DD264431A5 - Verfahren zur herstellung von benzazesin-derivaten - Google Patents

Verfahren zur herstellung von benzazesin-derivaten Download PDF

Info

Publication number: DD264431A5
Authority: DD; German Democratic Republic
Prior art keywords: chloro; benzazecine; hexahydro; dione; acetyl
Prior art date: 1986-01-23

Application number

DD87299380A

Other languages

German (de)

English (en)

Inventor

Werner Aschwanden

Rene Imhof

Roland Jakob

Emilio Kyburz

Original Assignee

�K@��`��@��@�K@��Kk��

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.)

1986-01-23

Filing date

1987-01-21

Publication date

1989-02-01

1987-01-21 Application filed by �K@��`��@��@�K@��Kk�� filed Critical �K@��`��@��@�K@��Kk��

1989-02-01 Publication of DD264431A5 publication Critical patent/DD264431A5/de

Links

238000000034 method Methods 0.000 title claims abstract description 28
230000008569 process Effects 0.000 title claims abstract description 11
238000002360 preparation method Methods 0.000 title claims description 12
-1 chlorobenzoyl Chemical group 0.000 claims abstract description 62
239000001257 hydrogen Substances 0.000 claims abstract description 29
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
239000000460 chlorine Substances 0.000 claims abstract description 24
229910052801 chlorine Inorganic materials 0.000 claims abstract description 20
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 16
150000002431 hydrogen Chemical class 0.000 claims abstract description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 11
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 10
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 8
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 8
229910052794 bromium Inorganic materials 0.000 claims abstract description 8
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 6
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 6
239000011737 fluorine Substances 0.000 claims abstract description 5
229910052731 fluorine Inorganic materials 0.000 claims abstract description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 77
150000001875 compounds Chemical class 0.000 claims description 54
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 31
LOLJNNQHTPVJJR-UHFFFAOYSA-N 1-benzazecine Chemical class N1=CC=CC=CC=CC2=CC=CC=C21 LOLJNNQHTPVJJR-UHFFFAOYSA-N 0.000 claims description 12
230000002490 cerebral effect Effects 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 11
WZJYKHNJTSNBHV-UHFFFAOYSA-N benzo[h]quinoline Chemical class C1=CN=C2C3=CC=CC=C3C=CC2=C1 WZJYKHNJTSNBHV-UHFFFAOYSA-N 0.000 claims description 8
230000003920 cognitive function Effects 0.000 claims description 7
125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 6
230000006872 improvement Effects 0.000 claims description 6
230000002265 prevention Effects 0.000 claims description 6
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 2
230000003647 oxidation Effects 0.000 abstract description 10
238000007254 oxidation reaction Methods 0.000 abstract description 10
239000000825 pharmaceutical preparation Substances 0.000 abstract description 4
BGLCNGRHGALDQI-UHFFFAOYSA-N 1-benzazecine-2,3-dione Chemical class O=C1C(=O)C=CC=CC=C2C=CC=CC2=N1 BGLCNGRHGALDQI-UHFFFAOYSA-N 0.000 abstract 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 174
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 110
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 83
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 78
238000002844 melting Methods 0.000 description 60
230000008018 melting Effects 0.000 description 60
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
239000000243 solution Substances 0.000 description 54
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 35
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 35
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 30
239000012071 phase Substances 0.000 description 30
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
239000011541 reaction mixture Substances 0.000 description 28
238000003756 stirring Methods 0.000 description 27
239000000741 silica gel Substances 0.000 description 26
229910002027 silica gel Inorganic materials 0.000 description 26
239000000725 suspension Substances 0.000 description 26
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
239000000203 mixture Substances 0.000 description 24
238000010992 reflux Methods 0.000 description 22
