SK281482B6 - 1-[2-(substituovaný vinyl)]-3,4-dihydro-5h-2,3-benzodiazepínové deriváty, spôsob ich prípravy, ich použitie a farmaceutický prostriedok, ktorý ich obsahuje - Google Patents
1-[2-(substituovaný vinyl)]-3,4-dihydro-5h-2,3-benzodiazepínové deriváty, spôsob ich prípravy, ich použitie a farmaceutický prostriedok, ktorý ich obsahuje Download PDFInfo
- Publication number
- SK281482B6 SK281482B6 SK168-96A SK16896A SK281482B6 SK 281482 B6 SK281482 B6 SK 281482B6 SK 16896 A SK16896 A SK 16896A SK 281482 B6 SK281482 B6 SK 281482B6
- Authority
- SK
- Slovakia
- Prior art keywords
- dihydro
- benzodiazepine
- alkyl
- formula
- methyl
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 title abstract description 4
- 229920002554 vinyl polymer Polymers 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- -1 nitro- Chemical group 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 11
- 125000001424 substituent group Chemical group 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 6
- 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 92
- 239000002253 acid Substances 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 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 claims description 8
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 8
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 8
- 230000010933 acylation Effects 0.000 claims description 7
- 238000005917 acylation reaction Methods 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 239000012279 sodium borohydride Substances 0.000 claims description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- YVOHCRLDUPTKOH-UHFFFAOYSA-N 5h-2,3-benzodiazepine Chemical compound C1C=NN=CC2=CC=CC=C12 YVOHCRLDUPTKOH-UHFFFAOYSA-N 0.000 claims description 4
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 4
- 229910000085 borane Inorganic materials 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- LEBLCFHPRYZGJO-UHFFFAOYSA-N n-[4-[2-(3-acetyl-7,8-dimethoxy-4-methyl-4,5-dihydro-2,3-benzodiazepin-1-yl)ethenyl]phenyl]acetamide Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)N(C(C)=O)N=C1C=CC1=CC=C(NC(C)=O)C=C1 LEBLCFHPRYZGJO-UHFFFAOYSA-N 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- VWJHAYXVGFSXJS-UHFFFAOYSA-N 1-[1-[2-(2,3-dimethoxyphenyl)ethenyl]-7,8-dimethoxy-4-methyl-4,5-dihydro-2,3-benzodiazepin-3-yl]ethanone Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)N(C(C)=O)N=C1C=CC1=CC=CC(OC)=C1OC VWJHAYXVGFSXJS-UHFFFAOYSA-N 0.000 claims description 3
- KTMXEEGYNCPVJQ-UHFFFAOYSA-N 7,8-dimethoxy-4-methyl-1-(2-naphthalen-1-ylethenyl)-4,5-dihydro-3h-2,3-benzodiazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)NN=C1C=CC1=CC=CC2=CC=CC=C12 KTMXEEGYNCPVJQ-UHFFFAOYSA-N 0.000 claims description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 3
- 239000007868 Raney catalyst Substances 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- LRJRPHROCLHMHK-UHFFFAOYSA-N boron;n,n-dimethylmethanamine Chemical compound [B].CN(C)C LRJRPHROCLHMHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 229910052987 metal hydride Inorganic materials 0.000 claims description 3
- 150000004681 metal hydrides Chemical class 0.000 claims description 3
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 208000015114 central nervous system disease Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- 229910052763 palladium Inorganic materials 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 abstract description 4
- 210000003169 central nervous system Anatomy 0.000 abstract description 4
