CS251795B2 - Method of 5h-2,3-benzodiazepine's derivatives preparation - Google Patents

Method of 5h-2,3-benzodiazepine's derivatives preparation Download PDF

Info

Publication number: CS251795B2
Authority: CS; Czechoslovakia
Prior art keywords: formula; benzodiazepine; compound; methyl; acid
Prior art date: 1984-07-27

Application number

CS855526A

Other languages

Czech (cs)

English (en)

Inventor

Tibor Lang

Jenoe Koeroesi

Ferenc Andrasi

Peter Botka

Tamas Hamori

Pal Berszenyi

Katalina Goldschmidt

Gabor Zolyomi

Istvan Elekes

Zsuzsanna Lang

Original Assignee

Egyt Gyogyszervegyeszeti Gyar

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1984-07-27

Filing date

1985-07-26

Publication date

1987-08-13

1985-07-26 Application filed by Egyt Gyogyszervegyeszeti Gyar filed Critical Egyt Gyogyszervegyeszeti Gyar

1987-08-13 Publication of CS251795B2 publication Critical patent/CS251795B2/cs

Links

238000000034 method Methods 0.000 title claims abstract description 19
238000002360 preparation method Methods 0.000 title claims abstract description 11
YVOHCRLDUPTKOH-UHFFFAOYSA-N 5h-2,3-benzodiazepine Chemical class C1C=NN=CC2=CC=CC=C12 YVOHCRLDUPTKOH-UHFFFAOYSA-N 0.000 title claims abstract description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
150000001875 compounds Chemical class 0.000 claims description 34
150000003839 salts Chemical class 0.000 claims description 20
239000002253 acid Substances 0.000 claims description 15
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
239000000203 mixture Substances 0.000 claims description 10
239000003054 catalyst Substances 0.000 claims description 9
230000009467 reduction Effects 0.000 claims description 8
239000002904 solvent Substances 0.000 claims description 8
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 7
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 5
229910052763 palladium Inorganic materials 0.000 claims description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
239000007868 Raney catalyst Substances 0.000 claims description 3
229910000564 Raney nickel Inorganic materials 0.000 claims description 3
238000009835 boiling Methods 0.000 claims description 3
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 3
239000003960 organic solvent Substances 0.000 claims description 3
229910052697 platinum Inorganic materials 0.000 claims description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
239000012458 free base Substances 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
239000008096 xylene Substances 0.000 claims description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 2
125000000217 alkyl group Chemical group 0.000 claims 2
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 claims 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims 1
239000000654 additive Substances 0.000 claims 1
230000000996 additive effect Effects 0.000 claims 1
QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims 1
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
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230000002539 anti-aggressive effect Effects 0.000 abstract description 2
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230000001379 nervous effect Effects 0.000 abstract 1
239000008194 pharmaceutical composition Substances 0.000 abstract 1
230000002557 soporific effect Effects 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
-1 η-propyl Chemical group 0.000 description 14
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
230000000694 effects Effects 0.000 description 11
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
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PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
RUJBDQSFYCKFAA-UHFFFAOYSA-N Tofisopam Chemical compound N=1N=C(C)C(CC)C2=CC(OC)=C(OC)C=C2C=1C1=CC=C(OC)C(OC)=C1 RUJBDQSFYCKFAA-UHFFFAOYSA-N 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
229940049706 benzodiazepine Drugs 0.000 description 3
239000000969 carrier Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000009472 formulation Methods 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
230000000147 hypnotic effect Effects 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
206010021118 Hypotonia Diseases 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
241001026509 Kata Species 0.000 description 2
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 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000013078 crystal Substances 0.000 description 2
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 2
239000008298 dragée Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
239000008101 lactose 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
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
230000036640 muscle relaxation Effects 0.000 description 2
WWQDEXGFYVSTCX-UHFFFAOYSA-N nerisopam Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)=NN=C1C1=CC=C(N)C=C1 WWQDEXGFYVSTCX-UHFFFAOYSA-N 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
239000013558 reference substance Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
230000002269 spontaneous effect Effects 0.000 description 2
239000007858 starting material Substances 0.000 description 2
GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-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
YRFCABRFRKSXAM-UHFFFAOYSA-N 2,5-dihydro-1H-1,2-benzodiazepine Chemical class C1C=CNNC2=CC=CC=C12 YRFCABRFRKSXAM-UHFFFAOYSA-N 0.000 description 1
SXVUJNAJITZLBF-UHFFFAOYSA-N 2-(7,8-dimethoxy-4-methyl-5h-2,3-benzodiazepin-1-yl)-4,5-dimethoxyaniline Chemical compound C1=C(OC)C(OC)=CC(N)=C1C1=NN=C(C)CC2=CC(OC)=C(OC)C=C12 SXVUJNAJITZLBF-UHFFFAOYSA-N 0.000 description 1
ZSDGHWLLLGYAJV-AHEHSYJASA-N 2-[(E)-[(E)-3-[1-(2-nitrophenyl)pyrrol-2-yl]prop-2-enylidene]amino]guanidine Chemical compound NC(N)=N\N=C\C=C\C1=CC=CN1C1=CC=CC=C1[N+]([O-])=O ZSDGHWLLLGYAJV-AHEHSYJASA-N 0.000 description 1
HTKBNADMNIEZSY-UHFFFAOYSA-N 3-(7,8-diethoxy-4-methyl-5h-2,3-benzodiazepin-1-yl)aniline Chemical compound C1=2C=C(OCC)C(OCC)=CC=2CC(C)=NN=C1C1=CC=CC(N)=C1 HTKBNADMNIEZSY-UHFFFAOYSA-N 0.000 description 1
HUQOOLJMTFBLQT-UHFFFAOYSA-N 3-(7,8-dimethoxy-4-methyl-5h-2,3-benzodiazepin-1-yl)aniline Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)=NN=C1C1=CC=CC(N)=C1 HUQOOLJMTFBLQT-UHFFFAOYSA-N 0.000 description 1
RCLQNICOARASSR-SECBINFHSA-N 3-[(2r)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione Chemical compound FC=1C(=O)N(C)C=2N=CN(C[C@@H](O)CO)C(=O)C=2C=1NC1=CC=C(I)C=C1F RCLQNICOARASSR-SECBINFHSA-N 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
HWCICPGWMPOTSU-UHFFFAOYSA-N 4-(7,8-diethoxy-4-methyl-5h-2,3-benzodiazepin-1-yl)aniline Chemical compound C1=2C=C(OCC)C(OCC)=CC=2CC(C)=NN=C1C1=CC=C(N)C=C1 HWCICPGWMPOTSU-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
229920000742 Cotton Polymers 0.000 description 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000001828 Gelatine Substances 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
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
235000019759 Maize starch Nutrition 0.000 description 1
XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
230000003444 anaesthetic effect Effects 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
230000006399 behavior Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
230000001914 calming effect Effects 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical compound [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
239000012043 crude product Substances 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
229960004756 ethanol Drugs 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229960004592 isopropanol Drugs 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
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230000006742 locomotor activity Effects 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
230000000701 neuroleptic effect Effects 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 1
229960001454 nitrazepam Drugs 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
229960000482 pethidine Drugs 0.000 description 1
230000037081 physical activity Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Substances [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 1
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Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/02—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

