CH623588A5 - Process for the preparation of benzodiazepines - Google Patents
Process for the preparation of benzodiazepines Download PDFInfo
- Publication number
- CH623588A5 CH623588A5 CH1215476A CH1215476A CH623588A5 CH 623588 A5 CH623588 A5 CH 623588A5 CH 1215476 A CH1215476 A CH 1215476A CH 1215476 A CH1215476 A CH 1215476A CH 623588 A5 CH623588 A5 CH 623588A5
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- benzodiazepine
- imidazo
- chlorophenyl
- amino
- Prior art date
Links
- 229940049706 benzodiazepine Drugs 0.000 title claims description 51
- 238000000034 method Methods 0.000 title claims description 18
- 150000001557 benzodiazepines Chemical class 0.000 title claims description 17
- 238000002360 preparation method Methods 0.000 title claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 69
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 65
- -1 ethyl radicals Chemical class 0.000 claims description 45
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 42
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 31
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 28
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 22
- 229910052731 fluorine Inorganic materials 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 16
- 239000000460 chlorine Substances 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 239000012279 sodium borohydride Substances 0.000 claims description 15
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 15
- CETGYTZOZAIXBU-UHFFFAOYSA-N 4-aminobut-2-yn-1-ol Chemical compound NCC#CCO CETGYTZOZAIXBU-UHFFFAOYSA-N 0.000 claims description 14
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 14
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims description 13
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- BQPIGGFYSBELGY-UHFFFAOYSA-N mercury(2+) Chemical class [Hg+2] BQPIGGFYSBELGY-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000005265 dialkylamine group Chemical group 0.000 claims description 4
- BLNWTAHYTCHDJH-UHFFFAOYSA-O hydroxy(oxo)azanium Chemical compound O[NH+]=O BLNWTAHYTCHDJH-UHFFFAOYSA-O 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 claims description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 2
- 150000003254 radicals Chemical group 0.000 claims 3
- 239000002168 alkylating agent Substances 0.000 claims 1
- 229940100198 alkylating agent Drugs 0.000 claims 1
- 125000005604 azodicarboxylate group Chemical group 0.000 claims 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 97
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 91
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 29
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 22
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 18
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 12
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000007795 chemical reaction product Substances 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- DOBUSJIVSSJEDA-UHFFFAOYSA-L 1,3-dioxa-2$l^{6}-thia-4-mercuracyclobutane 2,2-dioxide Chemical compound [Hg+2].[O-]S([O-])(=O)=O DOBUSJIVSSJEDA-UHFFFAOYSA-L 0.000 description 6
- PVWZNXRVRUNWHA-UHFFFAOYSA-N 4h-imidazo[1,2-a][1,4]benzodiazepine Chemical compound C1N=CC2=CC=CC=C2N2C=CN=C12 PVWZNXRVRUNWHA-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 229910000372 mercury(II) sulfate Inorganic materials 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- ASCJVOHEMCUERB-UHFFFAOYSA-N 1h-imidazo[1,2-a][1,4]benzodiazepine Chemical compound N1=CC2=CC=CC=C2N2CC=NC2=C1 ASCJVOHEMCUERB-UHFFFAOYSA-N 0.000 description 5
- ADCKEOMMOFWLON-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-8-fluoro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound FC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=C(C=CC=C3)Cl)C1 ADCKEOMMOFWLON-UHFFFAOYSA-N 0.000 description 5
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 241000271566 Aves Species 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