- 125000003282 alkyl amino group Chemical group 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 239000012043 crude product Substances 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- LFBZZHVSGAHQPP-UHFFFAOYSA-N GYKI 52466 Chemical compound C12=CC=3OCOC=3C=C2CC(C)=NN=C1C1=CC=C(N)C=C1 LFBZZHVSGAHQPP-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 229950002157 girisopam Drugs 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical class COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 3
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
- RPBDCDQMCRHNLM-UHFFFAOYSA-N C1=NNC=C2C=CC=CC2=C1 Chemical class C1=NNC=C2C=CC=CC2=C1 RPBDCDQMCRHNLM-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 229940025084 amphetamine Drugs 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- GKEVZOBZORFZLH-UHFFFAOYSA-N 1-[1-[2-(2,4-dimethoxyphenyl)ethenyl]-7,8-dimethoxy-4-methyl-4,5-dihydro-2,3-benzodiazepin-3-yl]ethanone Chemical compound COC1=CC(OC)=CC=C1C=CC1=NN(C(C)=O)C(C)CC2=CC(OC)=C(OC)C=C12 GKEVZOBZORFZLH-UHFFFAOYSA-N 0.000 description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
- 125000005808 2,4,6-trimethoxyphenyl group Chemical group [H][#6]-1=[#6](-[#8]C([H])([H])[H])-[#6](-*)=[#6](-[#8]C([H])([H])[H])-[#6]([H])=[#6]-1-[#8]C([H])([H])[H] 0.000 description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 2
- BYKOOYJETDRTMF-UHFFFAOYSA-N 4-[2-(7,8-dimethoxy-4-methyl-4,5-dihydro-3h-2,3-benzodiazepin-1-yl)ethenyl]aniline Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)NN=C1C=CC1=CC=C(N)C=C1 BYKOOYJETDRTMF-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- OJBUZYZQFBEAIE-UHFFFAOYSA-N 7,8-dimethoxy-4-methyl-1-[2-(4-nitrophenyl)ethenyl]-4,5-dihydro-3h-2,3-benzodiazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)NN=C1C=CC1=CC=C([N+]([O-])=O)C=C1 OJBUZYZQFBEAIE-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
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- AHSBXOXPMIOTPJ-UHFFFAOYSA-N NC1=CC2=CC=CC=C2NN=C1C=CC1=CC=CC=C1 Chemical class NC1=CC2=CC=CC=C2NN=C1C=CC1=CC=CC=C1 AHSBXOXPMIOTPJ-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 230000002253 anti-ischaemic effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- VQYLGVVODFDFNK-UHFFFAOYSA-N girisopam Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)=NN=C1C1=CC=CC(Cl)=C1 VQYLGVVODFDFNK-UHFFFAOYSA-N 0.000 description 2
- 230000000971 hippocampal effect Effects 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 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
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
- IYWACWWEVOYCAZ-UHFFFAOYSA-N 1-[2-(1-nitrocyclohexa-2,4-dien-1-yl)ethenyl]-5h-2,3-benzodiazepine Chemical class N=1N=CCC2=CC=CC=C2C=1C=CC1([N+](=O)[O-])CC=CC=C1 IYWACWWEVOYCAZ-UHFFFAOYSA-N 0.000 description 1
- UVDVATXIDNYTRN-UHFFFAOYSA-N 1-[2-(2,4-dimethoxyphenyl)ethenyl]-7,8-dimethoxy-4-methyl-5h-2,3-benzodiazepine Chemical compound COC1=CC(OC)=CC=C1C=CC1=NN=C(C)CC2=CC(OC)=C(OC)C=C12 UVDVATXIDNYTRN-UHFFFAOYSA-N 0.000 description 1
- CQKQBLAVWNVVRW-UHFFFAOYSA-N 1-[5-[2-(2,3-dimethoxyphenyl)ethenyl]-8-methyl-8,9-dihydro-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-7-yl]ethanone Chemical compound COC1=CC=CC(C=CC=2C3=CC=4OCOC=4C=C3CC(C)N(N=2)C(C)=O)=C1OC CQKQBLAVWNVVRW-UHFFFAOYSA-N 0.000 description 1
- FDQQEMCGGDJYLU-UHFFFAOYSA-N 1-[5-[2-(2,4-dimethoxyphenyl)ethenyl]-8-methyl-8,9-dihydro-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-7-yl]ethanone Chemical compound COC1=CC(OC)=CC=C1C=CC(C1=C2)=NN(C(C)=O)C(C)CC1=CC1=C2OCO1 FDQQEMCGGDJYLU-UHFFFAOYSA-N 0.000 description 1
- NIPWMMNTBVBLLN-UHFFFAOYSA-N 1-[5-[2-(4-aminophenyl)ethenyl]-8-methyl-8,9-dihydro-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-7-yl]ethanone Chemical compound N=1N(C(C)=O)C(C)CC2=CC=3OCOC=3C=C2C=1C=CC1=CC=C(N)C=C1 NIPWMMNTBVBLLN-UHFFFAOYSA-N 0.000 description 1