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Anesthesiology (AREA)
Pain & Pain Management (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CS855526A 1984-07-27 1985-07-26 Method of 5h-2,3-benzodiazepine's derivatives preparation CS251795B2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
HU842882A HU191698B (en)	1984-07-27	1984-07-27	Process for producing new 1-aryl-5h-2beta-benzodiazepines

Publications (1)

Publication Number	Publication Date
CS251795B2 true CS251795B2 (en)	1987-08-13

Family

ID=10961503

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS855526A CS251795B2 (en)	1984-07-27	1985-07-26	Method of 5h-2,3-benzodiazepine's derivatives preparation

Country Status (23)

Country	Link
US (1)	US4614740A (fr)
JP (1)	JPS6143174A (fr)
AT (1)	AT393123B (fr)
BE (1)	BE902953A (fr)
CA (1)	CA1277660C (fr)
CH (1)	CH667090A5 (fr)
CS (1)	CS251795B2 (fr)
DD (1)	DD236527A5 (fr)
DE (1)	DE3527117C2 (fr)
DK (1)	DK158727C (fr)
ES (1)	ES8608494A1 (fr)
FI (1)	FI84821C (fr)
FR (1)	FR2568252B1 (fr)
GB (1)	GB2162184B (fr)
GR (1)	GR851853B (fr)
HU (1)	HU191698B (fr)
IT (1)	IT1187712B (fr)
NL (1)	NL8502141A (fr)
NO (1)	NO162115C (fr)
PH (1)	PH22420A (fr)
PL (1)	PL145089B1 (fr)
PT (1)	PT80870B (fr)
SE (1)	SE465777B (fr)

