NZ195071A - Imidazo(1,4)diazepines - Google Patents
Imidazo(1,4)diazepinesInfo
- Publication number
- NZ195071A NZ195071A NZ195071A NZ19507180A NZ195071A NZ 195071 A NZ195071 A NZ 195071A NZ 195071 A NZ195071 A NZ 195071A NZ 19507180 A NZ19507180 A NZ 19507180A NZ 195071 A NZ195071 A NZ 195071A
- Authority
- NZ
- New Zealand
- Prior art keywords
- methyl
- ethyl
- imidazo
- benzodiazepine
- oxo
- Prior art date
Links
- NFSSFSUDARPYCE-UHFFFAOYSA-N imidazo[4,5-e][1,4]diazepine Chemical class N1=CC=NC2=NC=NC2=C1 NFSSFSUDARPYCE-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 194
- 239000000203 mixture Substances 0.000 claims description 176
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 139
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 239000001257 hydrogen Substances 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 239000002253 acid Substances 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 36
- 238000004519 manufacturing process Methods 0.000 claims description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 27
- 230000000694 effects Effects 0.000 claims description 25
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- 150000002431 hydrogen Chemical group 0.000 claims description 16
- -1 Ethyl (R,S) Chemical compound 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- OFBIFZUFASYYRE-UHFFFAOYSA-N flumazenil Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OCC)=C21 OFBIFZUFASYYRE-UHFFFAOYSA-N 0.000 claims description 14
- 125000006410 propenylene group Chemical group 0.000 claims description 14
- 229920002261 Corn starch Polymers 0.000 claims description 13
- 235000019759 Maize starch Nutrition 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- HNGRWUCKESPKRC-UHFFFAOYSA-N ethyl 5-methyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound C1N(C)C(=O)C2=CC=CC=C2N2C=NC(C(=O)OCC)=C21 HNGRWUCKESPKRC-UHFFFAOYSA-N 0.000 claims description 11
- 150000001721 carbon Chemical group 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 229910052736 halogen Chemical group 0.000 claims description 10
- 150000002367 halogens Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 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 claims description 9
- 239000008101 lactose Substances 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 206010003591 Ataxia Diseases 0.000 claims description 8
- 239000013543 active substance Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 230000001977 ataxic effect Effects 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 7
- 210000004369 blood Anatomy 0.000 claims description 7
- 239000003874 central nervous system depressant Substances 0.000 claims description 7
- 239000003158 myorelaxant agent Substances 0.000 claims description 7
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000002560 nitrile group Chemical group 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 239000000460 chlorine Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- OODGJVJCBIXWFZ-UHFFFAOYSA-N ethyl 5-methyl-6-sulfanylidene-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound C1N(C)C(=S)C2=CC=CC=C2N2C=NC(C(=O)OCC)=C21 OODGJVJCBIXWFZ-UHFFFAOYSA-N 0.000 claims description 4
- QZZWDAILXQWHAG-UHFFFAOYSA-N methyl 5-methyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound C1N(C)C(=O)C2=CC=CC=C2N2C=NC(C(=O)OC)=C21 QZZWDAILXQWHAG-UHFFFAOYSA-N 0.000 claims description 4
- CEHKKWWXELBNPS-UHFFFAOYSA-N 1,4-benzodiazepine-1-carboxylic acid Chemical compound OC(=O)N1C=CN=CC2=CC=CC=C12 CEHKKWWXELBNPS-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 125000005518 carboxamido group Chemical group 0.000 claims description 3
- NTYBXVOZFGOCCH-UHFFFAOYSA-N chembl6752 Chemical compound COC(=O)C=1N=CN2C=1CN(C)C(=O)C1=C2C=CS1 NTYBXVOZFGOCCH-UHFFFAOYSA-N 0.000 claims description 3