- 239000002026 chloroform extract Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- AORNGSBEWHHBIZ-UHFFFAOYSA-L mercury(2+) sulfuric acid sulfate Chemical compound [Hg++].OS(O)(=O)=O.[O-]S([O-])(=O)=O AORNGSBEWHHBIZ-UHFFFAOYSA-L 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N n-propyl alcohol Natural products CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- CLQVGOREVSXYIG-UHFFFAOYSA-N 2-(8-bromo-6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound BrC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=NC=CC=C3)C1 CLQVGOREVSXYIG-UHFFFAOYSA-N 0.000 description 3
- YANGACXQIPULJP-UHFFFAOYSA-N 2-[2-(8-bromo-6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethyl]isoindole-1,3-dione Chemical compound BrC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=NC=CC=C2)C1 YANGACXQIPULJP-UHFFFAOYSA-N 0.000 description 3
- DFPYAMUTBTVCSJ-UHFFFAOYSA-N 2-[2-(8-fluoro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethyl]isoindole-1,3-dione Chemical compound FC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=CC=CC=C2)C1 DFPYAMUTBTVCSJ-UHFFFAOYSA-N 0.000 description 3
- HQCYINOLJVBROE-UHFFFAOYSA-N 2-[2-[6-(2-chlorophenyl)-8-nitro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethyl]isoindole-1,3-dione Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=C(C=CC=C2)Cl)C1 HQCYINOLJVBROE-UHFFFAOYSA-N 0.000 description 3
- GFXIHZUUEIAWAA-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-8-nitro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-dimethylethanamine Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=NCC=3N2C(=CN=3)CCN(C)C)C2=C(C=CC=C2)Cl)C=1 GFXIHZUUEIAWAA-UHFFFAOYSA-N 0.000 description 3
- ZBSQVLQPJQPNCH-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-8-nitro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=C(C=CC=C3)Cl)C1 ZBSQVLQPJQPNCH-UHFFFAOYSA-N 0.000 description 3
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 125000000068 chlorophenyl group Chemical group 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 2
- 125000004237 1,4-benzodiazepin-2-yl group Chemical group [H]N1C2=C([H])C([H])=C([H])C([H])=C2C([H])=NC([H])=C1* 0.000 description 2
- IBNBDAYJRGIYEC-UHFFFAOYSA-N 2-(4-hydroxybut-2-ynyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CC#CCO)C(=O)C2=C1 IBNBDAYJRGIYEC-UHFFFAOYSA-N 0.000 description 2
- FFHNKDNVNWTFLU-UHFFFAOYSA-N 2-(8-chloro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=CC=CC=C3)C1 FFHNKDNVNWTFLU-UHFFFAOYSA-N 0.000 description 2
- FBCRSKGSYJATQW-UHFFFAOYSA-N 2-(8-chloro-6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)-N,N-dimethylethanamine Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN(C)C)C3=NC=CC=C3)C1 FBCRSKGSYJATQW-UHFFFAOYSA-N 0.000 description 2
- HFJYVPKIKWZKPW-UHFFFAOYSA-N 2-(8-fluoro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)-N,N-dimethylethanamine Chemical compound FC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN(C)C)C3=CC=CC=C3)C1 HFJYVPKIKWZKPW-UHFFFAOYSA-N 0.000 description 2
- AKJSQNSVSSNLGC-UHFFFAOYSA-N 2-(8-nitro-6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=NC=CC=C3)C1 AKJSQNSVSSNLGC-UHFFFAOYSA-N 0.000 description 2
- ZVIJZRNLKXUVGP-UHFFFAOYSA-N 2-[2-(8-chloro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethyl]isoindole-1,3-dione Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=CC=CC=C2)C1 ZVIJZRNLKXUVGP-UHFFFAOYSA-N 0.000 description 2
- KFKBPKFZBUSCPK-UHFFFAOYSA-N 2-[2-(8-nitro-6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethyl]isoindole-1,3-dione Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=NC=CC=C2)C1 KFKBPKFZBUSCPK-UHFFFAOYSA-N 0.000 description 2
- XRVPRXZYYZWWBV-UHFFFAOYSA-N 2-[2-[2-(azidomethyl)-1,3-dioxolan-2-yl]ethyl]isoindole-1,3-dione Chemical compound N(=[N+]=[N-])CC1(OCCO1)CCN1C(C=2C(C1=O)=CC=CC2)=O XRVPRXZYYZWWBV-UHFFFAOYSA-N 0.000 description 2
- HNOXRZNGDVWTLH-UHFFFAOYSA-N 2-[2-[2-(hydroxymethyl)-1,3-dioxolan-2-yl]ethyl]isoindole-1,3-dione Chemical compound OCC1(OCCO1)CCN1C(C=2C(C1=O)=CC=CC2)=O HNOXRZNGDVWTLH-UHFFFAOYSA-N 0.000 description 2
