NO843376L - Benzodiazepinderivater - Google Patents
BenzodiazepinderivaterInfo
- Publication number
- NO843376L NO843376L NO843376A NO843376A NO843376L NO 843376 L NO843376 L NO 843376L NO 843376 A NO843376 A NO 843376A NO 843376 A NO843376 A NO 843376A NO 843376 L NO843376 L NO 843376L
- Authority
- NO
- Norway
- Prior art keywords
- benzodiazepine
- chlorophenyl
- imidazo
- formula
- methylene chloride
- Prior art date
Links
- 229940049706 benzodiazepine Drugs 0.000 title description 10
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims description 133
- -1 amino compound Chemical class 0.000 claims description 53
- VUMCYGBPHCVIAY-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carboxamide Chemical compound NC(=O)C1=NNc2ccccc2C=C1 VUMCYGBPHCVIAY-UHFFFAOYSA-N 0.000 claims description 52
- BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 239000007858 starting material Substances 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- 150000008064 anhydrides Chemical class 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 125000001589 carboacyl group Chemical group 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 5
- KLNFAMGHSZQYHR-UHFFFAOYSA-N imidazo[4,5-i][1,2]benzodiazepine Chemical class C1=CC=NN=C2C3=NC=NC3=CC=C21 KLNFAMGHSZQYHR-UHFFFAOYSA-N 0.000 claims description 4
- 238000012546 transfer Methods 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 372
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 214
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 207
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 129
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 120
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 112
- 239000000243 solution Substances 0.000 description 105
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- 239000013078 crystal Substances 0.000 description 73
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 70
- 239000000203 mixture Substances 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 56
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 47
- 239000002904 solvent Substances 0.000 description 44
- 239000000047 product Substances 0.000 description 41
- 238000002425 crystallisation Methods 0.000 description 39
- 230000008025 crystallization Effects 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
- 125000004494 ethyl ester group Chemical group 0.000 description 31
- 238000003756 stirring Methods 0.000 description 30
- 229960000583 acetic acid Drugs 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 28
- 229910021529 ammonia Inorganic materials 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 23
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- 238000010992 reflux Methods 0.000 description 21
- 239000000538 analytical sample Substances 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 19
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
- LJGKKJWPDGDDEH-UHFFFAOYSA-N ethyl 1H-1,2-benzodiazepine-3-carboxylate Chemical compound C(C)OC(=O)C1=NNC2=C(C=C1)C=CC=C2 LJGKKJWPDGDDEH-UHFFFAOYSA-N 0.000 description 18
- 238000001953 recrystallisation Methods 0.000 description 18
- 239000012362 glacial acetic acid Substances 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 16
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 16
- 239000002253 acid Substances 0.000 description 15
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000007868 Raney catalyst Substances 0.000 description 12
- 229910000564 Raney nickel Inorganic materials 0.000 description 12
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 12
- 150000001450 anions Chemical class 0.000 description 12
- 239000000155 melt Substances 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 10
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 10
