy-7-nitro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC([N+]([O-])=O)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 WFQPYFHXXXIGLW-UHFFFAOYSA-N 0.000 description 1
- IVUAAOBNUNMJQC-UHFFFAOYSA-N 5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC=CC=C2NC(=O)CN=C1C1=CC=CC=C1 IVUAAOBNUNMJQC-UHFFFAOYSA-N 0.000 description 1
- JMGUMKPCAAJYSF-UHFFFAOYSA-N 7-bromo-3-fluoro-5-(2-fluorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1C(F)C(=O)N(C)C2=CC=C(Br)C=C2C=1C1=CC=CC=C1F JMGUMKPCAAJYSF-UHFFFAOYSA-N 0.000 description 1
- POAUVEHBXZCMCD-UHFFFAOYSA-N 7-bromo-3-hydroxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Br)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 POAUVEHBXZCMCD-UHFFFAOYSA-N 0.000 description 1
- OHSDHROCPILTFX-UHFFFAOYSA-N 7-chloro-1-ethyl-3-hydroxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1C(O)C(=O)N(CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 OHSDHROCPILTFX-UHFFFAOYSA-N 0.000 description 1
- BEZHVROSEDMBHG-UHFFFAOYSA-N 7-chloro-3-fluoro-5-(2-fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(F)N=C1C1=CC=CC=C1F BEZHVROSEDMBHG-UHFFFAOYSA-N 0.000 description 1
- GWRSQYGARYYMQW-UHFFFAOYSA-N 7-chloro-3-fluoro-n-methyl-2-oxo-5-phenyl-3h-1,4-benzodiazepine-1-carboxamide Chemical compound N=1C(F)C(=O)N(C(=O)NC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 GWRSQYGARYYMQW-UHFFFAOYSA-N 0.000 description 1
- KOMKSSWORSXLBP-UHFFFAOYSA-N 7-chloro-5-(2-chlorophenyl)-3-fluoro-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(F)N=C1C1=CC=CC=C1Cl KOMKSSWORSXLBP-UHFFFAOYSA-N 0.000 description 1
- FERBACJQVQVCKH-UHFFFAOYSA-N 7-chloro-5-(2-fluorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1F FERBACJQVQVCKH-UHFFFAOYSA-N 0.000 description 1
- CLYGEYKQTZVVRB-UHFFFAOYSA-N 7-chloro-n-ethyl-3-fluoro-2-oxo-5-phenyl-3h-1,4-benzodiazepine-1-carboxamide Chemical compound N=1C(F)C(=O)N(C(=O)NCC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 CLYGEYKQTZVVRB-UHFFFAOYSA-N 0.000 description 1
- KEXKHZGHQSTONH-UHFFFAOYSA-N 8-chloro-4-fluoro-1-methyl-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2C(F)N=C1C1=CC=CC=C1 KEXKHZGHQSTONH-UHFFFAOYSA-N 0.000 description 1
- YMFVFXRJBXGETJ-UHFFFAOYSA-N 8-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC=C(Cl)C=C2NC(=O)C(O)N=C1C1=CC=CC=C1Cl YMFVFXRJBXGETJ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- BIPWOEUPDFDHQV-UHFFFAOYSA-N C12=CC(Br)=CC=C2NC(=O)C[N+]([O-])=C1C1=CC=CC=C1F Chemical compound C12=CC(Br)=CC=C2NC(=O)C[N+]([O-])=C1C1=CC=CC=C1F BIPWOEUPDFDHQV-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 206010053398 Clonic convulsion Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-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
- RMFYWNFETXNTIQ-UHFFFAOYSA-N Flutemazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F RMFYWNFETXNTIQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- JOOMLFKONHCLCJ-UHFFFAOYSA-N N-(trimethylsilyl)diethylamine Chemical compound CCN(CC)[Si](C)(C)C JOOMLFKONHCLCJ-UHFFFAOYSA-N 0.000 description 1