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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
HU198494B (en) *	1986-08-15	1989-10-30	Gyogyszerkutato Intezet	Process for producing new 3,4-dihydro-5h-2,3-benzodiazepine derivative and acid addition salts thereof, as well as pharmaceutical compositions comprising same
HU207055B (en) *	1990-10-17	1993-03-01	Gyogyszerkutato Intezet	Process for producing new 5h-2,3-benzodiazepine derivative and pharmaceutical compositions comprising same
US5521174A (en) *	1990-12-21	1996-05-28	Gyogyszerkutato Intezet Kv.	N-acyl-2,3-benzodiazepine derivatives and a method of treating spasms of the skeletal musculature therewith
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
US5639751A (en) *	1990-12-21	1997-06-17	Cyogyszerkutato Intezet Kft	N-acyl-2,3-benzodiazepine derivatives for treating acute and chronic neurodegenerative disorders
TR199501071A2 (tr) *	1994-08-31	1996-06-21	Lilly Co Eli	Dihidro-2,3-benzodiazepin türevlerinin üretilmesi icin stereoselektif islem.
US5665878A (en) *	1994-08-31	1997-09-09	Eli Lilly And Company	Stereoselective process for producing dihydro-2,3-benzodiazepine derivatives
DE19604920A1 (de)	1996-02-01	1997-08-07	Schering Ag	Neue 2,3-Benzodiazepinderivate, deren Herstellung und Verwendung als Arzneimittel
US5891871A (en) *	1996-03-21	1999-04-06	Cocensys, Inc.	Substituted 2,3-benzodiazepin-4-ones and the use thereof
UA67749C2 (uk) *	1997-08-12	2004-07-15	Егіш Дьйодьсердьяр Рт.	Похідна 8-заміщеного-9н-1,3-діоксол/4,5-h//2,3/бензодіазепіну з властивостями амра/каїнатного антагоніста, спосіб одержання похідних, фармацевтична композиція (варіанти), спосіб її одержання та спосіб лікування
HU227128B1 (en) *	1999-07-07	2010-07-28	Egyt Gyogyszervegyeszeti Gyar	New 2,3-benzodiazepine derivatives
EP1296960A2 (fr) *	2000-06-16	2003-04-02	Annovis, Inc.	Antagonistes 5h-2,3-benzodiazepine de recepteurs d'acide amine excitateurs
HU225100B1 (hu) *	2000-12-21	2006-06-28	Egyt Gyogyszervegyeszeti Gyar	2,3-Benzodiazepinszármazékok, ilyen hatóanyagot tartalmazó gyógyászati készítmények és alkalmazásuk
US6649607B2 (en) *	2001-05-18	2003-11-18	Vela Pharmaceuticals, Inc.	Compositions and methods for treating or preventing convulsions or seizures
US7745431B2 (en) *	2002-12-03	2010-06-29	Vela Acquisition Corporation	Pharmaceutical composition of 1-(3,4-dimethoxyphenyl)-4-methyl-5-ethyl-7-methoxy-8-hydroxy-5H-2,3-benzodiazepine and uses thereof
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
MXPA05005893A (es) *	2002-12-03	2006-02-08	Vela Pharmaceuticals Inc	Composicion farmaceutica de 1-(3-hidroxi -4-metoxifenil) -4-metil-5 -etil-7, 8-dimetoxi- 5h-2, 3-benzodiazepina 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
US6858605B2 (en) *	2003-02-04	2005-02-22	Ivax Drug Research Institute, Ltd.	Substituted 2,3-benzodiazepine derivatives
US20040162284A1 (en) *	2003-02-19	2004-08-19	Harris Herbert W.	Method of lowering body temperature with (S) tofisopam
US20040224943A1 (en) *	2003-02-19	2004-11-11	Leventer Steven M.	Method of lowering body temperature with (R) - 2,3-benzodiazepines
US20070021412A1 (en) *	2003-05-16	2007-01-25	Vela Pharmaceuticals, Inc.	Treatment of gastrointestinal dysfunction and related stress with an enantiomerically-pure (S) 2,3-benzodiazepine
WO2004103154A2 (fr) *	2003-05-16	2004-12-02	Vela Pharmaceuticals, Inc.	Traitement d'un dysfonctionnement gastro-intestinal et du stress associe au moyen d'une (r) 2,3-benzodiazepine pure sur le plan enantiomere
US20040254173A1 (en) *	2003-06-13	2004-12-16	Leventer Steven M.	Modulation of dopamine responses with substituted (S)-2,3-benzodiazepines
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
JP4855838B2 (ja) *	2006-02-07	2012-01-18	道夫本郷	錠剤容器
TW200902024A (en) *	2007-04-02	2009-01-16	Teva Pharma	Novel 2,3-benzodiazepine derivatives and their use as antipsychotic agents