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- ONOBXDPYDHTSBQ-UHFFFAOYSA-N 2,3,4,7-tetrahydro-1h-diazepine Chemical compound C1CC=CCNN1 ONOBXDPYDHTSBQ-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 229910052783 alkali metal Inorganic materials 0.000 description 8
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 230000008020 evaporation Effects 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 235000010288 sodium nitrite Nutrition 0.000 description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 230000000949 anxiolytic effect Effects 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- MZHUTGQZAZLFKW-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carboxylic acid Chemical compound C1=CC(C(=O)O)=NNC2=CC=CC=C21 MZHUTGQZAZLFKW-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 229910000831 Steel Inorganic materials 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 150000002170 ethers Chemical class 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000003825 pressing Methods 0.000 description 6
- 239000010959 steel Substances 0.000 description 6
- TWMOGFVGTHATIV-UHFFFAOYSA-N 2-(chloromethyl)-4-(2-chlorophenyl)-3-oxidoquinazolin-3-ium Chemical compound [O-][N+]1=C(CCl)N=C2C=CC=CC2=C1C1=CC=CC=C1Cl TWMOGFVGTHATIV-UHFFFAOYSA-N 0.000 description 5
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- FPULFENIJDPZBX-UHFFFAOYSA-N ethyl 2-isocyanoacetate Chemical compound CCOC(=O)C[N+]#[C-] FPULFENIJDPZBX-UHFFFAOYSA-N 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000012467 final product Substances 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 5
- 238000007034 nitrosation reaction Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 4
- 150000001204 N-oxides Chemical class 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 150000003973 alkyl amines Chemical class 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical group [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 239000001632 sodium acetate Substances 0.000 description 4
- 235000017281 sodium acetate Nutrition 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 229910052720 vanadium Inorganic materials 0.000 description 4
- HIRDYLVKLLGUTQ-UHFFFAOYSA-N (2-amino-4-chlorophenyl)-(2-chlorophenyl)methanone Chemical compound NC1=CC(Cl)=CC=C1C(=O)C1=CC=CC=C1Cl HIRDYLVKLLGUTQ-UHFFFAOYSA-N 0.000 description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 3
- QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 3
- ZNBNBTIDJSKEAM-UHFFFAOYSA-N 4-[7-hydroxy-2-[5-[5-[6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]-5-methyloxolan-2-yl]-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-2-methyl-3-propanoyloxypentanoic acid Chemical compound C1C(O)C(C)C(C(C)C(OC(=O)CC)C(C)C(O)=O)OC11OC(C)(C2OC(C)(CC2)C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CC1 ZNBNBTIDJSKEAM-UHFFFAOYSA-N 0.000 description 3
- HHEYPEZKVASXFW-UHFFFAOYSA-N 5-(2-bromophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound BrC1=CC=CC=C1C1=NCC(=O)NC2=CC=CC=C12 HHEYPEZKVASXFW-UHFFFAOYSA-N 0.000 description 3
- DXAIBZTWPCDCFJ-UHFFFAOYSA-N 5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound ClC1=CC=CC=C1C1=NCC(=O)NC2=CC=CC=C12 DXAIBZTWPCDCFJ-UHFFFAOYSA-N 0.000 description 3
- IFCPYKRHAGUXOQ-UHFFFAOYSA-N 6-fluoro-3-(2-fluorophenyl)-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC(F)=CC=C2C=1C1=CC=CC=C1F IFCPYKRHAGUXOQ-UHFFFAOYSA-N 0.000 description 3
- SVDYIODNHANAPQ-UHFFFAOYSA-N 6-fluoro-3-(2-fluorophenyl)-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(F)=CC=C2C=1C1=CC=CC=C1F SVDYIODNHANAPQ-UHFFFAOYSA-N 0.000 description 3
- RRSKLMXUNFCGKD-UHFFFAOYSA-N 7-chloro-2-(chloromethyl)-4-(2-chlorophenyl)-3-oxidoquinazolin-3-ium Chemical compound [O-][N+]1=C(CCl)N=C2C=C(Cl)C=CC2=C1C1=CC=CC=C1Cl RRSKLMXUNFCGKD-UHFFFAOYSA-N 0.000 description 3