- 229910004013 NO 2 Inorganic materials 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 229910007161 Si(CH3)3 Inorganic materials 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-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
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- HQNIJHRMGXERBP-UHFFFAOYSA-N chembl1611846 Chemical compound C12=CC(Br)=CC=C2NC(=O)C[N+]([O-])=C1C1=CC=CC=C1 HQNIJHRMGXERBP-UHFFFAOYSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- UVCOILFBWYKHHB-UHFFFAOYSA-N desalkylflurazepam Chemical compound FC1=CC=CC=C1C1=NCC(=O)NC2=CC=C(Cl)C=C12 UVCOILFBWYKHHB-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000011152 fibreglass Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000002221 fluorine Chemical class 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- SAADBVWGJQAEFS-UHFFFAOYSA-N flurazepam Chemical compound N=1CC(=O)N(CCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F SAADBVWGJQAEFS-UHFFFAOYSA-N 0.000 description 1
- 229960003528 flurazepam Drugs 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- 125000002346 iodo group Chemical group I* 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
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 229910001509 metal bromide Inorganic materials 0.000 description 1
- 229910001510 metal chloride Inorganic materials 0.000 description 1
- 229910001512 metal fluoride Inorganic materials 0.000 description 1
- 229910001511 metal iodide Inorganic materials 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 229960004715 morphine sulfate Drugs 0.000 description 1
- GRVOTVYEFDAHCL-RTSZDRIGSA-N morphine sulfate pentahydrate Chemical compound O.O.O.O.O.OS(O)(=O)=O.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O GRVOTVYEFDAHCL-RTSZDRIGSA-N 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- SAVQQRYWWAGSQW-UHFFFAOYSA-N n-methyl-n-(trifluoro-$l^{4}-sulfanyl)methanamine Chemical compound CN(C)S(F)(F)F SAVQQRYWWAGSQW-UHFFFAOYSA-N 0.000 description 1
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 1
- 229960001454 nitrazepam Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 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
- 229960004535 oxazepam Drugs 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 229940096017 silver fluoride Drugs 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- LSJNBGSOIVSBBR-UHFFFAOYSA-N thionyl fluoride Chemical compound FS(F)=O LSJNBGSOIVSBBR-UHFFFAOYSA-N 0.000 description 1
- CCKAYTBOIIPZGA-UHFFFAOYSA-N trifluoro(pyrrolidin-1-yl)-$l^{4}-sulfane Chemical compound FS(F)(F)N1CCCC1 CCKAYTBOIIPZGA-UHFFFAOYSA-N 0.000 description 1
- 230000003313 weakening effect Effects 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
-
- 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
-
- 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
- C07D243/24—Oxygen atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (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)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59750275A | 1975-07-21 | 1975-07-21 | |
| US05/687,318 US4246270A (en) | 1976-05-26 | 1976-05-26 | 3-Fluorobenzodiazepines and compositions and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO762525L true NO762525L (cs) | 1977-01-24 |