- LWGUFRWEJBHGCD-UHFFFAOYSA-N 1-[5-ethyl-7,8-dimethoxy-4-methyl-1-[2-(4-nitrophenyl)ethenyl]-4,5-dihydro-2,3-benzodiazepin-3-yl]ethanone Chemical compound C12=CC(OC)=C(OC)C=C2C(CC)C(C)N(C(C)=O)N=C1C=CC1=CC=C([N+]([O-])=O)C=C1 LWGUFRWEJBHGCD-UHFFFAOYSA-N 0.000 description 1
- SXXSMYKOUFBFLL-UHFFFAOYSA-N 1-[7,8-dimethoxy-4-methyl-1-(2-phenylethenyl)-4,5-dihydro-2,3-benzodiazepin-3-yl]ethanone Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)N(C(C)=O)N=C1C=CC1=CC=CC=C1 SXXSMYKOUFBFLL-UHFFFAOYSA-N 0.000 description 1
- UEUJRAFFJHADJA-UHFFFAOYSA-N 1-[7,8-dimethoxy-4-methyl-1-[2-(4-nitrophenyl)ethenyl]-4,5-dihydro-2,3-benzodiazepin-3-yl]ethanone Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)N(C(C)=O)N=C1C=CC1=CC=C([N+]([O-])=O)C=C1 UEUJRAFFJHADJA-UHFFFAOYSA-N 0.000 description 1
- HFPAIYLLXACXIA-UHFFFAOYSA-N 1-[8-methyl-5-[2-(4-nitrophenyl)ethenyl]-8,9-dihydro-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-7-yl]ethanone Chemical compound N=1N(C(C)=O)C(C)CC2=CC=3OCOC=3C=C2C=1C=CC1=CC=C([N+]([O-])=O)C=C1 HFPAIYLLXACXIA-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MKWRMWFMOVRTRH-UHFFFAOYSA-N 4,5-dihydro-3h-1,2-benzodiazepine Chemical class C1CCN=NC2=CC=CC=C21 MKWRMWFMOVRTRH-UHFFFAOYSA-N 0.000 description 1
- ZOIDJSXQPWPCDP-UHFFFAOYSA-N 4,5-dihydro-3h-2,3-benzodiazepine Chemical compound C1=NNCCC2=CC=CC=C21 ZOIDJSXQPWPCDP-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
-
- 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
- C07D243/02—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Epidemiology (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 |
|---|---|---|---|
| HU9500386A HU224435B1 (hu) | 1995-02-09 | 1995-02-09 | Benzodiazepin-származékok, eljárás előállításukra, alkalmazásukra és ezeket tartalmazó gyógyászati készítmények |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK16896A3 SK16896A3 (en) | 1996-10-02 |
| SK281482B6 true SK281482B6 (sk) | 2001-04-09 |
Family
ID=10986432
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK168-96A SK281482B6 (sk) | 1995-02-09 | 1996-02-07 | 1-[2-(substituovaný vinyl)]-3,4-dihydro-5h-2,3-benzodiazepínové deriváty, spôsob ich prípravy, ich použitie a farmaceutický prostriedok, ktorý ich obsahuje |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6075018A (cs) |
| JP (1) | JP3354375B2 (cs) |
| KR (1) | KR960031444A (cs) |
| BE (1) | BE1009852A3 (cs) |
| CA (1) | CA2169112A1 (cs) |
| CZ (1) | CZ291218B6 (cs) |
| ES (1) | ES2111492B1 (cs) |
| FI (1) | FI960616A (cs) |
| FR (1) | FR2730490B1 (cs) |
| GB (1) | GB2297749B (cs) |
| HR (1) | HRP960065A2 (cs) |
| HU (1) | HU224435B1 (cs) |
| IT (1) | IT1282591B1 (cs) |
| PL (1) | PL312707A1 (cs) |
| RU (1) | RU2155757C2 (cs) |
| SK (1) | SK281482B6 (cs) |
| UA (1) | UA45954C2 (cs) |
| YU (1) | YU8396A (cs) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6649607B2 (en) | 2001-05-18 | 2003-11-18 | Vela Pharmaceuticals, Inc. | Compositions and methods for treating or preventing convulsions or seizures |
| MXPA05005895A (es) * | 2002-12-03 | 2006-02-08 | Vela Pharmaceuticals Inc | Composicion farmaceutica de 1-(3, 4-dimetoxifenil)-4 -metil-5-etil -7-metoxi-8 -hidroxi- 5h-2, 3-benzodiacepina y usos de la misma. |
| CA2510275A1 (en) * | 2002-12-03 | 2004-08-19 | Vela Pharmaceuticals, Inc. | Pharmaceutical composition of 1-(3-hydroxy-4-methoxyphenyl)-4-methyl-5-ethyl-7,8-dimethoxy-5h-2,3-benzodiazepine and uses therof |
| US6864251B2 (en) * | 2002-12-03 | 2005-03-08 | Vela Pharmaceuticals, Inc. | Treatment of LTB4-mediated inflammatory disorders with optically-pure (R)-2,3-benzodiazepines |
| US6638928B1 (en) | 2002-12-03 | 2003-10-28 | Vela Pharmaceuticals, Inc. | Treatment of irritable bowel syndrome and nonulcer dyspepsia with substituted 2,3-benzodiazepines |