- BYVWCFBXIBXYES-UHFFFAOYSA-N 8-fluoro-5-(2-fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C=1C(F)=CC=C2C=1NC(=O)CN=C2C1=CC=CC=C1F BYVWCFBXIBXYES-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 3
- NASVANHOMILYPU-UHFFFAOYSA-N [3-(2-chlorophenyl)-6-fluoro-1h-indol-2-yl]methanamine;hydrochloride Chemical compound Cl.NCC=1NC2=CC(F)=CC=C2C=1C1=CC=CC=C1Cl NASVANHOMILYPU-UHFFFAOYSA-N 0.000 description 3
- KWHXHQUWPIEXNC-UHFFFAOYSA-N [O-][N+]1=C(C2=CC=CC=C2NC(=O)C1)C1=C(Cl)C=CC=C1 Chemical compound [O-][N+]1=C(C2=CC=CC=C2NC(=O)C1)C1=C(Cl)C=CC=C1 KWHXHQUWPIEXNC-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 238000007098 aminolysis reaction Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 3
- 230000036461 convulsion Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- MTRGCJCFSCFWDX-UHFFFAOYSA-N dimethyl 2-[1-[5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-ylidene]ethyl]propanedioate Chemical compound COC(=O)C(C(C)=C1NC2=C(C(=NC1)C1=C(C=CC=C1)Cl)C=CC=C2)C(=O)OC MTRGCJCFSCFWDX-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
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- 239000000839 emulsion Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- FNRDGGCCHSQRDN-UHFFFAOYSA-N ethyl 2-[(2-chlorophenyl)methyl]-3-oxobutanoate Chemical compound CCOC(=O)C(C(C)=O)CC1=CC=CC=C1Cl FNRDGGCCHSQRDN-UHFFFAOYSA-N 0.000 description 1
- MVBIGMCOCKSWND-UHFFFAOYSA-N ethyl 3-(2-chlorophenyl)-6-fluoro-1H-indole-2-carboxylate Chemical compound C(C)OC(=O)C=1NC2=CC(=CC=C2C=1C1=C(C=CC=C1)Cl)F MVBIGMCOCKSWND-UHFFFAOYSA-N 0.000 description 1
- WORDLRGQGWENBO-UHFFFAOYSA-N ethyl 6-(2-chlorophenyl)-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound CCOC(=O)C=1N=CN(C2=CC=CC=C22)C=1CN=C2C1=CC=CC=C1Cl WORDLRGQGWENBO-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- XQELSYTZKFGZEL-UHFFFAOYSA-N methyl 2-[(2-fluorophenyl)methyl]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)CC1=CC=CC=C1F XQELSYTZKFGZEL-UHFFFAOYSA-N 0.000 description 1
- GFUACTZSLJVREI-UHFFFAOYSA-N methyl 2-[5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2-yl]-2-hydroxyiminoacetate Chemical compound COC(C(C1=NC2=C(C(=NC1)C1=C(C=CC=C1)Cl)C=CC=C2)=NO)=O GFUACTZSLJVREI-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical class COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- BLLFVUPNHCTMSV-UHFFFAOYSA-N methyl nitrite Chemical compound CON=O BLLFVUPNHCTMSV-UHFFFAOYSA-N 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 230000036225 muscular coordination Effects 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- MUMVIYLVHVCYGI-UHFFFAOYSA-N n,n,n',n',n",n"-hexamethylmethanetriamine Chemical compound CN(C)C(N(C)C)N(C)C MUMVIYLVHVCYGI-UHFFFAOYSA-N 0.000 description 1
- GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- CZPZWMPYEINMCF-UHFFFAOYSA-N propaneperoxoic acid Chemical compound CCC(=O)OO CZPZWMPYEINMCF-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 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
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003511 tertiary amides Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 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
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
- C07D239/76—N-oxides
-
- 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
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Anesthesiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52619483A | 1983-08-25 | 1983-08-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO843376L true NO843376L (no) | 1985-02-26 |
Family
ID=24096318
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO843376A NO843376L (no) | 1983-08-25 | 1984-08-23 | Benzodiazepinderivater |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0135770A3 (fr) |
| JP (1) | JPS6067480A (fr) |
| KR (1) | KR850001756A (fr) |
| AU (1) | AU3237984A (fr) |
| DK (1) | DK406384A (fr) |
| ES (2) | ES535392A0 (fr) |
