NO832633L - Imidazobenzodiazepiner - Google Patents
ImidazobenzodiazepinerInfo
- Publication number
- NO832633L NO832633L NO832633A NO832633A NO832633L NO 832633 L NO832633 L NO 832633L NO 832633 A NO832633 A NO 832633A NO 832633 A NO832633 A NO 832633A NO 832633 L NO832633 L NO 832633L
- Authority
- NO
- Norway
- Prior art keywords
- benzodiazepine
- imidazo
- oxo
- carboxylate
- mmol
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 72
- -1 cyano, nitro, amino Chemical group 0.000 claims abstract description 47
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
- 239000001257 hydrogen Substances 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 17
- 150000002367 halogens Chemical class 0.000 claims abstract description 17
- 239000002253 acid Substances 0.000 claims abstract description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 12
- 125000006410 propenylene group Chemical group 0.000 claims abstract description 8
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 6
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 5
- 229910052799 carbon Inorganic materials 0.000 claims abstract 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 abstract description 5
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 38
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 239000007858 starting material Substances 0.000 claims description 21
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- 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 15
- 125000003277 amino group Chemical group 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- CUZHFFMELKJWLE-JTQLQIEISA-N (s)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9h-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylic acid Chemical compound O=C1C2=C(Cl)C=CC=C2N2C=NC(C(=O)O)=C2[C@@H]2CCCN21 CUZHFFMELKJWLE-JTQLQIEISA-N 0.000 claims description 11
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 229910052740 iodine Inorganic materials 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- CORDBGAXOSVCEX-VIFPVBQESA-N (s)-8-chloro-12,12a-dihydro-9-oxo-9h,11h-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylic acid Chemical compound O=C1C2=C(Cl)C=CC=C2N2C=NC(C(=O)O)=C2[C@@H]2CCN21 CORDBGAXOSVCEX-VIFPVBQESA-N 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000005809 transesterification reaction Methods 0.000 claims description 4
- CFMIOXCGQIHWJP-UHFFFAOYSA-N 1,2-benzodiazepine-1-carboxylic acid Chemical compound OC(=O)N1N=CC=CC2=CC=CC=C12 CFMIOXCGQIHWJP-UHFFFAOYSA-N 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- JGTPOKBXMCOEEA-INIZCTEOSA-N cyclohexyl (7S)-12-oxo-14-(trifluoromethyl)-2,4,11-triazatetracyclo[11.4.0.02,6.07,11]heptadeca-1(17),3,5,13,15-pentaene-5-carboxylate Chemical compound C1([C@@H]2CCCN2C(=O)C2=C(N1C=N1)C=CC=C2C(F)(F)F)=C1C(=O)OC1CCCCC1 JGTPOKBXMCOEEA-INIZCTEOSA-N 0.000 claims description 3
- WQDACHQRZIFCIW-HNNXBMFYSA-N cyclohexyl (s)-8-chloro-7-fluoro-11,12,13,13a-tetrahydro-9-oxo-9h-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate Chemical compound C1([C@@H]2CCCN2C(=O)C=2C(N1C=N1)=CC=C(C=2Cl)F)=C1C(=O)OC1CCCCC1 WQDACHQRZIFCIW-HNNXBMFYSA-N 0.000 claims description 3
- PRLPLCWIRHDLEM-HNNXBMFYSA-N cyclopropylmethyl (7S)-15-fluoro-12-oxo-2,4,11-triazatetracyclo[11.4.0.02,6.07,11]heptadeca-1(17),3,5,13,15-pentaene-5-carboxylate Chemical compound C1([C@@H]2CCCN2C(=O)C=2C(N1C=N1)=CC=C(C=2)F)=C1C(=O)OCC1CC1 PRLPLCWIRHDLEM-HNNXBMFYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 2
- NWEPUIDYXXNYST-HNNXBMFYSA-N cyclohexyl (7S)-13-chloro-11-oxo-2,4,10-triazatetracyclo[10.4.0.02,6.07,10]hexadeca-1(16),3,5,12,14-pentaene-5-carboxylate Chemical compound C1([C@@H]2CCN2C(=O)C2=C(N1C=N1)C=CC=C2Cl)=C1C(=O)OC1CCCCC1 NWEPUIDYXXNYST-HNNXBMFYSA-N 0.000 claims description 2
- GNUVEUDRTNJIHH-HNNXBMFYSA-N cyclohexyl (s)-12,12a-dihydro-8-iodo-9-oxo-9h,11h-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylate Chemical compound C1([C@@H]2CCN2C(=O)C2=C(N1C=N1)C=CC=C2I)=C1C(=O)OC1CCCCC1 GNUVEUDRTNJIHH-HNNXBMFYSA-N 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 19
- 102000004300 GABA-A Receptors Human genes 0.000 abstract description 9