239000002904 solvent Substances 0.000 description 22
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
229910052757 nitrogen Inorganic materials 0.000 description 19
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 18
229910052943 magnesium sulfate Inorganic materials 0.000 description 17
235000019341 magnesium sulphate Nutrition 0.000 description 17
238000001953 recrystallisation Methods 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
239000013078 crystal Substances 0.000 description 16
239000002245 particle Substances 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 14
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
238000009835 boiling Methods 0.000 description 14
229910052938 sodium sulfate Inorganic materials 0.000 description 14
235000011152 sodium sulphate Nutrition 0.000 description 14
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
238000002425 crystallisation Methods 0.000 description 13
230000008025 crystallization Effects 0.000 description 13
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 10
238000004587 chromatography analysis Methods 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
239000003960 organic solvent Substances 0.000 description 10
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
239000012280 lithium aluminium hydride Substances 0.000 description 9
238000000746 purification Methods 0.000 description 9
241001465754 Metazoa Species 0.000 description 8
239000002026 chloroform extract Substances 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
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 7
OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 7
239000003208 petroleum Substances 0.000 description 7
IHNINSVQYKIZIC-UHFFFAOYSA-N 2h-quinolin-3-one Chemical compound C1=CC=CC2=CC(=O)CN=C21 IHNINSVQYKIZIC-UHFFFAOYSA-N 0.000 description 6
229930000680 A04AD01 - Scopolamine Natural products 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 6
STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
239000012043 crude product Substances 0.000 description 6
238000004042 decolorization Methods 0.000 description 6
238000004519 manufacturing process Methods 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
239000000047 product Substances 0.000 description 6
STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 6
229960002646 scopolamine Drugs 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
239000011734 sodium Substances 0.000 description 6
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 6
235000019345 sodium thiosulphate Nutrition 0.000 description 6
241000700159 Rattus Species 0.000 description 5
239000002253 acid Substances 0.000 description 5
NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 5
239000012153 distilled water Substances 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
230000003285 pharmacodynamic effect Effects 0.000 description 5
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
239000007787 solid Substances 0.000 description 5
238000005406 washing Methods 0.000 description 5
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
229920002261 Corn starch Polymers 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
239000008120 corn starch Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
ZBLPUKDWONQIMX-UHFFFAOYSA-N 8-chloro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=C1C=CC=C2Cl ZBLPUKDWONQIMX-UHFFFAOYSA-N 0.000 description 3
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
239000005977 Ethylene Substances 0.000 description 3
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 3
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
125000002252 acyl group Chemical group 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000002585 base Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000001816 cooling Methods 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000000284 extract Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 3
229910001623 magnesium bromide Inorganic materials 0.000 description 3
239000002808 molecular sieve Substances 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
239000012286 potassium permanganate Substances 0.000 description 3
ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 3
230000009467 reduction Effects 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
230000006403 short-term memory Effects 0.000 description 3