- NPLNRIGSKVUCTE-UHFFFAOYSA-N 2-[2-[6-(2-chlorophenyl)-8-fluoro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethyl]isoindole-1,3-dione Chemical compound FC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=C(C=CC=C2)Cl)C1 NPLNRIGSKVUCTE-UHFFFAOYSA-N 0.000 description 2
- FDZVRKFEAYLMLB-UHFFFAOYSA-N 2-[2-[8-bromo-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethyl]isoindole-1,3-dione Chemical compound BrC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=C(C=CC=C2)Cl)C1 FDZVRKFEAYLMLB-UHFFFAOYSA-N 0.000 description 2
- ZIEDITYIFQEWDC-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-8-nitro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-diethylethanamine Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=NCC=3N2C(=CN=3)CCN(CC)CC)C2=C(C=CC=C2)Cl)C=1 ZIEDITYIFQEWDC-UHFFFAOYSA-N 0.000 description 2
- QZNAGWZAUFKGMW-UHFFFAOYSA-N 2-[8-bromo-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-dimethylethanamine Chemical compound BrC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN(C)C)C3=C(C=CC=C3)Cl)C1 QZNAGWZAUFKGMW-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- MHMLMLAUFWWDLD-UHFFFAOYSA-N 5-(2-chlorophenyl)-7-fluoro-1,3-dihydro-1,4-benzodiazepine-2-thione Chemical compound C12=CC(F)=CC=C2NC(=S)CN=C1C1=CC=CC=C1Cl MHMLMLAUFWWDLD-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- FQVITTWDTRTWGF-UHFFFAOYSA-N N,N-diethyl-2-(8-fluoro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound FC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN(CC)CC)C3=CC=CC=C3)C1 FQVITTWDTRTWGF-UHFFFAOYSA-N 0.000 description 2
- CAGNHDBGYUJHMS-UHFFFAOYSA-N N,N-dimethyl-2-(8-nitro-6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound [N+](=O)([O-])C=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN(C)C)C3=NC=CC=C3)C1 CAGNHDBGYUJHMS-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000005997 bromomethyl group Chemical group 0.000 description 2
- NEEDEQSZOUAJMU-UHFFFAOYSA-N but-2-yn-1-ol Chemical compound CC#CCO NEEDEQSZOUAJMU-UHFFFAOYSA-N 0.000 description 2
- 230000001914 calming effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000003158 myorelaxant agent Substances 0.000 description 2
- NJPPVKZQTLUDBO-UHFFFAOYSA-N novaluron Chemical compound C1=C(Cl)C(OC(F)(F)C(OC(F)(F)F)F)=CC=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F NJPPVKZQTLUDBO-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010183 spectrum analysis Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- GOOCRIHPADOQAS-ZNUXJMJHSA-N (4ar,5as,8ar,13as,15as,15br)-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2h-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinoline-14-one;sulfuric acid Chemical compound OS(O)(=O)=O.O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1.O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 GOOCRIHPADOQAS-ZNUXJMJHSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PDWMEHWITVHYJP-UHFFFAOYSA-N 1-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepine Chemical compound N1=C(C=CC=C1)C1=CN=C2N1C1=C(C=NC2)C=CC=C1 PDWMEHWITVHYJP-UHFFFAOYSA-N 0.000 description 1
- PTPZBCHKQSHXQZ-UHFFFAOYSA-N 2-(4-bromo-3-oxobutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCC(=O)CBr)C(=O)C2=C1 PTPZBCHKQSHXQZ-UHFFFAOYSA-N 0.000 description 1
- GEALDBHOKNVTTM-UHFFFAOYSA-N 2-(6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical class NCCC1=CN=C2N1C1=C(C(=NC2)C2=NC=CC=C2)C=CC=C1 GEALDBHOKNVTTM-UHFFFAOYSA-N 0.000 description 1
- BTISQOLVMWVTSJ-UHFFFAOYSA-N 2-(8-bromo-6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)-N,N-dimethylethanamine Chemical compound BrC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN(C)C)C3=NC=CC=C3)C1 BTISQOLVMWVTSJ-UHFFFAOYSA-N 0.000 description 1
- DFQHWNOVYDJVOT-UHFFFAOYSA-N 2-(8-chloro-6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=NC=CC=C3)C1 DFQHWNOVYDJVOT-UHFFFAOYSA-N 0.000 description 1
- ASBKFALLXXJWKX-UHFFFAOYSA-N 2-(8-fluoro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound FC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=CC=CC=C3)C1 ASBKFALLXXJWKX-UHFFFAOYSA-N 0.000 description 1