- 108090000839 GABA-A Receptors Proteins 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 7
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 6
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 abstract description 4
- 239000013543 active substance Substances 0.000 abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 4
- 206010010904 Convulsion Diseases 0.000 abstract description 3
- 230000036461 convulsion Effects 0.000 abstract description 3
- 208000019901 Anxiety disease Diseases 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 230000036961 partial effect Effects 0.000 abstract description 2
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 abstract 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 231100000053 low toxicity Toxicity 0.000 abstract 1
- 230000002936 tranquilizing effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 317
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 176
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 160
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 147
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 126
- 239000000243 solution Substances 0.000 description 126
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 108
- 238000002844 melting Methods 0.000 description 107
- 230000008018 melting Effects 0.000 description 107
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 106
- 235000019439 ethyl acetate Nutrition 0.000 description 105
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 91
- 239000000203 mixture Substances 0.000 description 88
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 80
- 235000019341 magnesium sulphate Nutrition 0.000 description 80
- 239000000741 silica gel Substances 0.000 description 67
- 229910002027 silica gel Inorganic materials 0.000 description 67
- 238000001953 recrystallisation Methods 0.000 description 56
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
- 238000003756 stirring Methods 0.000 description 52
- 229960000583 acetic acid Drugs 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
- XGZNHFPFJRZBBT-UHFFFAOYSA-N ethanol;titanium Chemical compound [Ti].CCO.CCO.CCO.CCO XGZNHFPFJRZBBT-UHFFFAOYSA-N 0.000 description 39
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium(IV) ethoxide Substances [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 39
- 239000002904 solvent Substances 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- 238000002425 crystallisation Methods 0.000 description 28
- 230000008025 crystallization Effects 0.000 description 28
- 239000012043 crude product Substances 0.000 description 26
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 26
- 239000000284 extract Substances 0.000 description 25
- 239000012074 organic phase Substances 0.000 description 23
- 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 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000005909 Kieselgur Substances 0.000 description 21
- 238000004587 chromatography analysis Methods 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 229910000104 sodium hydride Inorganic materials 0.000 description 18
- 239000012312 sodium hydride Substances 0.000 description 18
- 239000004533 oil dispersion Substances 0.000 description 17
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 16
- 235000011089 carbon dioxide Nutrition 0.000 description 16
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical class [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 13
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 238000009835 boiling Methods 0.000 description 12
- 239000000839 emulsion Substances 0.000 description 12
- 239000012362 glacial acetic acid Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- IQSYKHVFMYGJER-UHFFFAOYSA-N tert-butyl 2-isocyanoacetate Chemical compound CC(C)(C)OC(=O)C[N+]#[C-] IQSYKHVFMYGJER-UHFFFAOYSA-N 0.000 description 11
- IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 10
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 229910052700 potassium Inorganic materials 0.000 description 10
- 239000011591 potassium Substances 0.000 description 10