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 3
238000012360 testing method Methods 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
OHXASHBAWOZUNU-UHFFFAOYSA-N 1-(6-bromo-3,4-dihydronaphthalen-2-yl)pyrrolidine Chemical compound C1CC2=CC(Br)=CC=C2C=C1N1CCCC1 OHXASHBAWOZUNU-UHFFFAOYSA-N 0.000 description 2
XFZOWALKXPPPDD-UHFFFAOYSA-N 1-(6-chloro-3,4-dihydronaphthalen-2-yl)pyrrolidine Chemical compound C1CC2=CC(Cl)=CC=C2C=C1N1CCCC1 XFZOWALKXPPPDD-UHFFFAOYSA-N 0.000 description 2
NAOOTRHULOBFCK-UHFFFAOYSA-N 1-(8-chloro-3,4-dihydronaphthalen-2-yl)pyrrolidine Chemical compound C=1C=2C(Cl)=CC=CC=2CCC=1N1CCCC1 NAOOTRHULOBFCK-UHFFFAOYSA-N 0.000 description 2
ZMWGXGJIAJOHJS-UHFFFAOYSA-N 1-(8-methoxy-2,3,5,6-tetrahydro-1h-benzo[f]quinolin-4-yl)ethanone Chemical compound CC(=O)N1CCCC2=C1CCC1=CC(OC)=CC=C12 ZMWGXGJIAJOHJS-UHFFFAOYSA-N 0.000 description 2
RZNHSEZOLFEFGB-UHFFFAOYSA-N 2-methoxybenzoyl chloride Chemical compound COC1=CC=CC=C1C(Cl)=O RZNHSEZOLFEFGB-UHFFFAOYSA-N 0.000 description 2
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 2
IHPRVZKJZGXTBQ-UHFFFAOYSA-N 3-chloropropan-1-amine;hydron;chloride Chemical compound Cl.NCCCCl IHPRVZKJZGXTBQ-UHFFFAOYSA-N 0.000 description 2
RUQIUASLAXJZIE-UHFFFAOYSA-N 3-methoxybenzoyl chloride Chemical compound COC1=CC=CC(C(Cl)=O)=C1 RUQIUASLAXJZIE-UHFFFAOYSA-N 0.000 description 2
AWOCGXZKCTYRCP-UHFFFAOYSA-N 5-chloro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=C1C=CC=C2Cl AWOCGXZKCTYRCP-UHFFFAOYSA-N 0.000 description 2
MKIJLGJYMAVHPA-UHFFFAOYSA-N 6,8-dichloro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=CC(Cl)=CC(Cl)=C21 MKIJLGJYMAVHPA-UHFFFAOYSA-N 0.000 description 2
QQSYTUUAEZUAKL-UHFFFAOYSA-N 6-chloro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=CC(Cl)=CC=C21 QQSYTUUAEZUAKL-UHFFFAOYSA-N 0.000 description 2
QMXOEISLPMFMBQ-UHFFFAOYSA-N 6-fluoro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=CC(F)=CC=C21 QMXOEISLPMFMBQ-UHFFFAOYSA-N 0.000 description 2
JROPOGXVCHJPHT-UHFFFAOYSA-N 8-chloro-1,2-dihydronaphthalene Chemical compound C1=CCCC2=C1C=CC=C2Cl JROPOGXVCHJPHT-UHFFFAOYSA-N 0.000 description 2
208000007848 Alcoholism Diseases 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
208000012239 Developmental disease Diseases 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
208000027530 Meniere disease Diseases 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
201000007930 alcohol dependence Diseases 0.000 description 2
MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
208000026106 cerebrovascular disease Diseases 0.000 description 2
230000006806 disease prevention Effects 0.000 description 2
238000001035 drying Methods 0.000 description 2
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 2
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000003925 fat Substances 0.000 description 2
230000006870 function Effects 0.000 description 2
239000000499 gel Substances 0.000 description 2
230000036541 health Effects 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
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150000008072 azecines Chemical class 0.000 description 1
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AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
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QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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150000007524 organic acids Chemical class 0.000 description 1
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239000007800 oxidant agent Substances 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
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239000003444 phase transfer catalyst Substances 0.000 description 1
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229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
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HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical class O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
- C07D225/02—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
- C07D225/04—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D225/06—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D227/00—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00
- C07D227/02—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D227/06—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D227/08—Oxygen atoms