- CGRSAXYBERPUMA-VIFPVBQESA-N ethyl (s)-10,11,12,12a-tetrahydro-8-oxo-8h-imidazo[5,1-c]pyrrolo[1,2-a]thieno[3,2-e][1,4]diazepine-1-carboxylate Chemical compound O=C1N2CCC[C@H]2C2=C(C(=O)OCC)N=CN2C2=C1SC=C2 CGRSAXYBERPUMA-VIFPVBQESA-N 0.000 claims description 3
- HQGUQOHSCRHEFJ-LBPRGKRZSA-N ethyl (s)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9h-imidazo[1,5-a]pyrrolo[2,1-c][1,4]-benzodiazepine-1-carboxylate Chemical compound O=C1C2=C(Cl)C=CC=C2N2C=NC(C(=O)OCC)=C2[C@@H]2CCCN21 HQGUQOHSCRHEFJ-LBPRGKRZSA-N 0.000 claims description 3
- AXJSHWLLFIXJIM-UHFFFAOYSA-N ethyl 5,6-dihydro-5-methyl-6-oxo-4h-imidazo[1,5-a]thieno[2,3-f][1,4]-diazepine-3-carboxylate Chemical compound CCOC(=O)C=1N=CN2C=1CN(C)C(=O)C1=C2C=CS1 AXJSHWLLFIXJIM-UHFFFAOYSA-N 0.000 claims description 3
- QODUFNRDAZCDEE-UHFFFAOYSA-N ethyl 5,7-dimethyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound C1N(C)C(=O)C2=C(C)C=CC=C2N2C=NC(C(=O)OCC)=C21 QODUFNRDAZCDEE-UHFFFAOYSA-N 0.000 claims description 3
- BMGXAZCDDYTVFV-UHFFFAOYSA-N imidazo[4,5-c]diazepine Chemical class C1=CN=NC2=NC=NC2=C1 BMGXAZCDDYTVFV-UHFFFAOYSA-N 0.000 claims description 3
- HEOKNRFBEQLCFZ-QMMMGPOBSA-N methyl (s)-10,11,12,12a-tetrahydro-8-oxo-8h-imidazo[5,1-c]pyrrolo[1,2-a]thieno[3,2-e][1,4]diazepine-1-carboxylate Chemical compound O=C1N2CCC[C@H]2C2=C(C(=O)OC)N=CN2C2=C1SC=C2 HEOKNRFBEQLCFZ-QMMMGPOBSA-N 0.000 claims description 3
- 125000003544 oxime group Chemical group 0.000 claims description 3
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 3
- FXQNZTDCYMIXQP-ZDUSSCGKSA-N (s)-11,12,13,13a-tetrahydro-9-oxo-9h-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carbonitrile Chemical compound O=C1N2CCC[C@H]2C2=C(C#N)N=CN2C2=CC=CC=C12 FXQNZTDCYMIXQP-ZDUSSCGKSA-N 0.000 claims description 2
- HLMAWKYTEWBRHV-UHFFFAOYSA-N 8-fluoro-5-methyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carbonitrile Chemical compound O=C1N(C)CC2=C(C#N)N=CN2C2=CC=C(F)C=C21 HLMAWKYTEWBRHV-UHFFFAOYSA-N 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- YKRYEHIEQKEGRG-ZDUSSCGKSA-N chembl2314840 Chemical compound O=C1C2=CC(F)=CC=C2N2C=NC(C(=O)OCC)=C2[C@@H]2CCCN21 YKRYEHIEQKEGRG-ZDUSSCGKSA-N 0.000 claims description 2
- SKGNKKNPQHEANX-UHFFFAOYSA-N ethyl 7-fluoro-5-methyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound C1N(C)C(=O)C2=C(F)C=CC=C2N2C=NC(C(=O)OCC)=C21 SKGNKKNPQHEANX-UHFFFAOYSA-N 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- WTCNIQKFPRTYES-UHFFFAOYSA-N 5-methyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carbonitrile Chemical compound O=C1N(C)CC2=C(C#N)N=CN2C2=CC=CC=C21 WTCNIQKFPRTYES-UHFFFAOYSA-N 0.000 claims 1
- WSDBAFQWNWJTNG-UHFFFAOYSA-N sarmazenil Chemical compound C1N(C)C(=O)C2=C(Cl)C=CC=C2N2C=NC(C(=O)OCC)=C21 WSDBAFQWNWJTNG-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 198
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 166
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 136
- 239000000243 solution Substances 0.000 description 121
- 238000002844 melting Methods 0.000 description 86
- 230000008018 melting Effects 0.000 description 86
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 76
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 75
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 43
- 238000009835 boiling Methods 0.000 description 39
- 238000001953 recrystallisation Methods 0.000 description 39
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 38
- 235000019341 magnesium sulphate Nutrition 0.000 description 38
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 36
- 229910052700 potassium Inorganic materials 0.000 description 36
- 239000011591 potassium Substances 0.000 description 36
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 35
- 235000019441 ethanol Nutrition 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- 229960000583 acetic acid Drugs 0.000 description 28
- 238000001816 cooling Methods 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 238000010992 reflux Methods 0.000 description 25