- MRYSJOVKZLQCAM-UHFFFAOYSA-N 2-(8-fluoro-6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound FC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=NC=CC=C3)C1 MRYSJOVKZLQCAM-UHFFFAOYSA-N 0.000 description 1
- RUTMREABMZMZLH-UHFFFAOYSA-N 2-(9-bromo-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound BrC1=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=CC=CC=C3)C=C1 RUTMREABMZMZLH-UHFFFAOYSA-N 0.000 description 1
- VNQLIZGZMHUIBQ-UHFFFAOYSA-N 2-(9-fluoro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)-N,N-dimethylethanamine Chemical compound FC1=CC2=C(C(=NCC=3N2C(=CN=3)CCN(C)C)C2=CC=CC=C2)C=C1 VNQLIZGZMHUIBQ-UHFFFAOYSA-N 0.000 description 1
- MFYHAWMPYGBATF-UHFFFAOYSA-N 2-(9-nitro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound [N+](=O)([O-])C1=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=CC=CC=C3)C=C1 MFYHAWMPYGBATF-UHFFFAOYSA-N 0.000 description 1
- WHYXYFAWXNROJR-UHFFFAOYSA-N 2-[10-chloro-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-dimethylethanamine Chemical compound ClC1=CC=CC=2C(=NCC=3N(C=21)C(=CN=3)CCN(C)C)C1=C(C=CC=C1)Cl WHYXYFAWXNROJR-UHFFFAOYSA-N 0.000 description 1
- CNMQNFJMGJYIIE-UHFFFAOYSA-N 2-[10-chloro-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound ClC1=CC=CC=2C(=NCC=3N(C21)C(=CN3)CCN)C3=C(C=CC=C3)Cl CNMQNFJMGJYIIE-UHFFFAOYSA-N 0.000 description 1
- VQDXILCRSSJOSK-UHFFFAOYSA-N 2-[2-(9-bromo-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethyl]isoindole-1,3-dione Chemical compound BrC1=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=CC=CC=C2)C=C1 VQDXILCRSSJOSK-UHFFFAOYSA-N 0.000 description 1
- RYCBNGGAUSXMFG-UHFFFAOYSA-N 2-[2-(9-fluoro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethyl]isoindole-1,3-dione Chemical compound FC1=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=CC=CC=C2)C=C1 RYCBNGGAUSXMFG-UHFFFAOYSA-N 0.000 description 1
- PUAGEWGUZBIDRJ-UHFFFAOYSA-N 2-[2-(9-nitro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethyl]isoindole-1,3-dione Chemical compound [N+](=O)([O-])C1=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=CC=CC=C2)C=C1 PUAGEWGUZBIDRJ-UHFFFAOYSA-N 0.000 description 1
- ALYJZQHFCCYAFQ-UHFFFAOYSA-N 2-[2-[2-(bromomethyl)-1,3-dioxolan-2-yl]ethyl]isoindole-1,3-dione Chemical compound BrCC1(OCCO1)CCN1C(C=2C(C1=O)=CC=CC2)=O ALYJZQHFCCYAFQ-UHFFFAOYSA-N 0.000 description 1
- RPUQIRSNFAOFAU-UHFFFAOYSA-N 2-[2-[6-(2-chlorophenyl)-10-fluoro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethyl]isoindole-1,3-dione Chemical compound FC1=CC=CC=2C(=NCC=3N(C21)C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=C(C=CC=C2)Cl RPUQIRSNFAOFAU-UHFFFAOYSA-N 0.000 description 1
- WEBYMXPETNSTKH-UHFFFAOYSA-N 2-[2-[6-(2-chlorophenyl)-8-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethyl]isoindole-1,3-dione Chemical compound FC(C=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=C(C=CC=C2)Cl)C1)(F)F WEBYMXPETNSTKH-UHFFFAOYSA-N 0.000 description 1
- XGRFTYSVODBHOS-UHFFFAOYSA-N 2-[2-[6-phenyl-9-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethyl]isoindole-1,3-dione Chemical compound FC(C1=CC2=C(C(=NCC=3N2C(=CN3)CCN3C(C=2C(C3=O)=CC=CC2)=O)C2=CC=CC=C2)C=C1)(F)F XGRFTYSVODBHOS-UHFFFAOYSA-N 0.000 description 1
- CCHIXWSDSYYDRK-UHFFFAOYSA-N 2-[2-[7-chloro-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethyl]isoindole-1,3-dione Chemical compound ClC1=CC=CC2=C1C(=NCC=1N2C(=CN1)CCN1C(C=2C(C1=O)=CC=CC2)=O)C2=C(C=CC=C2)Cl CCHIXWSDSYYDRK-UHFFFAOYSA-N 0.000 description 1
- FMVHPFRZHQQPIT-UHFFFAOYSA-N 2-[6-(2,6-difluorophenyl)-10-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound FC(C1=CC=CC=2C(=NCC=3N(C21)C(=CN3)CCN)C3=C(C=CC=C3F)F)(F)F FMVHPFRZHQQPIT-UHFFFAOYSA-N 0.000 description 1
- FHGSXFNYEKNDAP-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-10-fluoro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-diethylethanamine Chemical compound FC1=CC=CC=2C(=NCC=3N(C=21)C(=CN=3)CCN(CC)CC)C1=C(C=CC=C1)Cl FHGSXFNYEKNDAP-UHFFFAOYSA-N 0.000 description 1
- DEVXGYFUSABCMK-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-10-fluoro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound FC1=CC=CC=2C(=NCC=3N(C21)C(=CN3)CCN)C3=C(C=CC=C3)Cl DEVXGYFUSABCMK-UHFFFAOYSA-N 0.000 description 1