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Neurosurgery (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Hospice & Palliative Care (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Steroid Compounds (AREA)
Peptides Or Proteins (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

DD87299380A 1986-01-23 1987-01-21 Verfahren zur herstellung von benzazesin-derivaten DD264431A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CH26686		1986-01-23

Publications (1)

Publication Number	Publication Date
DD264431A5 true DD264431A5 (de)	1989-02-01

Family

ID=4183090

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD87299380A DD264431A5 (de)	1986-01-23	1987-01-21	Verfahren zur herstellung von benzazesin-derivaten

Country Status (30)

Country	Link
US (4)	US4732979A (fr)
EP (1)	EP0230967B1 (fr)
JP (1)	JPS62169770A (fr)
KR (1)	KR910000659B1 (fr)
CN (1)	CN1013111B (fr)
AT (1)	ATE68790T1 (fr)
AU (1)	AU590042B2 (fr)
CS (1)	CS258147B2 (fr)
DD (1)	DD264431A5 (fr)
DE (1)	DE3773950D1 (fr)
DK (1)	DK35887A (fr)
FI (1)	FI82931C (fr)
GB (1)	GB2185744B (fr)
HU (1)	HU197883B (fr)
IE (1)	IE870167L (fr)
IL (1)	IL81317A (fr)
IS (1)	IS3190A7 (fr)
MC (1)	MC1795A1 (fr)
MT (1)	MTP996B (fr)
MW (1)	MW187A1 (fr)
NO (1)	NO167385C (fr)
NZ (1)	NZ218987A (fr)
OA (1)	OA08469A (fr)
PH (1)	PH22879A (fr)
PL (1)	PL263796A1 (fr)
PT (1)	PT84181B (fr)
TN (1)	TNSN87006A1 (fr)
YU (1)	YU7087A (fr)
ZA (1)	ZA87407B (fr)
ZW (1)	ZW1087A1 (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL81317A (en) *	1986-01-23	1991-06-30	Hoffmann La Roche	1,2,4,5,6,7-hexahydro-4-benzazecine-3,8-dione derivatives,their preparation and pharmaceutical compositions containing them
IN167395B (fr) *	1987-07-21	1990-10-20	Hoffmann La Roche
US5239075A (en) *	1991-08-21	1993-08-24	Eli Lilly And Company	Process for the preparation of benzo (f) quinolinones
ES2169026T3 (es) *	1991-08-21	2002-07-01	Lilly Co Eli	Benzo(f)quinolinonas como inhibidores de 5-alfa-reductasa.
US5250539A (en) *	1991-08-21	1993-10-05	Eli Lilly And Company	Hexahydrobenzo[f]quinolinones
ES2125884T3 (es) *	1991-08-21	1999-03-16	Lilly Co Eli	Hexahidrobenzo(f)quinolinonas como inhibidores de la 5-alfa-reductasa.
WO1994022444A1 (fr) *	1993-03-29	1994-10-13	Smithkline Beecham Corporation	Composes tricycliques utilises pour inhiber l'agregation plaquettaire
GB9317314D0 (en) *	1993-08-20	1993-10-06	Smithkline Beecham Corp	Compounds
DE69515321T2 (de) *	1994-09-20	2000-08-24	The Regents Of The University Of California, Oakland	Brefeldin a und analoge zur verbesserung synaptischer übertragungen
US20050067341A1 (en) *	2003-09-25	2005-03-31	Green Dennis H.	Continuous production membrane water treatment plant and method for operating same
US7094331B2 (en) *	2003-11-05	2006-08-22	Marathon Ashland Petroleum Llc	Viscosity modification of heavy hydrocarbons using dihydric alcohols
US20090263439A1 (en) *	2008-04-18	2009-10-22	The Procter & Gamble Company	Antimicrobial Preservative Free Wipe
CN106117028B (zh) *	2016-06-14	2019-01-01	浙江永太药业有限公司	一种制备卤代-3,4-二氢-1h-2-萘酮的工艺方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE442586A (fr) *	1940-07-31
JPS5129710B2 (fr) *	1972-09-09	1976-08-27
US4341786A (en) *	1981-03-02	1982-07-27	Smithkline Corporation	Pharmaceutical compositions and method of producing central alpha1 agonist activity utilizing octahydrobenzo[f]quinoline compounds
US4521423A (en) *	1983-10-31	1985-06-04	Ayerst, Mckenna & Harrison, Ltd.	7,8,9,10-Tetrahydrobenzo[h]quinolin-9-amine derivatives and compositions and methods for treating depression employing them
IL81317A (en) *	1986-01-23	1991-06-30	Hoffmann La Roche	1,2,4,5,6,7-hexahydro-4-benzazecine-3,8-dione derivatives,their preparation and pharmaceutical compositions containing them