- SZAWMNAZUPHMRV-ZDUSSCGKSA-N (s)-1-[(8-chloro-11,12,13,13a-tetrahydro-9-oxo-9h-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-1-yl)carbonyl]imidazole Chemical compound C1([C@@H]2CCCN2C(=O)C2=C(N1C=N1)C=CC=C2Cl)=C1C(=O)N1C=CN=C1 SZAWMNAZUPHMRV-ZDUSSCGKSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 238000010171 animal model Methods 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 6
- 229930182821 L-proline Natural products 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000008064 anhydrides Chemical class 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 229960003529 diazepam Drugs 0.000 description 6
- 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 6
- 239000012954 diazonium Substances 0.000 description 6
- 229960002429 proline Drugs 0.000 description 6
- 239000000829 suppository Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- IADUEWIQBXOCDZ-UHFFFAOYSA-N (2S)-azetidine-2-carboxylic acid Natural products OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- JDFHMNHZTKPJLV-INIZCTEOSA-N cyclohexyl (s)-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9h-imidazo[1,5-a]-pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate Chemical compound C1([C@@H]2CCCN2C(=O)C2=C(N1C=N1)C=CC=C2Br)=C1C(=O)OC1CCCCC1 JDFHMNHZTKPJLV-INIZCTEOSA-N 0.000 description 5
- 150000001989 diazonium salts Chemical class 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 239000004540 pour-on Substances 0.000 description 5
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000932 sedative agent Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- ZTKUOTBNYZPDLU-QMMMGPOBSA-N (s)-5-chloro-1,10a-dihydro-azeto[2,1-c][1,4]benzodiazepine-4,10-(2h,9h)-dione Chemical compound N1C(=O)[C@@H]2CCN2C(=O)C2=C1C=CC=C2Cl ZTKUOTBNYZPDLU-QMMMGPOBSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HTSABYAWKQAHBT-UHFFFAOYSA-N 3-methylcyclohexanol Chemical compound CC1CCCC(O)C1 HTSABYAWKQAHBT-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- LWUDDYHYYNNIQI-ZDUSSCGKSA-N bretazenil Chemical compound O=C1C2=C(Br)C=CC=C2N2C=NC(C(=O)OC(C)(C)C)=C2[C@@H]2CCCN21 LWUDDYHYYNNIQI-ZDUSSCGKSA-N 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229940126601 medicinal product Drugs 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 230000001624 sedative effect Effects 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- YXLUHJZFUMXUJE-LBPRGKRZSA-N tert.butyl (s)-12,12a-dihydro-8-iodo-9-oxo-9h,11h-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylate Chemical compound O=C1C2=C(I)C=CC=C2N2C=NC(C(=O)OC(C)(C)C)=C2[C@@H]2CCN21 YXLUHJZFUMXUJE-LBPRGKRZSA-N 0.000 description 4
- SFMKUHZJUHWYFS-VIFPVBQESA-N (6S)-12-fluoro-3,8-diazatricyclo[7.4.0.03,6]trideca-1(9),10,12-triene-2,7-dione Chemical compound N1C(=O)[C@@H]2CCN2C(=O)C2=CC(F)=CC=C21 SFMKUHZJUHWYFS-VIFPVBQESA-N 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012345 traction test Methods 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- 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
-
- 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
- C07D209/32—Oxygen atoms
- C07D209/38—Oxygen atoms in positions 2 and 3, e.g. isatin
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyrrole Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH446082 | 1982-07-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO832633L true NO832633L (no) | 1984-01-23 |
Family
ID=4276529
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO832633A NO832633L (no) | 1982-07-21 | 1983-07-19 | Imidazobenzodiazepiner |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US4489003A (hu) |
| EP (1) | EP0100906B1 (hu) |
| JP (1) | JPS5933286A (hu) |
| KR (1) | KR840005836A (hu) |
| AT (1) | ATE27160T1 (hu) |
| AU (1) | AU560286B2 (hu) |
| BR (1) | BR8303898A (hu) |
| CA (1) | CA1202969A (hu) |
| CS (1) | CS246063B2 (hu) |
| CU (1) | CU21554A3 (hu) |
| DE (1) | DE3371516D1 (hu) |
| DK (1) | DK335083A (hu) |
| ES (4) | ES8500945A1 (hu) |
| FI (1) | FI832654A (hu) |
| GR (1) | GR79322B (hu) |
| HU (1) | HU189719B (hu) |
| IE (1) | IE56121B1 (hu) |
| IL (1) | IL69242A (hu) |
| MC (1) | MC1528A1 (hu) |