- FPULFENIJDPZBX-UHFFFAOYSA-N ethyl 2-isocyanoacetate Chemical compound CCOC(=O)C[N+]#[C-] FPULFENIJDPZBX-UHFFFAOYSA-N 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 22
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 239000012071 phase Substances 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 16
- 239000012300 argon atmosphere Substances 0.000 description 16
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 16
- 229910000104 sodium hydride Inorganic materials 0.000 description 16
- 239000012312 sodium hydride Substances 0.000 description 16
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 14
- 239000013078 crystal Substances 0.000 description 14
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 229960004424 carbon dioxide Drugs 0.000 description 11
- 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 11
- 229960003529 diazepam Drugs 0.000 description 11
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- 239000002585 base Substances 0.000 description 10
- 235000011089 carbon dioxide Nutrition 0.000 description 10
- VUSVWZBQTTWZGJ-ZDUSSCGKSA-N ethyl (s)-11,12,13,13a-tetrahydro-9-oxo-9h-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate Chemical compound O=C1C2=CC=CC=C2N2C=NC(C(=O)OCC)=C2[C@@H]2CCCN21 VUSVWZBQTTWZGJ-ZDUSSCGKSA-N 0.000 description 10
- 239000004533 oil dispersion Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 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 8
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- 239000002026 chloroform extract Substances 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 7
- 108010077895 Sarcosine Proteins 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 229960002200 flunitrazepam Drugs 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 229940043230 sarcosine Drugs 0.000 description 7
- 230000001843 schistosomicidal effect Effects 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 241000699800 Cricetinae Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 230000033764 rhythmic process Effects 0.000 description 6
- 239000000829 suppository Substances 0.000 description 6
- HZABUXCSZMLBHU-UHFFFAOYSA-N 1H-1,4-benzodiazepine-3-carboxylic acid Chemical compound C1=NC(C(=O)O)=CNC2=CC=CC=C21 HZABUXCSZMLBHU-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 229940093476 ethylene glycol Drugs 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 239000012448 Lithium borohydride Substances 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
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- 239000000796 flavoring agent Substances 0.000 description 1
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- 210000001320 hippocampus Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
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- 229960004903 invert sugar Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- SZAVVKVUMPLRRS-UHFFFAOYSA-N lithium;propane Chemical compound [Li+].C[CH-]C SZAVVKVUMPLRRS-UHFFFAOYSA-N 0.000 description 1
- XBEREOHJDYAKDA-UHFFFAOYSA-N lithium;propane Chemical compound [Li+].CC[CH2-] XBEREOHJDYAKDA-UHFFFAOYSA-N 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- QUXHCILOWRXCEO-UHFFFAOYSA-M magnesium;butane;chloride Chemical compound [Mg+2].[Cl-].CCC[CH2-] QUXHCILOWRXCEO-UHFFFAOYSA-M 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- UGVPKMAWLOMPRS-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].CC[CH2-] UGVPKMAWLOMPRS-UHFFFAOYSA-M 0.000 description 1
- 210000001758 mesenteric vein Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- JXEPEXMMOWPOCX-UHFFFAOYSA-N methyl 8-fluoro-5-methyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OC)=C21 JXEPEXMMOWPOCX-UHFFFAOYSA-N 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
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- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000010606 normalization Methods 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
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