1987
- 1987-01-20 IL IL81317A patent/IL81317A/xx unknown
- 1987-01-20 AT AT87100733T patent/ATE68790T1/de not_active IP Right Cessation
- 1987-01-20 CS CS87418A patent/CS258147B2/cs unknown
- 1987-01-20 DE DE8787100733T patent/DE3773950D1/de not_active Expired - Lifetime
- 1987-01-20 FI FI870220A patent/FI82931C/fi not_active IP Right Cessation
- 1987-01-20 PH PH34744A patent/PH22879A/en unknown
- 1987-01-20 EP EP87100733A patent/EP0230967B1/fr not_active Expired - Lifetime
- 1987-01-20 ZA ZA87407A patent/ZA87407B/xx unknown
- 1987-01-20 YU YU00070/87A patent/YU7087A/xx unknown
- 1987-01-20 MW MW1/87A patent/MW187A1/xx unknown
- 1987-01-20 NZ NZ218987A patent/NZ218987A/en unknown
- 1987-01-21 ZW ZW10/87A patent/ZW1087A1/xx unknown
- 1987-01-21 DD DD87299380A patent/DD264431A5/de unknown
- 1987-01-21 US US07/005,712 patent/US4732979A/en not_active Expired - Fee Related
- 1987-01-21 HU HU87163A patent/HU197883B/hu not_active IP Right Cessation
- 1987-01-22 IE IE870167A patent/IE870167L/xx unknown
- 1987-01-22 AU AU67911/87A patent/AU590042B2/en not_active Ceased
- 1987-01-22 PT PT84181A patent/PT84181B/pt not_active IP Right Cessation
- 1987-01-22 DK DK035887A patent/DK35887A/da not_active Application Discontinuation
- 1987-01-22 IS IS3190A patent/IS3190A7/is unknown
- 1987-01-22 CN CN87100312A patent/CN1013111B/zh not_active Expired
- 1987-01-22 TN TNTNSN87006A patent/TNSN87006A1/fr unknown
- 1987-01-22 MC MC871868A patent/MC1795A1/fr unknown
- 1987-01-22 MT MT996A patent/MTP996B/xx unknown
- 1987-01-22 NO NO870280A patent/NO167385C/no unknown
- 1987-01-22 JP JP62011477A patent/JPS62169770A/ja active Pending
- 1987-01-22 GB GB8701416A patent/GB2185744B/en not_active Expired
- 1987-01-23 KR KR1019870000533A patent/KR910000659B1/ko not_active Expired
- 1987-01-23 PL PL1987263796A patent/PL263796A1/xx unknown
- 1987-01-23 OA OA59052A patent/OA08469A/fr unknown
- 1987-11-18 US US07/121,987 patent/US4749791A/en not_active Expired - Fee Related
1988
- 1988-02-11 US US07/154,760 patent/US4876340A/en not_active Expired - Fee Related
1989
- 1989-08-17 US US07/395,380 patent/US4957911A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
PT84181A (pt)	1987-02-01
ATE68790T1 (de)	1991-11-15
NO870280D0 (no)	1987-01-22
CS41887A2 (en)	1987-11-12
IS3190A7 (is)	1987-07-24
FI82931C (fi)	1991-05-10
DK35887D0 (da)	1987-01-22
DK35887A (da)	1987-07-24
NO167385C (no)	1991-10-30
US4732979A (en)	1988-03-22
PT84181B (pt)	1989-09-14
JPS62169770A (ja)	1987-07-25
CN87100312A (zh)	1987-09-09
MC1795A1 (fr)	1987-10-22
GB8701416D0 (en)	1987-02-25
EP0230967A2 (fr)	1987-08-05
GB2185744A (en)	1987-07-29
NO870280L (no)	1987-07-24
IE870167L (en)	1987-07-23
PH22879A (en)	1989-01-19
US4749791A (en)	1988-06-07
NO167385B (no)	1991-07-22
KR910000659B1 (ko)	1991-01-31
MTP996B (en)	1987-08-21
PL263796A1 (en)	1988-10-27
YU7087A (en)	1988-06-30
EP0230967B1 (fr)	1991-10-23
US4957911A (en)	1990-09-18
OA08469A (fr)	1988-07-29
MW187A1 (en)	1987-10-14
AU6791187A (en)	1987-07-30
KR870007132A (ko)	1987-08-17
ZA87407B (en)	1987-09-30
CN1013111B (zh)	1991-07-10
DE3773950D1 (de)	1991-11-28
EP0230967A3 (en)	1988-08-31
CS258147B2 (en)	1988-07-15
TNSN87006A1 (fr)	1990-01-01
HUT44519A (en)	1988-03-28
IL81317A0 (en)	1987-08-31
FI870220A0 (fi)	1987-01-20
GB2185744B (en)	1989-12-06
US4876340A (en)	1989-10-24
HU197883B (en)	1989-06-28
ZW1087A1 (en)	1987-08-12
FI870220A7 (fi)	1987-07-24
FI82931B (fi)	1991-01-31
IL81317A (en)	1991-06-30
AU590042B2 (en)	1989-10-26
NZ218987A (en)	1990-04-26

