DE2549568C3 - 2,6-Dimethyl-3-methoxycarbonyl-4- (2'-nitrophenyl)-1,4-dihydropyridin-5- carbonsäureisobutylester, mehrere Verfahren zu seiner Herstellung sowie ihn enthaltende Arzneimittel - Google Patents
2,6-Dimethyl-3-methoxycarbonyl-4- (2'-nitrophenyl)-1,4-dihydropyridin-5- carbonsäureisobutylester, mehrere Verfahren zu seiner Herstellung sowie ihn enthaltende ArzneimittelInfo
- Publication number
- DE2549568C3 DE2549568C3 DE2549568A DE2549568A DE2549568C3 DE 2549568 C3 DE2549568 C3 DE 2549568C3 DE 2549568 A DE2549568 A DE 2549568A DE 2549568 A DE2549568 A DE 2549568A DE 2549568 C3 DE2549568 C3 DE 2549568C3
- Authority
- DE
- Germany
- Prior art keywords
- formula
- acetoacetate
- isobutyl
- ester
- dimethyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 6
- 239000003814 drug Substances 0.000 title claims description 4
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 title claims 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- 239000003960 organic solvent Substances 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 12
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 6
- -1 ethyl benzylidene acetoacetate Chemical compound 0.000 claims description 6
- ZYXNLVMBIHVDRH-UHFFFAOYSA-N 2-Methylpropyl 3-oxobutanoate Chemical compound CC(C)COC(=O)CC(C)=O ZYXNLVMBIHVDRH-UHFFFAOYSA-N 0.000 claims description 5
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 claims description 5
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 claims description 5
- 230000005923 long-lasting effect Effects 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 2
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 claims description 2
- VQZSDRXKLXBRHJ-UHFFFAOYSA-N diethyl 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1 VQZSDRXKLXBRHJ-UHFFFAOYSA-N 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 235000019441 ethanol Nutrition 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 239000002904 solvent Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 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
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 239000011435 rock Substances 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BUHJNRJEBAWMIF-DAXSKMNVSA-N 2-methylpropyl (Z)-2-aminobut-2-enoate Chemical compound C(C(C)C)OC(\C(=C\C)\N)=O BUHJNRJEBAWMIF-DAXSKMNVSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 240000002470 Amphicarpaea bracteata Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000008055 alkyl aryl sulfonates Chemical class 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229920005610 lignin Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- VCDOXKMVZZSCQK-ARJAWSKDSA-N methyl (z)-2-aminobut-2-enoate Chemical compound COC(=O)C(\N)=C\C VCDOXKMVZZSCQK-ARJAWSKDSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- General Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (39)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2549568A DE2549568C3 (de) | 1975-11-05 | 1975-11-05 | 2,6-Dimethyl-3-methoxycarbonyl-4- (2'-nitrophenyl)-1,4-dihydropyridin-5- carbonsäureisobutylester, mehrere Verfahren zu seiner Herstellung sowie ihn enthaltende Arzneimittel |
| NO763608A NO145574C (no) | 1975-11-05 | 1976-10-22 | Analogifremgangsmaate til fremstilling av 2,6-dimetyl-3-metoksykarbonyl-4-(2`-nitrofenyl)-1,4-dihydropyridin-5-karboksylsyreisobutylester |