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- 238000005192 partition Methods 0.000 description 1
- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
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- YEYSXUKJJMCENU-UHFFFAOYSA-N propan-2-yl 8-fluoro-5-methyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OC(C)C)=C21 YEYSXUKJJMCENU-UHFFFAOYSA-N 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 229940001593 sodium carbonate Drugs 0.000 description 1
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- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- WVMADKBGYOAZKM-UHFFFAOYSA-M sodium;3-aminothiophene-2-carboxylate Chemical compound [Na+].NC=1C=CSC=1C([O-])=O WVMADKBGYOAZKM-UHFFFAOYSA-M 0.000 description 1
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- 238000002560 therapeutic procedure Methods 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/24—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in positions 2 and 4
- C07D265/26—Two oxygen atoms, e.g. isatoic anhydride
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/42—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms with nitro or nitroso radicals directly attached to ring carbon atoms
-
- 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
- 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
- C07D487/12—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 three hetero rings
- C07D487/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Toxicology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH897179 | 1979-10-04 | ||
| CH897279 | 1979-10-04 | ||
| CH1066479 | 1979-11-30 | ||
| CH1066579 | 1979-11-30 | ||
| CH571680 | 1980-07-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ195071A true NZ195071A (en) | 1984-08-24 |
Family
ID=27509256
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ195071A NZ195071A (en) | 1979-10-04 | 1980-09-26 | Imidazo(1,4)diazepines |
Country Status (23)
| Country | Link |
|---|---|
| US (10) | US4316839A (enExample) |
| EP (1) | EP0027214B1 (enExample) |
| JP (1) | JPH01156968A (enExample) |
| AR (1) | AR227293A1 (enExample) |
| AU (1) | AU533641B2 (enExample) |
| BR (1) | BR8006404A (enExample) |
| CA (1) | CA1143728A (enExample) |
| DE (1) | DE3067868D1 (enExample) |
| DK (1) | DK168094B1 (enExample) |
| FI (1) | FI73683C (enExample) |
| GB (1) | GB2060632B (enExample) |
| GR (1) | GR70772B (enExample) |
| HU (1) | HU182675B (enExample) |
| IE (1) | IE50318B1 (enExample) |
| IL (1) | IL61160A (enExample) |
| LU (1) | LU88298I2 (enExample) |
| MC (1) | MC1355A1 (enExample) |
| NL (1) | NL930056I2 (enExample) |
| NO (1) | NO155774C (enExample) |
| NZ (1) | NZ195071A (enExample) |
| PH (1) | PH16607A (enExample) |
| PT (1) | PT71874B (enExample) |
| ZW (1) | ZW21580A1 (enExample) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1143728A (en) * | 1979-10-04 | 1983-03-29 | Max Gerecke | Imidazodiazepine derivatives |
| CA1174673A (en) * | 1981-02-27 | 1984-09-18 | Walter Hunkeler | Imidazodiazepines |
| US4352817A (en) * | 1981-02-27 | 1982-10-05 | Hoffmann-La Roche Inc. | Imidazo-diazepines and their use |
| CA1184175A (en) * | 1981-02-27 | 1985-03-19 | Walter Hunkeler | Imidazodiazepines |
| CA1185602A (en) * | 1981-02-27 | 1985-04-16 | Emilio Kyburz | Imidazodiazepines |
| CA1173441A (en) * | 1981-02-27 | 1984-08-28 | Hoffmann-La Roche Limited | Imidazodiazepines |
| MC1528A1 (fr) * | 1982-07-21 | 1984-04-13 | Hoffmann La Roche | Imidazobenzodiazepines |
| DK151808C (da) * | 1982-11-16 | 1988-06-20 | Ferrosan As | Analogifremgangsmaade til fremstilling af oxadiazolylimidazo-oe1,4aa-benzodiazepinderivater |
| US4723003A (en) * | 1983-05-18 | 1988-02-02 | Hoechst-Roussel Pharmaceuticals Inc. | Benzopyrrolobenzodiazepines and quinobenzodiazepines |
| IL74070A (en) * | 1984-01-19 | 1988-12-30 | Hoffmann La Roche | Imidazodiazepine derivatives,their manufacture and pharmaceutical compositions containing them |
