DE2712309A1 - As-triazinobenzodiazepin-1-one, benzodiazepine, verfahren zu ihrer herstellung und diese enthaltende arzneimittel - Google Patents
As-triazinobenzodiazepin-1-one, benzodiazepine, verfahren zu ihrer herstellung und diese enthaltende arzneimittelInfo
- Publication number
- DE2712309A1 DE2712309A1 DE19772712309 DE2712309A DE2712309A1 DE 2712309 A1 DE2712309 A1 DE 2712309A1 DE 19772712309 DE19772712309 DE 19772712309 DE 2712309 A DE2712309 A DE 2712309A DE 2712309 A1 DE2712309 A1 DE 2712309A1
- Authority
- DE
- Germany
- Prior art keywords
- benzodiazepine
- radical
- chloro
- formula
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 229940049706 benzodiazepine Drugs 0.000 title claims description 19
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 title claims description 10
- 229940126601 medicinal product Drugs 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title description 2
- -1 alkyl radical Chemical class 0.000 claims description 92
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 84
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 76
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 53
- 150000001875 compounds Chemical class 0.000 claims description 50
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 50
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 42
- 239000000460 chlorine Substances 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- 229910052801 chlorine Inorganic materials 0.000 claims description 28
- 150000003254 radicals Chemical class 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 21
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 17
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 17
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- GWSXDWFXNVOIIC-UHFFFAOYSA-N (7-chloro-5-phenyl-3h-1,4-benzodiazepin-2-yl)hydrazine Chemical compound N=1CC(NN)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 GWSXDWFXNVOIIC-UHFFFAOYSA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 150000001557 benzodiazepines Chemical class 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 10
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- VTGZNHLCFHSBQH-UHFFFAOYSA-N [7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]hydrazine Chemical compound N=1CC(NN)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl VTGZNHLCFHSBQH-UHFFFAOYSA-N 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- YAHSPMJGSHKIQY-UHFFFAOYSA-N [5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]hydrazine Chemical compound N=1CC(NN)=NC2=CC=CC=C2C=1C1=CC=CC=C1Cl YAHSPMJGSHKIQY-UHFFFAOYSA-N 0.000 claims description 3
- FIULGFJIHJJXMT-UHFFFAOYSA-N [C]1[N]C=CC=C1 Chemical compound [C]1[N]C=CC=C1 FIULGFJIHJJXMT-UHFFFAOYSA-N 0.000 claims description 3
- BLNWTAHYTCHDJH-UHFFFAOYSA-O hydroxy(oxo)azanium Chemical compound O[NH+]=O BLNWTAHYTCHDJH-UHFFFAOYSA-O 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 2
- 239000004606 Fillers/Extenders Substances 0.000 claims 1
- 241000907681 Morpho Species 0.000 claims 1
- 239000012050 conventional carrier Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- 239000000243 solution Substances 0.000 description 86
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 50
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 238000010992 reflux Methods 0.000 description 36
- 238000001704 evaporation Methods 0.000 description 34
- 238000003756 stirring Methods 0.000 description 33
- 230000008020 evaporation Effects 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 229960000583 acetic acid Drugs 0.000 description 28
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- 235000011054 acetic acid Nutrition 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 22
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- ZPFKRQXYKULZKP-UHFFFAOYSA-N butylidene Chemical group [CH2+]CC[CH-] ZPFKRQXYKULZKP-UHFFFAOYSA-N 0.000 description 15
- 238000000921 elemental analysis Methods 0.000 description 14
- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical group [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 description 14
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 14
- 238000002329 infrared spectrum Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000012453 solvate Substances 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 238000000354 decomposition reaction Methods 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 239000007795 chemical reaction product Substances 0.000 description 9