- IFAHLJKLSJBYHX-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound NCCC1=CN=C2N1C1=C(C(=NC2)C2=C(C=CC=C2)Cl)C=CC=C1 IFAHLJKLSJBYHX-UHFFFAOYSA-N 0.000 description 1
- CUHOGLCJVMGUKK-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-8-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-diethylethanamine Chemical compound FC(C=1C=CC2=C(C(=NCC=3N2C(=CN=3)CCN(CC)CC)C2=C(C=CC=C2)Cl)C=1)(F)F CUHOGLCJVMGUKK-UHFFFAOYSA-N 0.000 description 1
- IJRDXLOKCUMLBP-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-8-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-dimethylethanamine Chemical compound FC(C=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN(C)C)C3=C(C=CC=C3)Cl)C1)(F)F IJRDXLOKCUMLBP-UHFFFAOYSA-N 0.000 description 1
- JWSMHZFLMDSHEV-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-8-fluoro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-dimethylethanamine Chemical compound FC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN(C)C)C3=C(C=CC=C3)Cl)C1 JWSMHZFLMDSHEV-UHFFFAOYSA-N 0.000 description 1
- GAVPTWJSAQBYQS-UHFFFAOYSA-N 2-[6-phenyl-10-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound FC(C1=CC=CC=2C(=NCC=3N(C21)C(=CN3)CCN)C3=CC=CC=C3)(F)F GAVPTWJSAQBYQS-UHFFFAOYSA-N 0.000 description 1
- GVPWMZCUZRRBIL-UHFFFAOYSA-N 2-[6-phenyl-9-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound FC(C1=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=CC=CC=C3)C=C1)(F)F GVPWMZCUZRRBIL-UHFFFAOYSA-N 0.000 description 1
- IDNRITQYWHPYMR-UHFFFAOYSA-N 2-[7-bromo-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-diethylethanamine Chemical compound BrC1=CC=CC2=C1C(=NCC=1N2C(=CN=1)CCN(CC)CC)C1=C(C=CC=C1)Cl IDNRITQYWHPYMR-UHFFFAOYSA-N 0.000 description 1
- AEHHWXFLKGIKGH-UHFFFAOYSA-N 2-[7-chloro-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-diethylethanamine Chemical compound ClC1=CC=CC2=C1C(=NCC=1N2C(=CN1)CCN(CC)CC)C1=C(C=CC=C1)Cl AEHHWXFLKGIKGH-UHFFFAOYSA-N 0.000 description 1
- SYJGAGNXNJAPMY-UHFFFAOYSA-N 2-[7-chloro-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound ClC1=CC=CC2=C1C(=NCC=1N2C(=CN1)CCN)C1=C(C=CC=C1)Cl SYJGAGNXNJAPMY-UHFFFAOYSA-N 0.000 description 1
- CTOGCBGYRJXSPP-UHFFFAOYSA-N 2-[8-bromo-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound BrC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=C(C=CC=C3)Cl)C1 CTOGCBGYRJXSPP-UHFFFAOYSA-N 0.000 description 1
- NCNGLPPDHCACDW-UHFFFAOYSA-N 2-[8-chloro-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]-N,N-dimethylethanamine Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C(=CN=3)CCN(C)C)C2=C(C=CC=C2)Cl)C=1 NCNGLPPDHCACDW-UHFFFAOYSA-N 0.000 description 1
- OWUCVIULHHPQRO-UHFFFAOYSA-N 2-[8-chloro-6-(2-chlorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound ClC=1C=CC2=C(C(=NCC=3N2C(=CN3)CCN)C3=C(C=CC=C3)Cl)C1 OWUCVIULHHPQRO-UHFFFAOYSA-N 0.000 description 1
- AIBWPBUAKCMKNS-PPHPATTJSA-N 2-hydroxybenzoic acid;3-[(2s)-1-methylpyrrolidin-2-yl]pyridine Chemical compound OC(=O)C1=CC=CC=C1O.CN1CCC[C@H]1C1=CC=CN=C1 AIBWPBUAKCMKNS-PPHPATTJSA-N 0.000 description 1
- IUYIPEJWPJGRGD-UHFFFAOYSA-N 4-[(7-chloro-5-phenyl-3h-1,4-benzodiazepin-2-yl)amino]but-2-yn-1-ol Chemical compound N=1CC(NCC#CCO)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 IUYIPEJWPJGRGD-UHFFFAOYSA-N 0.000 description 1
- RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
- YBONEDOZZPSNOX-UHFFFAOYSA-N 5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepine-2-thione Chemical compound ClC1=CC=CC=C1C1=NCC(=S)NC2=CC=CC=C12 YBONEDOZZPSNOX-UHFFFAOYSA-N 0.000 description 1
- LZANARFQFSEWHV-UHFFFAOYSA-N 5-phenyl-1,3-dihydro-1,4-benzodiazepine-2-thione Chemical compound C12=CC=CC=C2NC(=S)CN=C1C1=CC=CC=C1 LZANARFQFSEWHV-UHFFFAOYSA-N 0.000 description 1
- RZSVSWWTVNDUKC-UHFFFAOYSA-N 6-(2-chlorophenyl)-4h-imidazo[1,2-a][1,4]benzodiazepine Chemical compound ClC1=CC=CC=C1C1=NCC2=NC=CN2C2=CC=CC=C12 RZSVSWWTVNDUKC-UHFFFAOYSA-N 0.000 description 1