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US30014A (en) *		1860-09-11		Bailboad-joint
USRE30014E (en)	1966-12-09	1979-05-29	Egyesult Gyogyazer-es Tapozergyar	1-(3,4-Dimethoxy-phenyl)-4-methyl-5-ethyl-7,8-dimethoxy-5H-2,3-benzodiazepine
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
HU186760B (en) *	1981-03-12	1985-09-30	Gyogyszerkutato Intezet	Process for preparing 3,4-dihydro-5h-2,3-aenzodiazepine derivatives

1984
- 1984-07-27 HU HU842882A patent/HU191698B/hu not_active IP Right Cessation
1985
- 1985-07-11 CH CH3011/85A patent/CH667090A5/de not_active IP Right Cessation
- 1985-07-22 BE BE1/011304A patent/BE902953A/fr not_active IP Right Cessation
- 1985-07-24 ES ES545559A patent/ES8608494A1/es not_active Expired
- 1985-07-25 AT AT2201/85A patent/AT393123B/de not_active IP Right Cessation
- 1985-07-26 PL PL1985254701A patent/PL145089B1/pl unknown
- 1985-07-26 NL NL8502141A patent/NL8502141A/nl not_active Application Discontinuation
- 1985-07-26 CS CS855526A patent/CS251795B2/cs unknown
- 1985-07-26 DK DK340685A patent/DK158727C/da not_active IP Right Cessation
- 1985-07-26 IT IT21725/85A patent/IT1187712B/it active
- 1985-07-26 JP JP60164192A patent/JPS6143174A/ja active Granted
- 1985-07-26 FI FI852906A patent/FI84821C/fi not_active IP Right Cessation
- 1985-07-26 FR FR8511444A patent/FR2568252B1/fr not_active Expired
- 1985-07-26 GB GB08518971A patent/GB2162184B/en not_active Expired
- 1985-07-26 PH PH32569A patent/PH22420A/en unknown
- 1985-07-26 NO NO852973A patent/NO162115C/no unknown
- 1985-07-26 GR GR851853A patent/GR851853B/el unknown
- 1985-07-26 PT PT80870A patent/PT80870B/pt not_active IP Right Cessation
- 1985-07-26 SE SE8503613A patent/SE465777B/sv not_active IP Right Cessation
- 1985-07-26 CA CA000487625A patent/CA1277660C/fr not_active Expired - Lifetime
- 1985-07-26 US US06/759,169 patent/US4614740A/en not_active Expired - Lifetime
- 1985-07-26 DD DD85279022A patent/DD236527A5/de not_active IP Right Cessation
- 1985-07-29 DE DE3527117A patent/DE3527117C2/de not_active Expired - Fee Related

Also Published As

Publication number	Publication date
FR2568252B1 (fr)	1987-03-20
NO852973L (no)	1986-01-28
DD236527A5 (de)	1986-06-11
DE3527117A1 (de)	1986-01-30
CH667090A5 (de)	1988-09-15
DK158727C (da)	1990-12-10
HUT38324A (en)	1986-05-28
PH22420A (en)	1988-09-12
AT393123B (de)	1991-08-26
JPS6143174A (ja)	1986-03-01
SE8503613D0 (sv)	1985-07-26
CA1277660C (fr)	1990-12-11
FI852906L (fi)	1986-01-28
GB2162184B (en)	1987-12-31
PT80870B (pt)	1987-09-18
GB2162184A (en)	1986-01-29
DK340685A (da)	1986-01-28
HU191698B (en)	1987-03-30
JPH0413347B2 (fr)	1992-03-09
DE3527117C2 (de)	1996-08-08
SE465777B (sv)	1991-10-28
IT8521725A0 (it)	1985-07-26
ES545559A0 (es)	1986-07-16
NO162115C (no)	1989-11-08
DK340685D0 (da)	1985-07-26
PL254701A1 (en)	1986-09-09
GB8518971D0 (en)	1985-09-04
GR851853B (fr)	1985-12-02
BE902953A (fr)	1986-01-22
FI84821B (fi)	1991-10-15
NL8502141A (nl)	1986-02-17
FR2568252A1 (fr)	1986-01-31
DK158727B (da)	1990-07-09
FI852906A0 (fi)	1985-07-26
US4614740A (en)	1986-09-30
FI84821C (fi)	1992-01-27
IT1187712B (it)	1987-12-23
PT80870A (en)	1985-08-01
ES8608494A1 (es)	1986-07-16
NO162115B (no)	1989-07-31
PL145089B1 (en)	1988-08-31
SE8503613L (sv)	1986-01-28
ATA220185A (de)	1991-01-15