| US7022700B2 (en) * | 2002-12-03 | 2006-04-04 | Vela Pharmaceuticals, Inc. | Method of increasing neutrophil production using optically-pure (R)-2,3-benzodiazepines |
| US20040152694A1 (en) * | 2003-02-04 | 2004-08-05 | Istvan Kurucz | Methods and compositions for treating inflammatory disorders of the airways |
| US20040224943A1 (en) * | 2003-02-19 | 2004-11-11 | Leventer Steven M. | Method of lowering body temperature with (R) - 2,3-benzodiazepines |
| PL1833815T3 (pl) * | 2004-12-30 | 2011-03-31 | Inst Farmaceutyczny | Sposób wytwarzania zasady imatinibu |
| EP2338492A1 (en) | 2009-12-24 | 2011-06-29 | Universidad del Pais Vasco | Methods and compositions for the treatment of alzheimer |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE761315A (cs) * | 1970-01-12 | 1971-07-07 | S M B Anciens Etablissements J | |
| HU179018B (en) * | 1978-10-19 | 1982-08-28 | Gyogyszerkutato Intezet | Process for producing new 5h-2,3-benzodiazepine derivatives |
| HU186760B (en) * | 1981-03-12 | 1985-09-30 | Gyogyszerkutato Intezet | Process for preparing 3,4-dihydro-5h-2,3-aenzodiazepine derivatives |
| HU195788B (en) * | 1986-05-21 | 1988-07-28 | Gyogyszerkutato Intezet | Process for producing 1-/hydroxy-stiryl/-5h-2,3-benzobiazepines and pharmaceutical compositions containing them |
-
1995
- 1995-02-09 HU HU9500386A patent/HU224435B1/hu active IP Right Grant
-
1996
- 1996-02-07 SK SK168-96A patent/SK281482B6/sk unknown
- 1996-02-08 PL PL96312707A patent/PL312707A1/xx unknown
- 1996-02-08 RU RU96102418/04A patent/RU2155757C2/ru active
- 1996-02-08 FR FR9601551A patent/FR2730490B1/fr not_active Expired - Fee Related
- 1996-02-08 UA UA96020483A patent/UA45954C2/uk unknown
- 1996-02-08 BE BE9600110A patent/BE1009852A3/fr not_active IP Right Cessation
- 1996-02-08 CZ CZ1996377A patent/CZ291218B6/cs not_active IP Right Cessation
- 1996-02-08 CA CA002169112A patent/CA2169112A1/en not_active Abandoned
- 1996-02-08 ES ES09600303A patent/ES2111492B1/es not_active Expired - Fee Related
- 1996-02-08 HR HRP9500386A patent/HRP960065A2/hr not_active Application Discontinuation
- 1996-02-09 YU YU8396A patent/YU8396A/sh unknown
- 1996-02-09 IT IT96MI000245A patent/IT1282591B1/it active IP Right Grant
- 1996-02-09 KR KR1019960003129A patent/KR960031444A/ko not_active Application Discontinuation
- 1996-02-09 GB GB9602690A patent/GB2297749B/en not_active Expired - Fee Related
- 1996-02-09 FI FI960616A patent/FI960616A/fi unknown
- 1996-02-09 JP JP02396796A patent/JP3354375B2/ja not_active Expired - Fee Related
- 1996-02-09 US US08/599,235 patent/US6075018A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| FR2730490B1 (fr) | 1997-04-18 |
| PL312707A1 (en) | 1996-08-19 |
| UA45954C2 (uk) | 2002-05-15 |
| CA2169112A1 (en) | 1996-08-10 |
| FI960616A0 (fi) | 1996-02-09 |
| HU224435B1 (hu) | 2005-10-28 |
| FR2730490A1 (fr) | 1996-08-14 |
| YU8396A (sh) | 1998-12-23 |
| ES2111492B1 (es) | 1999-07-01 |
| ITMI960245A0 (cs) | 1996-02-09 |
| ITMI960245A1 (it) | 1997-08-09 |
| FI960616A (fi) | 1996-08-10 |
| HRP960065A2 (en) | 1997-12-31 |
| KR960031444A (ko) | 1996-09-17 |
| US6075018A (en) | 2000-06-13 |
| GB9602690D0 (en) | 1996-04-10 |
| GB2297749B (en) | 1998-07-01 |
| ES2111492A1 (es) | 1998-03-01 |
| JP3354375B2 (ja) | 2002-12-09 |
| GB2297749A (en) | 1996-08-14 |
| BE1009852A3 (fr) | 1997-10-07 |
| JPH08283247A (ja) | 1996-10-29 |
| SK16896A3 (en) | 1996-10-02 |
| CZ37796A3 (en) | 1996-08-14 |
| RU2155757C2 (ru) | 2000-09-10 |
| IT1282591B1 (it) | 1998-03-31 |
| CZ291218B6 (cs) | 2003-01-15 |
| HU9500386D0 (en) | 1995-03-28 |
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