| AU587802B2 (en) * | 1985-03-08 | 1989-08-31 | Ferrosan A/S | Novel oxadiazolyl imidazobenzodiazepine derivatives and methods of preparing such compounds |
| US4745112A (en) * | 1985-05-17 | 1988-05-17 | A/S Ferrosan | Oxadiazolylimidazobenzodiazepine, compositions, and method III |
| US4622320A (en) * | 1985-05-17 | 1986-11-11 | As Ferrosan | Oxadiazolylimidazobenzodiazepine, compositions, and method |
| DK174086D0 (da) * | 1986-04-16 | 1986-04-16 | Ferrosan As | Nye benzodiazepinderivater samt fremgangsmaade til fremstilling af samme |
| FI880814A7 (fi) * | 1987-03-10 | 1988-09-11 | Hoffmann La Roche | Imidazodiazepin-derivat. |
| GB8720414D0 (en) * | 1987-08-28 | 1987-10-07 | Roussel Lab Ltd | Chemical compounds |
| CA1318668C (en) * | 1988-08-05 | 1993-06-01 | Heinz Carmann | Radioiodine benzodiazepine derivatives |
| US5096695A (en) * | 1988-08-05 | 1992-03-17 | Hoffmann-Laroche Inc. | Radioiodine benzodiazepines as brain imaging agents |
| CA1327572C (en) * | 1988-08-31 | 1994-03-08 | F. Hoffmann-La Roche Ag | Imidazodiazepine derivatives |
| GB8909700D0 (en) * | 1989-04-27 | 1989-06-14 | Roussel Lab Ltd | Chemical compounds |
| CA2015336A1 (en) * | 1989-05-19 | 1990-11-19 | F. Hoffmann-La Roche Ag | Imidazodiazepines for the treatment of neurological symptoms |
| FR2660310B1 (fr) * | 1990-03-27 | 1992-06-05 | Adir | Nouveaux derives de la 4h-pyrrolo[1,2a] thieno[2,3-f] diazepine[1,4], leur procede de preparation et les compositions pharmaceutiques les renfermant. |
| US5276028A (en) * | 1990-06-22 | 1994-01-04 | Nordisk A/S | Imidazoquinoxaline compounds |
| US5371080A (en) * | 1990-06-22 | 1994-12-06 | Novo Nordisk A/S | Imidazoquinazoline compounds and their use |
| TW201311B (enExample) * | 1991-06-17 | 1993-03-01 | Hoffmann La Roche | |
| US5565449A (en) * | 1991-10-18 | 1996-10-15 | Genentech, Inc. | Nonpeptidyl integrin inhibitors having specificity for the GPIIb IIIa receptor |
| US5250679A (en) * | 1991-10-18 | 1993-10-05 | Genentech, Inc. | Nonpeptidyl platelet aggregation inhibitors having specificity for the GPIIb III.sub. receptor |
| US5438035A (en) * | 1994-06-24 | 1995-08-01 | American Cyanamid Company | Methods for controlling undesirable plant species with benzodiazepine compounds |
| TW349100B (en) * | 1994-11-11 | 1999-01-01 | Hoffmann La Roche | Oxazolyl- and thiazolylimidazo-benzo- and thienodiazepines |
| US5670640A (en) * | 1996-02-02 | 1997-09-23 | Hoffmann-La Roche Inc. | Process for the manufacture of imidazodiazepine derivatives |
| GB2328940B (en) * | 1997-09-05 | 1999-12-08 | Dong Kook Pharm Co Ltd | A process for preparing benzodiazepine derivatives |
| PT1691811E (pt) | 2003-12-11 | 2014-10-30 | Sunovion Pharmaceuticals Inc | Combinação de um sedativo e de um modulador de neurotransmissores e métodos para melhorar a qualidade do sono e tratamento da depressão |
| WO2006040038A1 (en) | 2004-10-12 | 2006-04-20 | F.Hoffmann-La Roche Ag | Imidazo [1, 5-a]triazolo[1, 5-d]benzodiazepine derivatives for the treatment of cognitive disorders |
| CN101084220B (zh) | 2004-10-20 | 2010-12-15 | 弗·哈夫曼-拉罗切有限公司 | 卤素取代的苯并二氮杂*衍生物 |
| CA2584259C (en) | 2004-10-20 | 2013-04-02 | F. Hoffmann-La Roche Ag | Imidazo-benzodiazepine derivatives |
| CA2590333C (en) | 2004-12-14 | 2013-01-08 | F. Hoffmann-La Roche Ag | Tetracyclic imidazo-benzodiazepines as gaba receptors modulators |
| AU2006276998A1 (en) * | 2005-05-16 | 2007-02-15 | Wisys Technology Foundation, Inc. | Gabaergic agents to treat memory deficits |
| US7678363B2 (en) | 2005-08-26 | 2010-03-16 | Braincells Inc | Methods of treating psychiatric conditions comprising administration of muscarinic agents in combination with SSRIs |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
| EP1940389A2 (en) | 2005-10-21 | 2008-07-09 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| US20070112017A1 (en) * | 2005-10-31 | 2007-05-17 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20070244143A1 (en) * | 2006-03-08 | 2007-10-18 | Braincells, Inc | Modulation of neurogenesis by nootropic agents |