Family
ID=27082840
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO762525A NO762525L (cs) | 1975-07-21 | 1976-07-20 |
Country Status (22)
| Country | Link |
|---|---|
| JP (1) | JPS5231087A (cs) |
| AR (1) | AR211547A1 (cs) |
| AU (1) | AU512991B2 (cs) |
| CH (1) | CH598234A5 (cs) |
| DD (1) | DD126767A5 (cs) |
| DE (1) | DE2632539A1 (cs) |
| DK (1) | DK326576A (cs) |
| ES (1) | ES449960A1 (cs) |
| FI (1) | FI762079A7 (cs) |
| FR (1) | FR2318643A1 (cs) |
| GB (1) | GB1553599A (cs) |
| GR (1) | GR60850B (cs) |
| IL (1) | IL50072A0 (cs) |
| LU (1) | LU75411A1 (cs) |
| MX (1) | MX3412E (cs) |
| NL (1) | NL7608074A (cs) |
| NO (1) | NO762525L (cs) |
| NZ (1) | NZ181516A (cs) |
| PH (1) | PH12173A (cs) |
| PT (1) | PT65383B (cs) |
| SE (1) | SE7606676L (cs) |
| SU (1) | SU683618A3 (cs) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4182760A (en) * | 1977-06-16 | 1980-01-08 | E. I. Du Pont De Nemours And Company | Benzophenone anti-oximes, diazepin-N-oxides, and their use as pharmaceutical agents and as intermediates for pharmaceutical agents |
| JP2527717Y2 (ja) * | 1991-07-19 | 1997-03-05 | 株式会社デンソー | 車両用計器の取付け構造 |
-
1976
- 1976-06-11 SE SE7606676A patent/SE7606676L/xx unknown
- 1976-07-19 PT PT65383A patent/PT65383B/pt unknown
- 1976-07-19 LU LU75411A patent/LU75411A1/xx unknown
- 1976-07-19 AU AU15988/76A patent/AU512991B2/en not_active Expired
- 1976-07-19 FI FI762079A patent/FI762079A7/fi not_active Application Discontinuation
- 1976-07-20 CH CH929576A patent/CH598234A5/xx not_active IP Right Cessation
- 1976-07-20 FR FR7622085A patent/FR2318643A1/fr active Granted
- 1976-07-20 NO NO762525A patent/NO762525L/no unknown
- 1976-07-20 PH PH18705A patent/PH12173A/en unknown
- 1976-07-20 NZ NZ181516A patent/NZ181516A/xx unknown
- 1976-07-20 MX MX001783U patent/MX3412E/es unknown
- 1976-07-20 DE DE19762632539 patent/DE2632539A1/de not_active Withdrawn
- 1976-07-20 SU SU762384509A patent/SU683618A3/ru active
- 1976-07-20 IL IL50072A patent/IL50072A0/xx unknown
- 1976-07-20 AR AR264001A patent/AR211547A1/es active
- 1976-07-20 DD DD193980A patent/DD126767A5/xx unknown
- 1976-07-20 GB GB30200/76A patent/GB1553599A/en not_active Expired
- 1976-07-20 DK DK326576A patent/DK326576A/da unknown
- 1976-07-20 ES ES449960A patent/ES449960A1/es not_active Expired
- 1976-07-21 GR GR51314A patent/GR60850B/el unknown
- 1976-07-21 JP JP51087698A patent/JPS5231087A/ja active Pending
- 1976-07-21 NL NL7608074A patent/NL7608074A/xx not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5231087A (en) | 1977-03-09 |
| NZ181516A (en) | 1978-04-28 |
| GR60850B (en) | 1978-08-31 |
| PT65383A (en) | 1976-08-01 |
| CH598234A5 (cs) | 1978-04-28 |
| FR2318643A1 (fr) | 1977-02-18 |
| MX3412E (es) | 1980-11-06 |
| SU683618A3 (ru) | 1979-08-30 |
| DE2632539A1 (de) | 1977-02-10 |
| GB1553599A (en) | 1979-09-26 |
| IL50072A0 (en) | 1976-09-30 |
| AR211547A1 (es) | 1978-01-30 |
| AU512991B2 (en) | 1980-11-06 |
| FI762079A7 (cs) | 1977-01-22 |
| AU1598876A (en) | 1978-01-26 |
| FR2318643B1 (cs) | 1980-10-17 |
| NL7608074A (nl) | 1977-01-25 |
| ES449960A1 (es) | 1977-12-01 |