- YSSGEZHDTBOTOL-UHFFFAOYSA-N 6-phenyl-4h-imidazo[1,2-a][1,4]benzodiazepine Chemical compound C12=CC=CC=C2N2C=CN=C2CN=C1C1=CC=CC=C1 YSSGEZHDTBOTOL-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LHWMEKKAKMWHST-UHFFFAOYSA-N C1C(=NCC#CCO)NC2=C(C=CC(=C2)Br)C(=N1)C3=CC=CC=C3 Chemical compound C1C(=NCC#CCO)NC2=C(C=CC(=C2)Br)C(=N1)C3=CC=CC=C3 LHWMEKKAKMWHST-UHFFFAOYSA-N 0.000 description 1
- YGWWGUGWNNQGJP-UHFFFAOYSA-N C1C2=NC=C(N2C3=C(C(=CC=C3)Br)C(=N1)C4=CC=CC=C4Cl)CCN5C(=O)C6=CC=CC=C6C5=O Chemical compound C1C2=NC=C(N2C3=C(C(=CC=C3)Br)C(=N1)C4=CC=CC=C4Cl)CCN5C(=O)C6=CC=CC=C6C5=O YGWWGUGWNNQGJP-UHFFFAOYSA-N 0.000 description 1
- FZWRIJZKXHYTBD-UHFFFAOYSA-N C1C2=NC=C(N2C3=C(C=C(C=C3)Br)C(=N1)C4=CC=CC=C4F)CCN5C(=O)C6=CC=CC=C6C5=O Chemical compound C1C2=NC=C(N2C3=C(C=C(C=C3)Br)C(=N1)C4=CC=CC=C4F)CCN5C(=O)C6=CC=CC=C6C5=O FZWRIJZKXHYTBD-UHFFFAOYSA-N 0.000 description 1
- VDVRFLNEOKYZNS-UHFFFAOYSA-N C1C2=NC=C(N2C3=C(C=CC(=C3)Cl)C(=N1)C4=CC=CC=C4F)CCN Chemical compound C1C2=NC=C(N2C3=C(C=CC(=C3)Cl)C(=N1)C4=CC=CC=C4F)CCN VDVRFLNEOKYZNS-UHFFFAOYSA-N 0.000 description 1
- VHXDZVBVOFCOMG-UHFFFAOYSA-N C1C2=NC=C(N2C3=C(C=CC(=C3)Cl)C(=N1)C4=CC=CC=C4F)CCN5C(=O)C6=CC=CC=C6C5=O Chemical compound C1C2=NC=C(N2C3=C(C=CC(=C3)Cl)C(=N1)C4=CC=CC=C4F)CCN5C(=O)C6=CC=CC=C6C5=O VHXDZVBVOFCOMG-UHFFFAOYSA-N 0.000 description 1
- AWSHGVOPOKPVKW-UHFFFAOYSA-N C1C2=NC=C(N2C3=C(C=CC=C3C(F)(F)F)C(=N1)C4=C(C=CC=C4F)F)CCN5C(=O)C6=CC=CC=C6C5=O Chemical compound C1C2=NC=C(N2C3=C(C=CC=C3C(F)(F)F)C(=N1)C4=C(C=CC=C4F)F)CCN5C(=O)C6=CC=CC=C6C5=O AWSHGVOPOKPVKW-UHFFFAOYSA-N 0.000 description 1
- NSXUPJZRBSBAOC-UHFFFAOYSA-N C1C2=NC=C(N2C3=C(C=CC=C3C(F)(F)F)C(=N1)C4=CC=CC=C4F)CCN Chemical compound C1C2=NC=C(N2C3=C(C=CC=C3C(F)(F)F)C(=N1)C4=CC=CC=C4F)CCN NSXUPJZRBSBAOC-UHFFFAOYSA-N 0.000 description 1
- DJKRZEHBCWRZRN-UHFFFAOYSA-N C1C2=NC=C(N2C3=C(C=CC=C3[N+](=O)[O-])C(=N1)C4=C(C=CC=C4F)F)CCN Chemical compound C1C2=NC=C(N2C3=C(C=CC=C3[N+](=O)[O-])C(=N1)C4=C(C=CC=C4F)F)CCN DJKRZEHBCWRZRN-UHFFFAOYSA-N 0.000 description 1
- UIUJVKDDTKVEIG-UHFFFAOYSA-N CCN(CC)CCC1=CN=C2N1C3=C(C=C(C=C3)Br)C(=NC2)C4=CC=CC=C4Cl Chemical compound CCN(CC)CCC1=CN=C2N1C3=C(C=C(C=C3)Br)C(=NC2)C4=CC=CC=C4Cl UIUJVKDDTKVEIG-UHFFFAOYSA-N 0.000 description 1
- FGANZXUVUGOTMI-UHFFFAOYSA-N CCN(CC)CCC1=CN=C2N1C3=C(C=C(C=C3)Br)C(=NC2)C4=CC=CC=C4F Chemical compound CCN(CC)CCC1=CN=C2N1C3=C(C=C(C=C3)Br)C(=NC2)C4=CC=CC=C4F FGANZXUVUGOTMI-UHFFFAOYSA-N 0.000 description 1
- KXGYQYUKBNILMS-UHFFFAOYSA-N CN(C)CCC1=CN=C2N1C3=C(C=CC(=C3)Br)C(=NC2)C4=CC=CC=C4 Chemical compound CN(C)CCC1=CN=C2N1C3=C(C=CC(=C3)Br)C(=NC2)C4=CC=CC=C4 KXGYQYUKBNILMS-UHFFFAOYSA-N 0.000 description 1
- QYAKLQNSICLZQW-UHFFFAOYSA-N CN(C)CCC1=CN=C2N1C3=C(C=CC=C3C(F)(F)F)C(=NC2)C4=C(C=CC=C4F)F Chemical compound CN(C)CCC1=CN=C2N1C3=C(C=CC=C3C(F)(F)F)C(=NC2)C4=C(C=CC=C4F)F QYAKLQNSICLZQW-UHFFFAOYSA-N 0.000 description 1
- SRPKWKHLRVOHFR-UHFFFAOYSA-N CN(C)CCC1=CN=C2N1C3=C(C=CC=C3C(F)(F)F)C(=NC2)C4=CC=CC=C4 Chemical compound CN(C)CCC1=CN=C2N1C3=C(C=CC=C3C(F)(F)F)C(=NC2)C4=CC=CC=C4 SRPKWKHLRVOHFR-UHFFFAOYSA-N 0.000 description 1
- ABXWOPSAYQGTAC-UHFFFAOYSA-N CN(C)CCC1=CN=C2N1C3=C(C=CC=C3F)C(=NC2)C4=CC=CC=C4Cl Chemical compound CN(C)CCC1=CN=C2N1C3=C(C=CC=C3F)C(=NC2)C4=CC=CC=C4Cl ABXWOPSAYQGTAC-UHFFFAOYSA-N 0.000 description 1
- QDAOCGXDURMPBA-UHFFFAOYSA-N CN(C)CCC1=CN=C2N1C3=C(C=CC=C3[N+](=O)[O-])C(=NC2)C4=C(C=CC=C4F)F Chemical compound CN(C)CCC1=CN=C2N1C3=C(C=CC=C3[N+](=O)[O-])C(=NC2)C4=C(C=CC=C4F)F QDAOCGXDURMPBA-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 1
- 244000052363 Cynodon dactylon Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000014066 European mistletoe Nutrition 0.000 description 1
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 description 1
- 235000019733 Fish meal Nutrition 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- RSQCUTZRPLSHPO-UHFFFAOYSA-N N,N-diethyl-2-(9-fluoro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound FC1=CC2=C(C(=NCC=3N2C(=CN=3)CCN(CC)CC)C2=CC=CC=C2)C=C1 RSQCUTZRPLSHPO-UHFFFAOYSA-N 0.000 description 1