Publication	Publication Date	Title
DE69722858T2 (de)	2004-05-13	Intimale verdickungsinhibitoren
DD141828A5 (de)	1980-05-21	Verfahren zur herstellung von 1-(p-methoxybenzoyl)-2-pyrolidinon
EP0230967B1 (fr)	1991-10-23	Derivés de benzazécine
DE4430639A1 (de)	1996-03-07	Verwendung von 5-substituierten Pyridin- und Hexahydrochinolin-3-carbonsäurederivaten
CH673652A5 (fr)	1990-03-30
DE3125471A1 (de)	1982-03-18	"piperazinderivate, verfahren zu ihrer herstellung und arzneimittel, die diese verbindungen enthalten"
EP0105210B1 (fr)	1987-03-04	Dérivés de l'isoquinoléine, leur procédé de préparation compositions pharmaceutiques les contenant et leur utilisation
EP0002672B1 (fr)	1981-08-26	Pyrrolidines substituées, procédé pour leur préparation et médicaments les contenant
EP0170861B1 (fr)	1988-03-09	Composés d'aminocarbonylméthoxy-3-phényl-5-pyrazol, procédé de leur préparation et les compositions pharmaceutiques les contenant
DD277071A5 (de)	1990-03-21	Hydrozimtsaeurederivate
DE3503074A1 (de)	1985-08-08	Hydantoinderivate, verfahren zu deren herstellung und arzneimittel, welche diese enthalten
DE2749584A1 (de)	1978-05-18	Ueberbrueckte geminale diphenylpiperidine, verfahren zu ihrer herstellung und sie enthaltende arzneimittel
DE2416491A1 (de)	1974-10-24	Heterocyclische ester von alkylphenylbenzopyranen
EP0013424B1 (fr)	1982-11-17	Spiro(dibenzo(b,f)thiépine-pipéridines), produits intermédiaires pour leur préparation et médicaments les contenant
DE1620151B1 (de)	1971-07-15	10-Piperazino-dibenzo(a,d)cycloheptadienderivate und Verfahren zu ihrer Herstellung
DD251982A5 (de)	1987-12-02	Verfahren zur herstellung von neuen in 11-stellung substituierten 5,11-dihydro-6h-pyride-(2,3-b)(1,4) benzodiazipin-6-onen
DE3439157C2 (fr)	1992-10-08
DE3874361T2 (de)	1993-03-25	Als analgetika verwendbare 1-((4-morpholinyl)alkyl)-1h-indole und deren herstellung.
EP0054672A1 (fr)	1982-06-30	Composés du type lactame, compositions pharmaceutiques les contenant et procédé de préparation de ces composés et compositions pharmaceutiques
EP0714301A1 (fr)	1996-06-05	Utilisation comme medicaments d'esters d'acide 1-4-dihydropyridin dicarboxylique n-alkyles
DE2218138A1 (de)	1972-11-23	2-Amino-thieno eckige Klammer auf 2,3e eckige Klammer zu eckige Klammer auf 1,4 eckige Klammer zu diazepin-Verbindungen
EP0066303A1 (fr)	1982-12-08	Azidométhyl-2-benzodiazépines 1,4, leurs sels, leur procédé de préparation et produits pharmaceutiques qui les contiennent
DE2854941A1 (de)	1980-07-10	Indolo eckige klammer auf 3.2-b eckige klammer zu chinuclidine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
DE1620151C (de)	1972-02-17	10 Piperazino dibenzo eckige Klammer auf a,d eckige Klammer zu cycloheptadien derivate und Verfahren zu ihrer Herstel lung
EP0161478A2 (fr)	1985-11-21	Dérivés de 1-(2'-(substituée)-5',6',7',8'-tétra-(hydro)-4'-(oxo)-quinazol-6-yl)-3,4-di-(hydro)-6,7-di-(substituée)-isoquinoline, procédé pour leur préparation et médicaments les contenant