| US20100216734A1 (en) * | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| EP2382975A3 (en) | 2006-05-09 | 2012-02-29 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| JP2009536667A (ja) * | 2006-05-09 | 2009-10-15 | ブレインセルス，インコーポレイティド | ５ｈｔ受容体介在性の神経新生 |
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| US20090054412A1 (en) * | 2007-08-20 | 2009-02-26 | John Alan Kemp | Treatment of Sleep Disorders |
| WO2009024325A2 (en) | 2007-08-20 | 2009-02-26 | Evotec Neurosciences Gmbh | Treatment of sleep disorders |
| US20090270373A1 (en) * | 2008-04-11 | 2009-10-29 | Cypress Biosciences, Inc. | Treatment of down syndrom with benzodiazepine receptor antagonists |
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Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3933794A (en) * | 1971-08-04 | 1976-01-20 | The Upjohn Company | 2-(2-Alkynylamino)-3H-1,4-benzodiazepines |
| US4031079A (en) * | 1975-09-22 | 1977-06-21 | Mcneil Laboratories, Incorporated | Intermediates for 2-aminobenzodiazepine-5-ones |
| US4002610A (en) * | 1975-09-22 | 1977-01-11 | Mcneil Laboratories, Incorporated | 2-Aminobenzodiazepine-5-ones |
| US4118386A (en) * | 1977-04-04 | 1978-10-03 | Hoffmann-La Roche Inc. | Synthesis of imidazo[1,5-a]diazepine-3-carboxylates |
| ZA806016B (en) * | 1979-10-04 | 1981-09-30 | Hoffmann La Roche | Imidazodiazepine derivatives |
| CA1143728A (en) * | 1979-10-04 | 1983-03-29 | Max Gerecke | Imidazodiazepine derivatives |
| JPH089074B2 (ja) * | 1987-07-02 | 1996-01-31 | 株式会社アマダ | タレツトパンチプレス |
-
1980
- 1980-09-10 CA CA000360028A patent/CA1143728A/en not_active Expired
- 1980-09-15 DK DK391280A patent/DK168094B1/da not_active IP Right Cessation
- 1980-09-19 ZW ZW215/80A patent/ZW21580A1/xx unknown
- 1980-09-26 NZ NZ195071A patent/NZ195071A/en unknown
- 1980-09-29 AU AU62782/80A patent/AU533641B2/en not_active Expired
- 1980-09-29 IL IL61160A patent/IL61160A/xx not_active IP Right Cessation
- 1980-09-30 PH PH24651A patent/PH16607A/en unknown
- 1980-10-01 HU HU802390A patent/HU182675B/hu unknown
- 1980-10-02 MC MC801474A patent/MC1355A1/fr unknown
- 1980-10-02 GR GR63031A patent/GR70772B/el unknown
- 1980-10-02 FI FI803135A patent/FI73683C/fi not_active IP Right Cessation
- 1980-10-02 DE DE8080105970T patent/DE3067868D1/de not_active Expired
- 1980-10-02 EP EP80105970A patent/EP0027214B1/de not_active Expired
- 1980-10-03 NO NO802946A patent/NO155774C/no unknown
- 1980-10-03 AR AR282769A patent/AR227293A1/es active
- 1980-10-03 GB GB8031902A patent/GB2060632B/en not_active Expired
- 1980-10-03 IE IE2056/80A patent/IE50318B1/en not_active IP Right Cessation
- 1980-10-03 US US06/193,775 patent/US4316839A/en not_active Expired - Lifetime
- 1980-10-03 BR BR8006404A patent/BR8006404A/pt unknown
- 1980-10-03 PT PT71874A patent/PT71874B/pt unknown
-
1981
- 1981-11-16 US US06/321,942 patent/US4359420A/en not_active Expired - Lifetime
- 1981-11-16 US US06/322,091 patent/US4363762A/en not_active Expired - Lifetime
- 1981-11-16 US US06/322,113 patent/US4346036A/en not_active Expired - Lifetime
- 1981-11-16 US US06/322,031 patent/US4346035A/en not_active Expired - Lifetime
- 1981-11-16 US US06/321,519 patent/US4346032A/en not_active Expired - Lifetime
- 1981-11-16 US US06/321,491 patent/US4346030A/en not_active Expired - Lifetime
- 1981-11-16 US US06/321,821 patent/US4346033A/en not_active Expired - Lifetime
- 1981-11-16 US US06/321,492 patent/US4346031A/en not_active Expired - Lifetime
- 1981-11-16 US US06/321,941 patent/US4346034A/en not_active Expired - Lifetime
-
1988
- 1988-10-25 JP JP63267347A patent/JPH01156968A/ja active Granted
-
1993
- 1993-06-09 LU LU88298C patent/LU88298I2/fr unknown
- 1993-06-11 NL NL930056C patent/NL930056I2/nl unknown
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