- SDNQJAZFGVQJNP-UHFFFAOYSA-N N,N-diethyl-2-[6-(2-fluorophenyl)-10-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound FC(C1=CC=CC=2C(=NCC=3N(C=21)C(=CN=3)CCN(CC)CC)C1=C(C=CC=C1)F)(F)F SDNQJAZFGVQJNP-UHFFFAOYSA-N 0.000 description 1
- GOGFXLWXYDJRFR-UHFFFAOYSA-N N,N-diethyl-2-[6-phenyl-10-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound FC(C1=CC=CC=2C(=NCC=3N(C=21)C(=CN=3)CCN(CC)CC)C1=CC=CC=C1)(F)F GOGFXLWXYDJRFR-UHFFFAOYSA-N 0.000 description 1
- IKCKMQAPNDIZJG-UHFFFAOYSA-N N,N-diethyl-2-[6-phenyl-9-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound FC(C1=CC2=C(C(=NCC=3N2C(=CN=3)CCN(CC)CC)C2=CC=CC=C2)C=C1)(F)F IKCKMQAPNDIZJG-UHFFFAOYSA-N 0.000 description 1
- REXSTCVLRQBBAY-UHFFFAOYSA-N N,N-dimethyl-2-[6-pyridin-2-yl-8-(trifluoromethyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound FC(C=1C=CC2=C(C(=NCC=3N2C(=CN=3)CCN(C)C)C2=NC=CC=C2)C=1)(F)F REXSTCVLRQBBAY-UHFFFAOYSA-N 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- FIQWABNZCMBXPN-UHFFFAOYSA-N N-methyl-2-(6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound CNCCC1=CN=C2N1C1=C(C(=NC2)C2=CC=CC=C2)C=CC=C1 FIQWABNZCMBXPN-UHFFFAOYSA-N 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 244000152640 Rhipsalis cassutha Species 0.000 description 1
- 235000012300 Rhipsalis cassutha Nutrition 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 235000008515 Setaria glauca Nutrition 0.000 description 1
- 235000001155 Setaria leucopila Nutrition 0.000 description 1
- 244000010062 Setaria pumila Species 0.000 description 1
- 240000003461 Setaria viridis Species 0.000 description 1
- 235000002248 Setaria viridis Nutrition 0.000 description 1
- 235000010086 Setaria viridis var. viridis Nutrition 0.000 description 1
- 240000002439 Sorghum halepense Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical class OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 230000000881 depressing effect Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004212 difluorophenyl group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 229910000474 mercury oxide Inorganic materials 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- HTOLGGNSOCNPBR-UHFFFAOYSA-N n,n'-bis(4-nitrophenyl)ethane-1,2-diamine Chemical compound C1=CC([N+](=O)[O-])=CC=C1NCCNC1=CC=C([N+]([O-])=O)C=C1 HTOLGGNSOCNPBR-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 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
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 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
- 125000005544 phthalimido group Chemical group 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 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
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000028527 righting reflex Effects 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 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
- 229960005453 strychnine Drugs 0.000 description 1
- 229960000412 strychnine sulfate Drugs 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing 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
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical class OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/20—Nitrogen 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61785175A | 1975-09-29 | 1975-09-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH623588A5 true CH623588A5 (en) | 1981-06-15 |
Family
ID=24475310
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1215476A CH623588A5 (en) | 1975-09-29 | 1976-09-24 | Process for the preparation of benzodiazepines |
| CH593380A CH623821A5 (en) | 1975-09-29 | 1980-08-05 | Process for the preparation of novel benzodiazepines |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH593380A CH623821A5 (en) | 1975-09-29 | 1980-08-05 | Process for the preparation of novel benzodiazepines |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS5242898A (enrdf_load_stackoverflow) |
| CH (2) | CH623588A5 (enrdf_load_stackoverflow) |
| DE (1) | DE2642150A1 (enrdf_load_stackoverflow) |
| FR (1) | FR2325382A1 (enrdf_load_stackoverflow) |