- CWKLZLBVOJRSOM-UHFFFAOYSA-N methyl pyruvate Chemical compound COC(=O)C(C)=O CWKLZLBVOJRSOM-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 5
- RQPJQWJGFPUTJR-UHFFFAOYSA-N 2-[(7-chloro-5-phenyl-3h-1,4-benzodiazepin-2-yl)hydrazinylidene]butanoic acid Chemical compound N=1CC(NN=C(CC)C(O)=O)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 RQPJQWJGFPUTJR-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 230000001914 calming effect Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- BEIABOSLZNBECH-UHFFFAOYSA-N 2-[(7-chloro-5-phenyl-3h-1,4-benzodiazepin-2-yl)hydrazinylidene]-3-hydroxypropanoic acid Chemical compound N=1CC(NN=C(CO)C(O)=O)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 BEIABOSLZNBECH-UHFFFAOYSA-N 0.000 description 3
- ODTIZYMTVFUJGL-UHFFFAOYSA-N 2-[(7-chloro-5-phenyl-3h-1,4-benzodiazepin-2-yl)hydrazinylidene]-5-morpholin-4-ylpentanoic acid Chemical compound N=1C2=CC=C(Cl)C=C2C(C=2C=CC=CC=2)=NCC=1NN=C(C(=O)O)CCCN1CCOCC1 ODTIZYMTVFUJGL-UHFFFAOYSA-N 0.000 description 3
- HRTFTQZLWYRNQF-UHFFFAOYSA-N 2-[(7-chloro-5-phenyl-3h-1,4-benzodiazepin-2-yl)hydrazinylidene]pentanedioic acid Chemical compound N=1CC(NN=C(CCC(=O)O)C(O)=O)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 HRTFTQZLWYRNQF-UHFFFAOYSA-N 0.000 description 3
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- SJXVMLRXFONTJX-UHFFFAOYSA-N 2-[(7-nitro-5-phenyl-3h-1,4-benzodiazepin-2-yl)hydrazinylidene]-5-piperidin-1-ylpentanoic acid Chemical compound N=1C2=CC=C([N+]([O-])=O)C=C2C(C=2C=CC=CC=2)=NCC=1NN=C(C(=O)O)CCCN1CCCCC1 SJXVMLRXFONTJX-UHFFFAOYSA-N 0.000 description 3
- UCNVPUAHONWYBN-UHFFFAOYSA-N 2-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]hydrazinylidene]pent-4-enoic acid Chemical compound N=1CC(NN=C(CC=C)C(=O)O)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl UCNVPUAHONWYBN-UHFFFAOYSA-N 0.000 description 3
- NCGVELQPDRMGDA-UHFFFAOYSA-N 2-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]hydrazinylidene]propanoic acid Chemical compound N=1CC(NN=C(C)C(O)=O)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl NCGVELQPDRMGDA-UHFFFAOYSA-N 0.000 description 3
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- 238000006969 Curtius rearrangement reaction Methods 0.000 description 3
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- 229910052794 bromium Inorganic materials 0.000 description 3
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- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
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- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
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- LYAHDWLIDLPHNF-UHFFFAOYSA-N 2-[(7-chloro-5-phenyl-3h-1,4-benzodiazepin-2-yl)hydrazinylidene]-3-pyrrolidin-1-ylpropanoic acid Chemical compound N=1C2=CC=C(Cl)C=C2C(C=2C=CC=CC=2)=NCC=1NN=C(C(=O)O)CN1CCCC1 LYAHDWLIDLPHNF-UHFFFAOYSA-N 0.000 description 2
- YXKLICPOXLKPER-UHFFFAOYSA-N 2-[(7-chloro-5-phenyl-3h-1,4-benzodiazepin-2-yl)hydrazinylidene]acetic acid Chemical compound N=1CC(NN=CC(=O)O)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 YXKLICPOXLKPER-UHFFFAOYSA-N 0.000 description 2
- XJRCMMNPQMQWNL-UHFFFAOYSA-N 2-[[7-bromo-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]hydrazinylidene]-4-methoxybutanoic acid Chemical compound N=1CC(NN=C(CCOC)C(O)=O)=NC2=CC=C(Br)C=C2C=1C1=CC=CC=C1Cl XJRCMMNPQMQWNL-UHFFFAOYSA-N 0.000 description 2
- HYHCKBCAXQPFJD-UHFFFAOYSA-N 2-[[7-chloro-5-(2-chlorophenyl)-3h-1,4-benzodiazepin-2-yl]hydrazinylidene]-3-hydroxypropanoic acid Chemical compound N=1CC(NN=C(CO)C(O)=O)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl HYHCKBCAXQPFJD-UHFFFAOYSA-N 0.000 description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 2
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- FEQAUBVIUZJXKN-UHFFFAOYSA-N propan-2-imine;hydrochloride Chemical compound [Cl-].CC(C)=[NH2+] FEQAUBVIUZJXKN-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IKZWQDXMCQQSLL-UHFFFAOYSA-N propylidenehydrazine Chemical compound CCC=NN IKZWQDXMCQQSLL-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- YVZKICWRYOHMRD-UHFFFAOYSA-N tert-butyl 2-oxopropanoate Chemical compound CC(=O)C(=O)OC(C)(C)C YVZKICWRYOHMRD-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/20—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- 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)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/672,995 US4017492A (en) | 1976-04-02 | 1976-04-02 | As-triazinobenzodiazepin-1-ones |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2712309A1 true DE2712309A1 (de) | 1977-11-17 |