| JP51129540A JPS5259161A (en) | 1975-11-05 | 1976-10-29 | 1*44dihydroo2*66dimethyll44 phenyll3*55pyridineedicarbonic acid isobuthylmethyl preparation method and medicine thereof |
| BG035341A BG25078A3 (bg) | 1975-11-05 | 1976-11-01 | Метод за получаване на изобутилов естер на 2,6-диметил-3-метоксикарбонил -4-(нитрофенил)-1,4-дихидропиридин-5-карбоновата киселина |
| BG035342A BG25079A3 (bg) | 1975-11-05 | 1976-11-01 | Метод за получаване на изобутилов естер на 2,6-диметил-3-метоксикарбонил -4-(2'-нитрофенил)-1,4 дихидропиридин-5-карбоновата киселина |
| BG035343A BG24803A3 (bg) | 1975-11-05 | 1976-11-01 | Метод за получаване на изобутилов естер на 2,6-диметил-3-метоксикарбонил 4-(2'-нитрофенил)-1,4-дихидропиридин -5-карбоновата киселина |
| BG035344A BG24804A3 (bg) | 1975-11-05 | 1976-11-01 | Метод за получаване на изобутилов естер на 2,6-диметил-3-метоксикарбонил -4(2'-нитрофенил)-1,4-дихидропиридин-5-карбоновата киселина |
| BG035345A BG24805A3 (bg) | 1975-11-05 | 1976-11-01 | Метод за получаване на изобутилов естер на 2,6-диметил-3-метоксикарбонил -4(2'-нитрофенил)-1,4-дихидропиридин-5-карбоновата киселина |
| BG034575A BG24668A3 (bg) | 1975-11-05 | 1976-11-01 | Метод за получаване на изобутилов естер на 2-6-диметил-3- метоксикарбонил-4-(2'-нитрофенил)-1,4-дихидропиридин-5- карбоновата киселина |
| RO7688294A RO70295A (ro) | 1975-11-05 | 1976-11-02 | Procedeu de preparare a esterului izobutilic al acidului 2,6-dimetil-3-metoxicarbonil-4-(2'-nitrofenil)-1,4-dihidropiridin-5-carboxilic |
| NZ182502A NZ182502A (en) | 1975-11-05 | 1976-11-02 | 1,4-dihydro-2,6-dimethyl-3-methoxycarbonyl-5-isobut-oxycarbonyl-4-(21-nitrophenyl)-pyridine and pharmaceutical compositions |
| CH1381976A CH623038A5 (en) | 1975-11-05 | 1976-11-02 | Process for the preparation of novel isobutyl 2,6-dimethyl-3-methoxycarbonyl-4-(2'-nitrophenyl)-1,4-dihydropyridine- 5-carboxylate |
| GB45501/76A GB1516793A (en) | 1975-11-05 | 1976-11-02 | 1,4-dihydropyridine-3,5-dicarboxylic acid diester derivative several processes for its preparation and its use as a coronary therapeutic agent |
| CS767068A CS200499B2 (en) | 1975-11-05 | 1976-11-02 | Process for preparing isobutylestere of 2,6-dimethyl-3-methoxycarbonyl-4-/2-nitrophenyl/1,4-dihydropyridin-5-carboxylic acid |
| IL50817A IL50817A (en) | 1975-11-05 | 1976-11-02 | Isobutyl methyl-1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylate,its preparation and pharmaceutical compositions containing it |
| AT814276A AT352129B (de) | 1975-11-05 | 1976-11-03 | Verfahren zur herstellung des neuen 2,6- dimethyl-3-methoxycarbonyl-4-(2'-nitrophenyl)- 1,4-dihydropyridin-5-carbonsaeureisobutylesters |
| NLAANVRAGE7612198,A NL175915C (nl) | 1975-11-05 | 1976-11-03 | Werkwijze voor het bereiden van coronair werkzame preparaten, alsmede werkwijze voor het bereiden van een in dergelijke preparaten toe te passen 2,6-dimethyl-3-methoxycarbonyl-4-(2'-nitrofenyl) -1,4-dihydropyridine-5-carbonzure-ester. |
| PL1976193438A PL106084B1 (pl) | 1975-11-05 | 1976-11-03 | Sposob wytwarzania nowego estru izobutylowego kwasu 2,6-dwumetylo-3-metoksykarbonylo-4-/2'-nitrofenylo/1,4-dwuwodoropirydyno-5-karboksylowego |
| PL1976201800A PL105940B1 (pl) | 1975-11-05 | 1976-11-03 | Sposob wytwarzania nowego estru izobutylowego kwasu 2,6-dwumetylo-3-metoksykarbonylo-4-/2'-nitrofenylo/-1,4-dwuwodoropirydyno-5-karboksylowego |
| FI763160A FI60704C (fi) | 1975-11-05 | 1976-11-03 | Foerfarande foer framstaellning av terapeutiskt anvaendbar 2,6-dimetyl-3-metoxikarbonyl-4-(2'-nitrofenyl)-1,4-dihydropyridin-5-karboxylsyraisobutylester |
| LU76133A LU76133A1 (enExample) | 1975-11-05 | 1976-11-04 | |
| PT65797A PT65797B (de) | 1975-11-05 | 1976-11-04 | Peutikum seiner herstellung sowie seine verwendung als coronartheradropyridin-5-carbonsanreisobutylester mehrere verfahren zu2,6-dimethyl-3-methoxycarbonyl-4-(2'-nitrophenyl)-1,4-dihy |
| ES452986A ES452986A1 (es) | 1975-11-05 | 1976-11-04 | Procedimiento para preparar ester isobutilico de acido 2,6- dimetil-3-metoxicarbonil-4-(2'-nitrofenil)-1, 4-dihidropiri-din-5-carboxilico). |
| GR52093A GR61241B (en) | 1975-11-05 | 1976-11-04 | 2,6-dimethyl-3-methoxycarbonyl-4-(2-nitrophenyl)-1,4-dihydropyridin-5-isobutylester of carbonic acid preparation process thereof and use thereof as coronartherapeutical |
| LU88275C LU88275I2 (enExample) | 1975-11-05 | 1976-11-04 | |
| SE7612308A SE423542B (sv) | 1975-11-05 | 1976-11-04 | Sett att framstella 2,6-dimetyl-3metoxikarbonyl-4-(2'-nitrofenyl)-1,4-dihydropyridin-5-karbonsyraisobutylester |
| DK498476A DK146762C (da) | 1975-11-05 | 1976-11-04 | Analogifremgangsmaade til fremstilling af 2,6-dimethyl-3-methoxycarbonyl-4-(2'-nitrophenyl)-1,4-dihydropyridin-5-carboxylsyreisobutylester |
| ZA766622A ZA766622B (en) | 1975-11-05 | 1976-11-04 | A 1,4-dihydropyridine-3,5-dicarboxylic acid di-ester derivative several processes for its preparation and its use as a coronary therapeutic agent |
| CA264,921A CA1085406A (en) | 1975-11-05 | 1976-11-04 | Isobutyl methyl-1,4-dihydro-2,6-dimethyl-4-(2- nitrophenyl)-3,5-pyridindicarboxylate |
| IE2458/76A IE43984B1 (en) | 1975-11-05 | 1976-11-04 | A 1,4-dihydropyridine-3 5-dicarboxylic acid di-ester derivative, several processes for its preparation,and its use as a coronary therapeutic agent |
| BE172063A BE847968A (fr) | 1975-11-05 | 1976-11-04 | Ester isobutylique de l'acide 2,6-dimethyl-3-methoxyczrbonyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-5-carboxylique, son procede de preparation et medicament a usage coronarien le contenant |
| AU19358/76A AU498964B2 (en) | 1975-11-05 | 1976-11-05 | Isobutyl methyl 1, 4-dihydro-2, 6-dimethyl-4-(2 nitrophenyl)-3, 5-pyridine-dicarboxylate |
| FR7633488A FR2330395A1 (fr) | 1975-11-05 | 1976-11-05 | Ester isobutylique de l'acide 2,6-dimethyl-3-methoxycarbonyl-4-(2'nitrophenyl)-1,4-dihydropyridine-5-carboxylique, son procede de preparation et medicament a usage coronarien le contenant |
| CS776535A CS200500B2 (cs) | 1975-11-05 | 1977-10-07 | Způsob výroby isobutylesteru 2,6-dimethyl-3-methoxykarbonyl-4- -(2'-nitrofenyl)-1,4-dihydropyridin-5-karboxylové kyseliny |
| ES463166A ES463166A1 (es) | 1975-11-05 | 1977-10-13 | Procedimiento para preparar ester isobutilico del acido 2,6-dimetil-3-metoxicarbonil-4-(2'-nitrofenil)-1,4-dihidropiri- din-5-carboxilico. |
| US05/903,573 US4154839A (en) | 1975-11-05 | 1978-05-08 | 2,6-Dimethyl-3-carboxymethoxy-4-(2-nitrophenyl)-5-carbisobutoxy-1,4-dihydropyridine |
| CH567880A CH622779A5 (en) | 1975-11-05 | 1980-07-23 | Process for the preparation of novel isobutyl 2,6-dimethyl-3-methoxycarbonyl-4-(2'-nitrophenyl)-1,4-dihydropyridine- 5-carboxylate |
| HK126/81A HK12681A (en) | 1975-11-05 | 1981-04-02 | A 1,4-dihydropyridine-3.5-dicarboxylic acid di-ester derivative,several processes for its preparation,and its use as a coronary therapeutic agent |