| GB (2) | GB1492158A (enrdf_load_stackoverflow) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL295083A (enrdf_load_stackoverflow) | 1962-07-10 |
-
1976
- 1976-08-17 GB GB34126/76A patent/GB1492158A/en not_active Expired
- 1976-08-17 GB GB21967/77A patent/GB1492159A/en not_active Expired
- 1976-09-20 DE DE19762642150 patent/DE2642150A1/de not_active Ceased
- 1976-09-24 CH CH1215476A patent/CH623588A5/de not_active IP Right Cessation
- 1976-09-28 FR FR7629127A patent/FR2325382A1/fr active Granted
- 1976-09-28 JP JP51116478A patent/JPS5242898A/ja active Pending
-
1980
- 1980-08-05 CH CH593380A patent/CH623821A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FR2325382A1 (fr) | 1977-04-22 |
| FR2325382B1 (enrdf_load_stackoverflow) | 1978-11-17 |
| CH623821A5 (en) | 1981-06-30 |
| GB1492158A (en) | 1977-11-16 |
| GB1492159A (en) | 1977-11-16 |
| DE2642150A1 (de) | 1977-04-07 |
| JPS5242898A (en) | 1977-04-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0059386B1 (de) | Imidazodiazepine, Zwischenprodukte und Verfahren zu ihrer Herstellung, sowie diese enthaltende Arzneimittel | |
| CH494766A (de) | Verfahren zur Herstellung von Azaspiroalkandionen | |
| EP0031080A1 (de) | 2-Acylaminomethyl-1,4-benzodiazepine und deren Salze sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE2065678A1 (de) | 3-(5-phenyl-3h-1,4-benzodiazepin-2-yl)carbazinsaeurealkylester, deren saeureanlagerungessalze und verfahren zu deren herstellung | |
| CH622019A5 (en) | Process for the preparation of aminotriazolobenzodiazepines | |
| DE2539131C2 (de) | 8-Chlor-1-[(dimethylamino)methyl]-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepinesowie ein Verfahren zu deren Herstellung | |
| DE2810476A1 (de) | Benzodiazepin-derivate, verfahren zu ihrer herstellung und solche derivate enthaltende arzneimittel | |
| DE2237592C2 (de) | 6-(o-Chlorphenyl)-8-chlor-4H-imidazo-[1,2-a] [1,4]-benzodiazepine und Verfahren zu ihrer Herstellung | |
| DE1770778A1 (de) | Benzodiazepin-Derivate | |
| DE3004381A1 (de) | Benzazepin-derivate | |
| DD150602A5 (de) | Verfahren zur herstellung 6-substituierter 11-alkylen-morphantridine | |
| DE2403808A1 (de) | Verfahren zur herstellung von 1- eckige klammer auf amino- oder 1-substituierten aminomethyl eckige klammer zu -6-phenyl4h-s-triazolo eckige klammer auf 4,3-a eckige klammer zu - eckige klammer auf 1,4 eckige klammer zu benzodiazepinen | |
| DD282457A5 (de) | Verfahren zur herstellung neuer heterocyclischer derivate | |
| DE2539114A1 (de) | 7-substituierte 3-(aminomethyl)- 3,5-dihydro-as-triazino eckige klammer auf 4,3-a eckige klammer zu eckige klammer auf 1,4 eckige klammer zu benzodiazepin-2-(1h)-one und ein verfahren zu deren herstellung | |
| DE2242059A1 (de) | 2,4-dihydro-1h-s-triazolo eckige klammer auf 4,3-a eckige klammer zu eckige klammer auf 1,4 eckige klammer zu benzodiazepine und verfahren zu ihrer herstellung | |
| DE2220615A1 (de) | Neue 1-substituierte 6-Phenyl-4H-s-triazolo-[4,3-a][1,4]-benzodiazepine und Verfahren zu deren Herstellung | |
| EP0072029B1 (de) | Triazolobenzazepine, Verfahren und Zwischenprodukte zu deren Herstellung und diese enthaltende Arzneimittel | |
| CH623588A5 (en) | Process for the preparation of benzodiazepines | |
| DE2754112A1 (de) | 1,4-benzodiazepinderivate, ihre salze und diese verbindungen enthaltende arzneipraeparate | |
| DE2709842A1 (de) | Benzodiazepine, verfahren zu ihrer herstellung und diese enthaltende arzneimittel | |
| DE2220694A1 (de) | 1-substituierte 6-Phenyl-4 H-s-triazolo [4,3-a][1,4]-benzodiazepine und Verfahren zur Herstellung desselben | |
| DE2220716A1 (de) | Neue Amido- und Amino-triazolobenzodiazepine und Verfahren zu ihrer Herstellung | |
| DE3124013A1 (de) | 2-acylaminomethyl-1,4-benzodiazepin-verbindungen sowie verfahren und zwischenprodukte zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| CH629808A5 (de) | Verfahren zur herstellung neuer benzodiazepine. | |
| DE1695211A1 (de) | Verfahren zur Herstellung von Benzodiazepin-Derivaten |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |