CS262690B2 - Process for preparing 1-/hydroxystyryl/-5h-2,3-benzodiazepines - Google Patents
Process for preparing 1-/hydroxystyryl/-5h-2,3-benzodiazepines Download PDFInfo
- Publication number
- CS262690B2 CS262690B2 CS873690A CS369087A CS262690B2 CS 262690 B2 CS262690 B2 CS 262690B2 CS 873690 A CS873690 A CS 873690A CS 369087 A CS369087 A CS 369087A CS 262690 B2 CS262690 B2 CS 262690B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- ethanol
- hydroxystyryl
- compounds
- compound
- formula
- Prior art date
Links
- 229940049706 benzodiazepine Drugs 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 21
- 230000008569 process Effects 0.000 claims description 12
- 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 10
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
- 238000012360 testing method Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000000354 decomposition reaction Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 7
- 239000012467 final product Substances 0.000 description 6
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 5
- 229940039009 isoproterenol Drugs 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- -1 4-Hydroxystyryl Chemical group 0.000 description 4
- 241000282326 Felis catus Species 0.000 description 4
- RNLQIBCLLYYYFJ-UHFFFAOYSA-N amrinone Chemical compound N1C(=O)C(N)=CC(C=2C=CN=CC=2)=C1 RNLQIBCLLYYYFJ-UHFFFAOYSA-N 0.000 description 4
- 230000004872 arterial blood pressure Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000009090 positive inotropic effect Effects 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 229960002105 amrinone Drugs 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 206010049816 Muscle tightness Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000003177 cardiotonic effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000000297 inotrophic effect Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BIQMIYWSZZTXEX-UHFFFAOYSA-N 1-(3,4-dihydroxyphenyl)-2-(propan-2-ylamino)ethanone Chemical compound CC(C)NCC(=O)C1=CC=C(O)C(O)=C1 BIQMIYWSZZTXEX-UHFFFAOYSA-N 0.000 description 1
- ZBJGKLFNZOZAFU-UHFFFAOYSA-N 1-(5h-2,3-benzodiazepin-1-yl)-2-phenylethenol Chemical class N=1N=CCC2=CC=CC=C2C=1C(O)=CC1=CC=CC=C1 ZBJGKLFNZOZAFU-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- KWHUWNWCHVQHOW-UHFFFAOYSA-N 2-[2-(7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepin-1-yl)ethenyl]phenol Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)=NN=C1C=CC1=CC=CC=C1O KWHUWNWCHVQHOW-UHFFFAOYSA-N 0.000 description 1
- XAKMDYVRXXDZPL-UHFFFAOYSA-N 2-methoxy-4-[2-(8-methyl-9H-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-5-yl)ethenyl]phenol Chemical compound COC=1C=C(C=CC2=NN=C(CC3=C2C=C2C(=C3)OCO2)C)C=CC=1O XAKMDYVRXXDZPL-UHFFFAOYSA-N 0.000 description 1
- RQKDTQACQPHOQL-UHFFFAOYSA-N 3h-2,3-benzodiazepine Chemical compound C1=NNC=CC2=CC=CC=C21 RQKDTQACQPHOQL-UHFFFAOYSA-N 0.000 description 1
- IROWCYIEJAOFOW-MERQFXBCSA-N 4-[(1r)-1-hydroxy-2-(propan-2-ylamino)ethyl]benzene-1,2-diol;hydrochloride Chemical compound Cl.CC(C)NC[C@H](O)C1=CC=C(O)C(O)=C1 IROWCYIEJAOFOW-MERQFXBCSA-N 0.000 description 1
- VEECQLAJPUZKLB-UHFFFAOYSA-N 4-[2-(7,8-diethoxy-4-methyl-5H-2,3-benzodiazepin-1-yl)ethenyl]-2-methoxyphenol Chemical compound C1=2C=C(OCC)C(OCC)=CC=2CC(C)=NN=C1C=CC1=CC=C(O)C(OC)=C1 VEECQLAJPUZKLB-UHFFFAOYSA-N 0.000 description 1
- PQNSOSHKHDOPAF-UHFFFAOYSA-N 4-[2-(7,8-diethoxy-4-methyl-5H-2,3-benzodiazepin-1-yl)ethenyl]phenol Chemical compound C1=2C=C(OCC)C(OCC)=CC=2CC(C)=NN=C1C=CC1=CC=C(O)C=C1 PQNSOSHKHDOPAF-UHFFFAOYSA-N 0.000 description 1