| FI (1) | FI843356A (fr) |
| GR (1) | GR80197B (fr) |
| HU (1) | HU193588B (fr) |
| IL (1) | IL72757A0 (fr) |
| MC (1) | MC1616A1 (fr) |
| NO (1) | NO843376L (fr) |
| NZ (1) | NZ209316A (fr) |
| PH (1) | PH20029A (fr) |
| PT (1) | PT79131B (fr) |
| ZA (1) | ZA845757B (fr) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL91418A (en) * | 1988-09-01 | 1997-11-20 | Rhone Poulenc Agrochimie | (hetero) cyclic amide derivatives, process for their preparation and fungicidal compositions containing them |
| FR2635776B1 (fr) * | 1988-09-01 | 1993-06-11 | Rhone Poulenc Agrochimie | Derives amides, procede pour leur fabrication et compositions fongicides les contenant |
| US5317018A (en) * | 1992-06-09 | 1994-05-31 | Armin Walser | Benzodiazepines and compositions for treating anxiety and panic disorders, and idiopathic and psychomotor epilepsy |
| TW234123B (fr) * | 1992-12-16 | 1994-11-11 | Takeda Pharm Industry Co Ltd | |
| US6063921A (en) | 1997-11-20 | 2000-05-16 | Pharm-Eco Laboratories, Inc. | Synthesis of 11-aryl-5,6-dihydro-11H-dibenz[b,e]azepines |
| US8119629B2 (en) | 2007-10-03 | 2012-02-21 | Bristol-Meyers Squibb Company | Carboxamide GABAA α2 modulators |
| BR112019003065A2 (pt) | 2016-08-16 | 2019-05-21 | The Trustees Of Columbia University In The City Of New York | moduladores do receptor gaba(a) e métodos para o controle da hiper-responsividade das vias respiratórias e inflamação na asma |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA755418B (en) * | 1974-09-11 | 1977-06-29 | Hoffmann La Roche | Diazepine derivatives |
| AU509371B2 (en) * | 1975-08-07 | 1980-05-08 | F. Hoffmann-La Roche Ag | Diazepine Derivatives |
| US4125726A (en) * | 1977-03-11 | 1978-11-14 | Hoffmann-La Roche Inc. | Imidazo[1,5-a][1,4]benzodiazepines |
| DK151808C (da) * | 1982-11-16 | 1988-06-20 | Ferrosan As | Analogifremgangsmaade til fremstilling af oxadiazolylimidazo-oe1,4aa-benzodiazepinderivater |
-
1984
- 1984-07-25 ZA ZA845757A patent/ZA845757B/xx unknown
- 1984-08-13 EP EP84109639A patent/EP0135770A3/fr not_active Withdrawn
- 1984-08-23 NZ NZ209316A patent/NZ209316A/en unknown
- 1984-08-23 MC MC841721A patent/MC1616A1/fr unknown
- 1984-08-23 NO NO843376A patent/NO843376L/no unknown
- 1984-08-23 GR GR80197A patent/GR80197B/el unknown
- 1984-08-23 IL IL72757A patent/IL72757A0/xx unknown
- 1984-08-24 FI FI843356A patent/FI843356A/fi not_active Application Discontinuation
- 1984-08-24 DK DK406384A patent/DK406384A/da not_active Application Discontinuation
- 1984-08-24 JP JP59175328A patent/JPS6067480A/ja active Pending
- 1984-08-24 AU AU32379/84A patent/AU3237984A/en not_active Abandoned
- 1984-08-24 ES ES535392A patent/ES535392A0/es active Granted
- 1984-08-24 PH PH31144A patent/PH20029A/en unknown
- 1984-08-24 KR KR1019840005134A patent/KR850001756A/ko not_active Application Discontinuation
- 1984-08-24 HU HU843179A patent/HU193588B/hu unknown
- 1984-08-24 PT PT79131A patent/PT79131B/pt unknown
-
1985
- 1985-05-31 ES ES543717A patent/ES8603433A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| PT79131A (en) | 1984-09-01 |
| DK406384D0 (da) | 1984-08-24 |
| NZ209316A (en) | 1987-04-30 |
| FI843356A (fi) | 1985-02-26 |
| KR850001756A (ko) | 1985-04-01 |
| IL72757A0 (en) | 1984-11-30 |
| HU193588B (en) | 1987-10-28 |
| AU3237984A (en) | 1985-02-28 |
| JPS6067480A (ja) | 1985-04-17 |
| EP0135770A3 (fr) | 1988-01-13 |
| DK406384A (da) | 1985-02-26 |
| MC1616A1 (fr) | 1985-07-18 |
| EP0135770A2 (fr) | 1985-04-03 |
| GR80197B (en) | 1985-01-03 |
| FI843356A0 (fi) | 1984-08-24 |
| PH20029A (en) | 1986-09-04 |
| ES543717A0 (es) | 1986-01-01 |
| ES8602700A1 (es) | 1985-12-01 |
| ZA845757B (en) | 1985-04-24 |
| ES535392A0 (es) | 1985-12-01 |
| HUT34978A (en) | 1985-05-28 |
| ES8603433A1 (es) | 1986-01-01 |
| PT79131B (en) | 1986-11-14 |
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