| NO (1) | NO832633L (hu) |
| NZ (1) | NZ204912A (hu) |
| PH (1) | PH18980A (hu) |
| PT (1) | PT77063B (hu) |
| ZA (1) | ZA835147B (hu) |
| ZW (1) | ZW14383A1 (hu) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ210850A (en) * | 1984-01-19 | 1988-10-28 | Hoffmann La Roche | Imidazodiazepine derivatives and pharmaceutical compositions |
| CA1259612A (en) * | 1985-02-28 | 1989-09-19 | Emilio Kyburz | Imidazodiazepine derivatives |
| DK174086D0 (da) * | 1986-04-16 | 1986-04-16 | Ferrosan As | Nye benzodiazepinderivater samt fremgangsmaade til fremstilling af samme |
| GB8720414D0 (en) * | 1987-08-28 | 1987-10-07 | 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 |
| IE910939A1 (en) * | 1990-04-13 | 1991-10-23 | Neurosearch As | Use of benzodiazepine compounds |
| US7160880B1 (en) | 1999-05-14 | 2007-01-09 | Cenes Limited | Short-acting benzodiazepines |
| GB9911152D0 (en) * | 1999-05-14 | 1999-07-14 | Glaxo Group Ltd | Short-acting benzodiazepines |
| US7595395B2 (en) * | 2005-05-16 | 2009-09-29 | Wisys Technology Foundation | Gabaergic agents to treat memory deficits |
| KR20090045233A (ko) | 2006-07-10 | 2009-05-07 | 파이온 유케이 리미티드 | 속효형 벤조디아제핀 염 및 이의 중합체 형태 |
| KR101589314B1 (ko) * | 2007-08-20 | 2016-01-28 | 에보텍 인터내셔널 게엠베하 | 수면 장애의 치료 |
| US20090054412A1 (en) * | 2007-08-20 | 2009-02-26 | John Alan Kemp | Treatment of Sleep Disorders |
| EP2450039A1 (en) | 2010-11-08 | 2012-05-09 | PAION UK Ltd. | Dosing regimen for sedation with CNS 7056 (Remimazolam) |
| AR094963A1 (es) | 2013-03-04 | 2015-09-09 | Ono Pharmaceutical Co | Reacción de oxidación excelente en el índice de conversión |
| WO2021113492A1 (en) * | 2019-12-06 | 2021-06-10 | Schrödinger, Inc. | Cyclic compounds and methods of using same |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1143728A (en) * | 1979-10-04 | 1983-03-29 | Max Gerecke | Imidazodiazepine derivatives |
| US4352817A (en) * | 1981-02-27 | 1982-10-05 | Hoffmann-La Roche Inc. | Imidazo-diazepines and their use |
| CA1173441A (en) * | 1981-02-27 | 1984-08-28 | Hoffmann-La Roche Limited | Imidazodiazepines |
| CA1185602A (en) * | 1981-02-27 | 1985-04-16 | Emilio Kyburz | Imidazodiazepines |
| CA1184175A (en) * | 1981-02-27 | 1985-03-19 | Walter Hunkeler | Imidazodiazepines |
-
1983
- 1983-06-19 MC MC@@@@1648A patent/MC1528A1/xx unknown
- 1983-06-24 CA CA000431129A patent/CA1202969A/en not_active Expired
- 1983-06-24 ZW ZW143/83A patent/ZW14383A1/xx unknown
- 1983-07-14 DE DE8383106920T patent/DE3371516D1/de not_active Expired
- 1983-07-14 AT AT83106920T patent/ATE27160T1/de not_active IP Right Cessation
- 1983-07-14 ZA ZA835147A patent/ZA835147B/xx unknown
- 1983-07-14 EP EP83106920A patent/EP0100906B1/de not_active Expired
- 1983-07-14 US US06/513,571 patent/US4489003A/en not_active Expired - Fee Related
- 1983-07-15 AU AU16888/83A patent/AU560286B2/en not_active Ceased
- 1983-07-15 IL IL69242A patent/IL69242A/xx unknown
- 1983-07-15 NZ NZ204912A patent/NZ204912A/en unknown
- 1983-07-18 HU HU832533A patent/HU189719B/hu unknown
- 1983-07-19 NO NO832633A patent/NO832633L/no unknown
- 1983-07-19 CS CS835419A patent/CS246063B2/cs unknown
- 1983-07-19 KR KR1019830003325A patent/KR840005836A/ko not_active Application Discontinuation
- 1983-07-19 GR GR71965A patent/GR79322B/el unknown
- 1983-07-20 PH PH29251A patent/PH18980A/en unknown
- 1983-07-20 IE IE1696/83A patent/IE56121B1/xx unknown
- 1983-07-20 DK DK335083A patent/DK335083A/da not_active Application Discontinuation
- 1983-07-20 BR BR8303898A patent/BR8303898A/pt unknown
- 1983-07-20 ES ES524280A patent/ES8500945A1/es not_active Expired
- 1983-07-20 PT PT77063A patent/PT77063B/pt unknown
- 1983-07-20 JP JP58131150A patent/JPS5933286A/ja active Pending
- 1983-07-21 FI FI832654A patent/FI832654A/fi not_active Application Discontinuation
- 1983-07-21 CU CU8335935A patent/CU21554A3/es unknown
-
1984
- 1984-03-16 ES ES530672A patent/ES530672A0/es active Granted
- 1984-03-16 ES ES530671A patent/ES8505179A1/es not_active Expired
- 1984-03-16 ES ES530673A patent/ES8504805A1/es not_active Expired
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