| NL930035C NL930035I2 (nl) | 1975-11-05 | 1993-05-24 | Werkwijze voor het bereiden van coronair werkzame preparaten, alsmede werkwijze voor het bereiden van een in dergelijke preparaten toe te passen 2,6-dimethyl-3-methoxycarbonyl-4-(2'-nitrofenyl)-1,4-dihydropyridine-5-carbozure-ester. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2549568A DE2549568C3 (de) | 1975-11-05 | 1975-11-05 | 2,6-Dimethyl-3-methoxycarbonyl-4- (2'-nitrophenyl)-1,4-dihydropyridin-5- carbonsäureisobutylester, mehrere Verfahren zu seiner Herstellung sowie ihn enthaltende Arzneimittel |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2549568A1 DE2549568A1 (de) | 1977-05-18 |
| DE2549568B2 DE2549568B2 (de) | 1980-08-21 |
| DE2549568C3 true DE2549568C3 (de) | 1981-10-29 |
Family
ID=5960951
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2549568A Expired DE2549568C3 (de) | 1975-11-05 | 1975-11-05 | 2,6-Dimethyl-3-methoxycarbonyl-4- (2'-nitrophenyl)-1,4-dihydropyridin-5- carbonsäureisobutylester, mehrere Verfahren zu seiner Herstellung sowie ihn enthaltende Arzneimittel |
Country Status (27)
| Country | Link |
|---|---|
| JP (1) | JPS5259161A (enExample) |
| AT (1) | AT352129B (enExample) |
| AU (1) | AU498964B2 (enExample) |
| BE (1) | BE847968A (enExample) |
| BG (6) | BG25078A3 (enExample) |
| CA (1) | CA1085406A (enExample) |
| CH (2) | CH623038A5 (enExample) |
| CS (1) | CS200499B2 (enExample) |
| DE (1) | DE2549568C3 (enExample) |
| DK (1) | DK146762C (enExample) |
| ES (2) | ES452986A1 (enExample) |
| FI (1) | FI60704C (enExample) |
| FR (1) | FR2330395A1 (enExample) |
| GB (1) | GB1516793A (enExample) |
| GR (1) | GR61241B (enExample) |
| HK (1) | HK12681A (enExample) |
| IE (1) | IE43984B1 (enExample) |
| IL (1) | IL50817A (enExample) |
| LU (2) | LU88275I2 (enExample) |
| NL (2) | NL175915C (enExample) |
| NO (1) | NO145574C (enExample) |
| NZ (1) | NZ182502A (enExample) |
| PL (2) | PL106084B1 (enExample) |
| PT (1) | PT65797B (enExample) |
| RO (1) | RO70295A (enExample) |
| SE (1) | SE423542B (enExample) |
| ZA (1) | ZA766622B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4146630A (en) * | 1976-11-12 | 1979-03-27 | Boehringer Mannheim Gmbh | Blood pressure lowering and adrenergic β-receptor inhibiting 3-(4-phenoxymethylpiperidino)-propyl-phenyl ethers |
| JPS55301A (en) * | 1978-02-14 | 1980-01-05 | Yamanouchi Pharmaceut Co Ltd | 1,4-dihydropyridine-3,5-dicarboxylic ester derivative and its preparation |
| DE3212736A1 (de) * | 1982-04-06 | 1983-10-13 | Bayer Ag, 5090 Leverkusen | Verwendung von dihydropyridinen in arzneimitteln mit salidiuretischer wirkung |
| DE3222367A1 (de) * | 1982-06-15 | 1983-12-15 | Bayer Ag, 5090 Leverkusen | Verwendung von 1,4-dihydropyridinen in antiarteriosklerotika und deren herstellung |
| JPS5982192U (ja) * | 1982-11-27 | 1984-06-02 | エムケ−精工株式会社 | 扉 |
| DE3312216A1 (de) * | 1983-04-05 | 1984-10-11 | Bayer Ag, 5090 Leverkusen | Verfahren zur herstellung von symmetrischen 1,4-dihydropyridincarbonsaeureestern |
| DE3312283A1 (de) * | 1983-04-05 | 1984-10-18 | Bayer Ag, 5090 Leverkusen | Verfahren zur herstellung von unsymmetrischen 1,4-dihydropyridincarbonsaeureestern |
| US4794111A (en) * | 1984-05-23 | 1988-12-27 | Bayer Aktiengesellschaft | Dihydropyridine preparations containing β-blockers |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2117571C3 (de) * | 1971-04-10 | 1979-10-11 | Bayer Ag, 5090 Leverkusen | Unsymmetrische 1,4-Dihydropyridin-33-dicarbonsäureester, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Arzneimittel |