Family
ID=24700887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19772712309 Ceased DE2712309A1 (de) | 1976-04-02 | 1977-03-21 | As-triazinobenzodiazepin-1-one, benzodiazepine, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4017492A (cg-RX-API-DMAC7.html) |
| JP (1) | JPS52122397A (cg-RX-API-DMAC7.html) |
| DE (1) | DE2712309A1 (cg-RX-API-DMAC7.html) |
| FR (1) | FR2346354A1 (cg-RX-API-DMAC7.html) |
| GB (2) | GB1522922A (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0001585A1 (de) * | 1977-10-05 | 1979-05-02 | Ciba-Geigy Ag | Piperazino-pyrrolobenzodiazepine, Verfahren zu ihrer Herstellung sowie pharmazeutische Präparate enthaltend diese Verbindungen |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4073784A (en) * | 1977-03-09 | 1978-02-14 | The Upjohn Company | Certain as-triazino 4,3-a! 1,4!benzodiazepine-1,2-dione compounds |
| US4086230A (en) * | 1977-03-09 | 1978-04-25 | The Upjohn Company | 1,5-Dihydro-7-aryl-as-triazine[4,3,-α][1,4]benzodiazepin-1-ols |
| US4073785A (en) * | 1977-03-09 | 1978-02-14 | The Upjohn Company | Certain as-triazino 4,3-a! 1,4!benzodiazepine derivatives |
| HU179158B (en) * | 1979-04-11 | 1982-08-28 | Egyt Gyogyszervegyeszeti Gyar | Process for producing triasolo-benzo-asimetrical-triasine derivatives |
| US4735941A (en) * | 1986-12-23 | 1988-04-05 | Merck & Co., Inc. | 1,4-benzodiazepines with 5- and 6-membered heterocyclic rings, useful as gastrointestinal and CNS agents |
| US5177071A (en) * | 1991-06-17 | 1993-01-05 | Merck & Co., Inc. | 1,4-benzodiazepines with 6-membered heterocyclic rings to treat panic and anxiety disorder |
| US7320739B2 (en) | 2003-01-02 | 2008-01-22 | 3M Innovative Properties Company | Sound absorptive multilayer composite |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2262653A1 (de) * | 1972-01-03 | 1973-07-19 | Upjohn Co | Neue 7-substituierte 3,5-dihydro-astriazino- eckige klammer auf 4,3-a eckige klammer zu eckige klammer auf 1,4 eckige klammer zu benzodiazepine, deren 6-oxyde und verfahren zu ihrer herstellung |
| US3882112A (en) * | 1973-09-19 | 1975-05-06 | Upjohn Co | 7-Phenyl-3-{8 2-(dialkylamino)-alkyl{9 -3,4-dihydroas-triazino{8 4,3-a{9 {8 1,4{9 benzodiazepin-2(1h)-ones |
| US3901881A (en) * | 1972-01-03 | 1975-08-26 | Upjohn Co | 2-thioxo-1h-1,4-benzodiazepine-1-acetic acid alkyl esters |
| US3933816A (en) * | 1974-09-12 | 1976-01-20 | The Upjohn Company | 3-(Substituted aminomethyl)-7-substituted-3,5-dihydro-as-triazino[4,3-a][1,5]benzodiazepines |
-
1976
- 1976-04-02 US US05/672,995 patent/US4017492A/en not_active Expired - Lifetime
-
1977
- 1977-03-08 GB GB9708/77A patent/GB1522922A/en not_active Expired
- 1977-03-08 GB GB10731/78A patent/GB1522923A/en not_active Expired
- 1977-03-21 DE DE19772712309 patent/DE2712309A1/de not_active Ceased
- 1977-04-01 JP JP3747877A patent/JPS52122397A/ja active Pending
- 1977-04-01 FR FR7709945A patent/FR2346354A1/fr active Granted
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2262653A1 (de) * | 1972-01-03 | 1973-07-19 | Upjohn Co | Neue 7-substituierte 3,5-dihydro-astriazino- eckige klammer auf 4,3-a eckige klammer zu eckige klammer auf 1,4 eckige klammer zu benzodiazepine, deren 6-oxyde und verfahren zu ihrer herstellung |
| US3901881A (en) * | 1972-01-03 | 1975-08-26 | Upjohn Co | 2-thioxo-1h-1,4-benzodiazepine-1-acetic acid alkyl esters |
| US3882112A (en) * | 1973-09-19 | 1975-05-06 | Upjohn Co | 7-Phenyl-3-{8 2-(dialkylamino)-alkyl{9 -3,4-dihydroas-triazino{8 4,3-a{9 {8 1,4{9 benzodiazepin-2(1h)-ones |
| US3933816A (en) * | 1974-09-12 | 1976-01-20 | The Upjohn Company | 3-(Substituted aminomethyl)-7-substituted-3,5-dihydro-as-triazino[4,3-a][1,5]benzodiazepines |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0001585A1 (de) * | 1977-10-05 | 1979-05-02 | Ciba-Geigy Ag | Piperazino-pyrrolobenzodiazepine, Verfahren zu ihrer Herstellung sowie pharmazeutische Präparate enthaltend diese Verbindungen |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2346354B1 (cg-RX-API-DMAC7.html) | 1980-02-29 |
| FR2346354A1 (fr) | 1977-10-28 |
| GB1522923A (en) | 1978-08-31 |
| US4017492A (en) | 1977-04-12 |
| JPS52122397A (en) | 1977-10-14 |
| GB1522922A (en) | 1978-08-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8128 | New person/name/address of the agent |
Representative=s name: HENKEL, G., DR.PHIL. FEILER, L., DR.RER.NAT. HAENZ |
|
| 8110 | Request for examination paragraph 44 | ||
| 8131 | Rejection |