- IVCMTOXWDGAHTR-UHFFFAOYSA-N 4-[2-(7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepin-1-yl)ethenyl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC(C=CC=2C3=CC(OC)=C(OC)C=C3CC(C)=NN=2)=C1 IVCMTOXWDGAHTR-UHFFFAOYSA-N 0.000 description 1
- UGTHGDQVFASTSR-UHFFFAOYSA-N 4-[2-(8-methyl-9H-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-5-yl)ethenyl]phenol Chemical compound C12=CC=3OCOC=3C=C2CC(C)=NN=C1C=CC1=CC=C(O)C=C1 UGTHGDQVFASTSR-UHFFFAOYSA-N 0.000 description 1
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
- YVOHCRLDUPTKOH-UHFFFAOYSA-N 5h-2,3-benzodiazepine Chemical class C1C=NN=CC2=CC=CC=C12 YVOHCRLDUPTKOH-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 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
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000496 cardiotonic agent Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000005246 left atrium Anatomy 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 210000003540 papillary muscle Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- NTQLADLBRQMNQJ-UHFFFAOYSA-M pyrylium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.C1=CC=[O+]C=C1 NTQLADLBRQMNQJ-UHFFFAOYSA-M 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU862140A HU195788B (en) | 1986-05-21 | 1986-05-21 | Process for producing 1-/hydroxy-stiryl/-5h-2,3-benzobiazepines and pharmaceutical compositions containing them |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS369087A2 CS369087A2 (en) | 1988-08-16 |
| CS262690B2 true CS262690B2 (en) | 1989-03-14 |
Family
ID=10957976
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS873690A CS262690B2 (en) | 1986-05-21 | 1987-05-21 | Process for preparing 1-/hydroxystyryl/-5h-2,3-benzodiazepines |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US4840948A (enExample) |
| JP (1) | JPS6322082A (enExample) |
| AT (1) | AT395009B (enExample) |
| BE (1) | BE1000573A4 (enExample) |
| BG (1) | BG46003A3 (enExample) |
| CA (1) | CA1280748C (enExample) |
| CH (1) | CH671226A5 (enExample) |
| CS (1) | CS262690B2 (enExample) |
| DD (1) | DD268943A5 (enExample) |
| DE (1) | DE3717080C2 (enExample) |
| DK (1) | DK258187A (enExample) |
| ES (1) | ES2005582A6 (enExample) |
| FI (1) | FI91964C (enExample) |
| FR (1) | FR2599034B1 (enExample) |
| GB (1) | GB2190677B (enExample) |
| HU (1) | HU195788B (enExample) |
| IL (1) | IL82613A (enExample) |
| IT (1) | IT1205665B (enExample) |
| NL (1) | NL8701213A (enExample) |
| PL (1) | PL147687B1 (enExample) |
| PT (1) | PT84923B (enExample) |
| SE (1) | SE468560B (enExample) |
| SU (1) | SU1503681A3 (enExample) |
| YU (1) | YU46675B (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5380721A (en) * | 1990-09-10 | 1995-01-10 | Sterling Winthrop Inc. | Aryl-fused and hetaryl-fused-2,4-diazepine and 2,4-diazocine antiarrhythmic agents |
| HU219778B (hu) * | 1990-12-21 | 2001-07-30 | Gyógyszerkutató Intézet Közös Vállalat | Eljárás N-acil-2,3-benzodiazepin-származékok, savaddíciós sóik és az ezeket tartalmazó gyógyászati készítmények előállítására, valamint a vegyületek egy csoportja, és az ezeket tartalmazó gyógyászati készítmények |
| EP0726257B1 (en) * | 1995-02-09 | 2001-04-11 | Egis Gyogyszergyar Rt. | 1-(Hetero)Arylvinyl-5H-2,3-benzodiazepine derivatives useful for the treatment of central nervous system disorders, and benzopyrylium intermediates for their preparation |
| HU224435B1 (hu) * | 1995-02-09 | 2005-10-28 | EGIS Gyógyszergyár Rt. | Benzodiazepin-származékok, eljárás előállításukra, alkalmazásukra és ezeket tartalmazó gyógyászati készítmények |
| SK283859B6 (sk) * | 1995-02-09 | 2004-03-02 | Egis Gy�Gyszergy�R Rt. | 1-[2'-(Substituovaný)vinyl]-5H-2,3-benzodiazepínové deriváty, spôsob ich prípravy a medziprodukty na ich prípravu, liečivá ich obsahujúce a ich použitie |