| LU75411A1 (cs) | 1978-02-08 |
| DD126767A5 (cs) | 1977-08-10 |
| SE7606676L (sv) | 1977-01-22 |
| PT65383B (en) | 1978-06-08 |
| DK326576A (da) | 1977-01-22 |
| PH12173A (en) | 1978-11-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60119719T2 (de) | Neue aza-indolyl derivate | |
| DE69735891T2 (de) | Pyridon-kondensierte azabicyclische- oder cytisinderivate, ihre herstellung und verwendung in der suchttherapie | |
| EP0059390B1 (de) | Imidazodiazepine, Zwischenprodukte und Verfahren für ihre Herstellung, sowie diese enthaltende Arzneimittel | |
| DE2203782A1 (de) | Verfahren zur Herstellung von Triazolobenzodiazepinen sowie neue Triazolobenzodiazepine und deren Zwischenprodukte | |
| EP0027214A1 (de) | Imidazodiazepin-Derivate, Verfahren und Zwischenprodukte zu ihrer Herstellung, diese enthaltende Arzneimittel und deren therapeutische Verwendung | |
| EP0059387A2 (de) | Imidazodiazepine, Verfahren und Zwischenprodukte zu ihrer Herstellung, sowie diese enthaltende Arzneimittel | |
| BRPI0616767A2 (pt) | derivados de pirazolo [1,5-alfa]pirimidinila úteis como antagonistas de receptores de fatores de liberação de corticotropina (crf), composição contendo tais compostos, bem como usos | |
| DD147355A5 (de) | Verfahren zur herstellung von merkapto-substituierten 2,3,4,5-tetrahydro-1h-3-benzazepinen | |
| KR20010087361A (ko) | [1,2,4]트리아졸로[1,5-ｃ]피리미딘 유도체 | |
| DD151754A5 (de) | Pyrazolochinoline,verfahren zu ihrer herstellung,pharmazeutische praeparate enthaltend diese verbindungen,sowie ihre therapeutische verwendung | |
| TWI377195B (en) | Tricyclic indeno-pyrrole derivatives as serotonin receptor modulators | |
| HUP0002650A2 (hu) | 4-Oxo-3,5-dihidro-4H-piridazino[4,5-b]-indol-1-acetamid-származékok, eljárás a vegyületek előállítására és a vegyületeket tartalmazó gyógyszerkészítmények | |
| NO762525L (cs) | ||
| Wright Jr et al. | Derivatives of 11-(1-piperazinyl)-5H-pyrrolo [2, 1-c][1, 4] benzodiazepine as central nervous system agents | |
| US4587245A (en) | Method of treating neuropsychic disturbances by benzodiazepine derivatives and composition therefor | |
| DE2220739A1 (de) | Neue in 1-Stellung substituierte 6-Phenyl-4H-s-triazolo [4,3-a][1,4] benzodiazepine und Verfahren zu ihrer Herstellung | |
| US4246270A (en) | 3-Fluorobenzodiazepines and compositions and uses thereof | |
| US4182760A (en) | Benzophenone anti-oximes, diazepin-N-oxides, and their use as pharmaceutical agents and as intermediates for pharmaceutical agents | |
| US5317018A (en) | Benzodiazepines and compositions for treating anxiety and panic disorders, and idiopathic and psychomotor epilepsy | |
| DE2002882A1 (de) | Benzodiazepin-Derivate | |
| DE2456311A1 (de) | Benzodiazepinderivate | |
| EP0072029B1 (de) | Triazolobenzazepine, Verfahren und Zwischenprodukte zu deren Herstellung und diese enthaltende Arzneimittel | |
| JPS6228144B2 (cs) | ||
| DE60213113T2 (de) | 7-TERT-BUTYL-3-(2-FLUOROPHENYL)-6-(2H-i1,2,4öTRIAZOL-3-YLMETHOXY)-i1,2,4öTRIAZOLOi4,3-BöPYRIDAZIN FÜR DIE BEHANDLUNG VON ANGSTZUSTÄNDEN UND KRÄMPFEN | |
| JPS584034B2 (ja) | ６−フエニル−ｓ−トリアゾロ〔４，３−ａ〕〔１，３，４〕ベンゾトリアゼピン類の製造法 |