-
1975
- 1975-11-05 DE DE2549568A patent/DE2549568C3/de not_active Expired
-
1976
- 1976-10-22 NO NO763608A patent/NO145574C/no unknown
- 1976-10-29 JP JP51129540A patent/JPS5259161A/ja active Granted
- 1976-11-01 BG BG035341A patent/BG25078A3/xx unknown
- 1976-11-01 BG BG035343A patent/BG24803A3/xx unknown
- 1976-11-01 BG BG035345A patent/BG24805A3/xx unknown
- 1976-11-01 BG BG035344A patent/BG24804A3/xx unknown
- 1976-11-01 BG BG034575A patent/BG24668A3/xx unknown
- 1976-11-01 BG BG035342A patent/BG25079A3/xx unknown
- 1976-11-02 RO RO7688294A patent/RO70295A/ro unknown
- 1976-11-02 CH CH1381976A patent/CH623038A5/de not_active IP Right Cessation
- 1976-11-02 GB GB45501/76A patent/GB1516793A/en not_active Expired
- 1976-11-02 IL IL50817A patent/IL50817A/xx unknown
- 1976-11-02 CS CS767068A patent/CS200499B2/cs unknown
- 1976-11-02 NZ NZ182502A patent/NZ182502A/xx unknown
- 1976-11-03 NL NLAANVRAGE7612198,A patent/NL175915C/xx not_active IP Right Cessation
- 1976-11-03 PL PL1976193438A patent/PL106084B1/pl unknown
- 1976-11-03 FI FI763160A patent/FI60704C/fi not_active IP Right Cessation
- 1976-11-03 AT AT814276A patent/AT352129B/de not_active IP Right Cessation
- 1976-11-03 PL PL1976201800A patent/PL105940B1/pl unknown
- 1976-11-04 ZA ZA766622A patent/ZA766622B/xx unknown
- 1976-11-04 LU LU88275C patent/LU88275I2/xx unknown
- 1976-11-04 LU LU76133A patent/LU76133A1/xx active Protection Beyond IP Right Term
- 1976-11-04 ES ES452986A patent/ES452986A1/es not_active Expired
- 1976-11-04 SE SE7612308A patent/SE423542B/xx not_active IP Right Cessation
- 1976-11-04 CA CA264,921A patent/CA1085406A/en not_active Expired
- 1976-11-04 GR GR52093A patent/GR61241B/el unknown
- 1976-11-04 IE IE2458/76A patent/IE43984B1/en not_active IP Right Cessation
- 1976-11-04 BE BE172063A patent/BE847968A/xx not_active IP Right Cessation
- 1976-11-04 DK DK498476A patent/DK146762C/da not_active IP Right Cessation
- 1976-11-04 PT PT65797A patent/PT65797B/pt unknown
- 1976-11-05 FR FR7633488A patent/FR2330395A1/fr active Granted
- 1976-11-05 AU AU19358/76A patent/AU498964B2/en not_active Expired
-
1977
- 1977-10-13 ES ES463166A patent/ES463166A1/es not_active Expired
-
1980
- 1980-07-23 CH CH567880A patent/CH622779A5/de not_active IP Right Cessation
-
1981
- 1981-04-02 HK HK126/81A patent/HK12681A/xx unknown
-
1993
- 1993-05-24 NL NL930035C patent/NL930035I2/nl unknown
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Legal Events
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| OD | Request for examination | ||
| C3 | Grant after two publication steps (3rd publication) | ||
| V448 | Application of spc |
Free format text: PRODUCT NAME: NISOLDIPIN; REGISTRATION NO/DATE: 10143.00.00, 10143.01.00; 19900426 Spc suppl protection certif: 193 75 023 Filing date: 19930514 |
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| V457 | Spc granted |
Free format text: PRODUCT NAME: NISOLDIPIN; REGISTRATION NO/DATE: 10143.00.00, 10143.01.00; 19900426 Spc suppl protection certif: 193 75 023 Filing date: 19930514 |
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| V464 | Spc expired |
Free format text: PRODUCT NAME: NISOLDIPIN; REGISTRATION NO/DATE: 10143.00.00, 10143.01.00; 19900426 Spc suppl protection certif: 193 75 023 Filing date: 19930514 |