| ES2111493B1 (es) * | 1996-02-08 | 1999-08-01 | Egyt Gyogyszervegyeszeti Gyar | Derivados de 1-(2- (vinilo substituido ) ) -5h-2,3-benzo-diazepina, procedimiento para su preparacion, composiciones farmaceuticas que los contienen y utilizaciones correspondientes. |
| HU227128B1 (en) * | 1999-07-07 | 2010-07-28 | Egyt Gyogyszervegyeszeti Gyar | New 2,3-benzodiazepine derivatives |
| 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 |
| US7022700B2 (en) * | 2002-12-03 | 2006-04-04 | Vela Pharmaceuticals, Inc. | Method of increasing neutrophil production using 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 |
| 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. |
| US6864251B2 (en) * | 2002-12-03 | 2005-03-08 | Vela Pharmaceuticals, Inc. | Treatment of LTB4-mediated inflammatory disorders with optically-pure (R)-2,3-benzodiazepines |
| US20040224943A1 (en) * | 2003-02-19 | 2004-11-11 | Leventer Steven M. | Method of lowering body temperature with (R) - 2,3-benzodiazepines |
| US20040162284A1 (en) * | 2003-02-19 | 2004-08-19 | Harris Herbert W. | Method of lowering body temperature with (S) tofisopam |
| HUP0302449A3 (en) * | 2003-08-04 | 2005-06-28 | Egis Gyogyszergyar Nyilvanosan | 8-chloro-2,3-benzodiazepine derivatives, pharmaceutical compositions containing them and process for producing them |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK118660B (da) * | 1966-12-09 | 1970-09-21 | Egyt Gyogyszervegyeszeti Gyar | Analogifremgangsmåde til fremstilling af 1-(3',4'-dimethoxyphenyl)-3-methyl-4-ethyl-6,7-dimethoxy-isoquinolin-N-imid. |
| HU179018B (en) * | 1978-10-19 | 1982-08-28 | Gyogyszerkutato Intezet | Process for producing new 5h-2,3-benzodiazepine derivatives |
| HU191698B (en) * | 1984-07-27 | 1987-03-30 | Gyogyszerkutato Intezet | Process for producing new 1-aryl-5h-2beta-benzodiazepines |
-
1986
- 1986-05-21 HU HU862140A patent/HU195788B/hu not_active IP Right Cessation
-
1987
- 1987-05-19 CH CH1916/87A patent/CH671226A5/de not_active IP Right Cessation
- 1987-05-20 US US07/051,777 patent/US4840948A/en not_active Expired - Fee Related
- 1987-05-21 IT IT20619/87A patent/IT1205665B/it active
- 1987-05-21 BG BG079835A patent/BG46003A3/xx unknown
- 1987-05-21 GB GB8712005A patent/GB2190677B/en not_active Expired - Lifetime
- 1987-05-21 YU YU90687A patent/YU46675B/sh unknown
- 1987-05-21 JP JP62124992A patent/JPS6322082A/ja active Pending
- 1987-05-21 CS CS873690A patent/CS262690B2/cs unknown
- 1987-05-21 SU SU874203194A patent/SU1503681A3/ru active
- 1987-05-21 SE SE8702120A patent/SE468560B/sv not_active IP Right Cessation
- 1987-05-21 FI FI872255A patent/FI91964C/fi not_active IP Right Cessation
- 1987-05-21 BE BE8700571A patent/BE1000573A4/fr not_active IP Right Cessation
- 1987-05-21 CA CA000537655A patent/CA1280748C/en not_active Expired - Lifetime
- 1987-05-21 DK DK258187A patent/DK258187A/da not_active Application Discontinuation
- 1987-05-21 ES ES8701496A patent/ES2005582A6/es not_active Expired
- 1987-05-21 NL NL8701213A patent/NL8701213A/nl not_active Application Discontinuation
- 1987-05-21 PL PL1987265812A patent/PL147687B1/pl unknown
- 1987-05-21 FR FR8707118A patent/FR2599034B1/fr not_active Expired
- 1987-05-21 DD DD87303005A patent/DD268943A5/de not_active IP Right Cessation
- 1987-05-21 IL IL82613A patent/IL82613A/xx unknown
- 1987-05-21 PT PT84923A patent/PT84923B/pt not_active IP Right Cessation
- 1987-05-21 AT AT0130287A patent/AT395009B/de not_active IP Right Cessation
- 1987-05-21 DE DE3717080A patent/DE3717080C2/de not_active Expired - Fee Related
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