Publication	Publication Date	Title
CS251795B2 (en)	1987-08-13	Method of 5h-2,3-benzodiazepine's derivatives preparation
RU2102387C1 (ru)	1998-01-20	Производные n-ацил-2,3-бензодиазепина, или их стереоизомеры, или кислые соли присоединения, обладающие биологической активностью, связанной с воздействием на центральную нервную систему, и фармакологически активная композиция на их основе
NZ212856A (en)	1988-05-30	Glutarimide derivatives and pharmaceutical compositions
EP0125607A2 (fr)	1984-11-21	Dérivés de pyrido (1,5) benzodiazépinones à activité pharmacologique
US3317524A (en)	1967-05-02	Substituted 1, 2, 3, 4-tetrahydro-pyrazino[1, 2-a]indoles
US3983239A (en)	1976-09-28	Hexahydro-γ-carboline derivatives and their salts
EP0309544A1 (fr)	1989-04-05	Imides bicycliques psychotropes.
US5204343A (en)	1993-04-20	5h-benzodiazepin derivative
US3711470A (en)	1973-01-16	5-phenyl-7-bromo-1h-1,5-benzodiazepine-2,4-(3h,5h)-diones
CH643263A5 (de)	1984-05-30	Benzodiazepine, ihre herstellung und verwendung.
US3755335A (en)	1973-08-28	CERTAIN 1,2,3,5,6,12,13a-OCTAHYDRO-12-OXO-{8 3,2,1-d,e{9 PYRIDO-{8 1,5{9 -NAPHTHYRIDINES
EP0001585B1 (fr)	1981-07-22	Dérivés de pipérazino-pyrrolobenzodiazépine, leurs procédés de préparation et compositions pharmaceutiques les contenant
USRE28939E (en)	1976-08-24	3-Aminoindazole derivatives
JP2798628B2 (ja)	1998-09-17	癲癇治療用の５−アミノカルボニル−５Ｈ−ジベンゾ［ａ，ｄ］シクロヘプテン−５，１０−イミン
US3941775A (en)	1976-03-02	6-Aza-3H-1,4-benzodiazepines
US3503980A (en)	1970-03-31	Tetrahydroazacycloalkano(1,2-a) pyridazines
EP0118566B1 (fr)	1987-03-04	DERIVES D'INDENO[1,2-b]PYRROLE
US4009271A (en)	1977-02-22	6-aza-3h-1,4-benzodiazepines
US3968230A (en)	1976-07-06	Compositions containing benzodiazepindiones and method of use
US3218326A (en)	1965-11-16	N-aminoalkyl-2, 3-polymethylene-1h-benz[g] indoles and methods of preparing same
US3699098A (en)	1972-10-17	Carboxamides of benzotriazepines
KR100330658B1 (ko)	2002-11-07	1-[2-(치환된비닐)]-5h-2,3-벤조디아제핀유도체
DE69612413T2 (de)	2001-09-27	1-(Hetero)Arylvinyl-5H-2,3-benzodiazepinderivative verwendbar zur Behandlung von Erkrankungen des Zentralnervensystems, sowie Benzopyrylium Intermediate zu ihrer Herstellung
FI74004C (fi)	1987-12-10	Foerfarande foer framstaellning av terapeutiskt anvaendbara piperazinylpyrido/2,3-b/- och -/3,4-b/ pyrazinderivat.
US3972873A (en)	1976-08-03	Certain pyrido[3,2-e]1,4-diazepinones and derivatives