JPH0160465B2 - - Google Patents
Info
- Publication number
- JPH0160465B2 JPH0160465B2 JP58202874A JP20287483A JPH0160465B2 JP H0160465 B2 JPH0160465 B2 JP H0160465B2 JP 58202874 A JP58202874 A JP 58202874A JP 20287483 A JP20287483 A JP 20287483A JP H0160465 B2 JPH0160465 B2 JP H0160465B2
- Authority
- JP
- Japan
- Prior art keywords
- ester
- dihydropyridine
- dicarboxylic acid
- dimethyl
- fluoro
- 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
- -1 aldehyde compound Chemical class 0.000 claims description 134
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- 239000002904 solvent Substances 0.000 description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 230000000704 physical effect Effects 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 230000000144 pharmacologic effect Effects 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 6
- 230000001077 hypotensive effect Effects 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 229960001597 nifedipine Drugs 0.000 description 5
- WLDHPJSICUOHTH-UHFFFAOYSA-N 2-fluoro-3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1F WLDHPJSICUOHTH-UHFFFAOYSA-N 0.000 description 4
- XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- VVXFDFQEIRGULC-UHFFFAOYSA-N 2-fluoro-5-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=O)=C1 VVXFDFQEIRGULC-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- IEIIDOGBEQCWHP-UHFFFAOYSA-N dimethyl 4-(3-chloro-2-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC(Cl)=C1F IEIIDOGBEQCWHP-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 230000005923 long-lasting effect Effects 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- BBBJXPCSKOPGLI-UHFFFAOYSA-N 2-propoxyethyl 3-oxobutanoate Chemical compound CCCOCCOC(=O)CC(C)=O BBBJXPCSKOPGLI-UHFFFAOYSA-N 0.000 description 2
- YAOZCMANASAVFN-UHFFFAOYSA-N 3-chloro-2-fluorobenzaldehyde Chemical compound FC1=C(Cl)C=CC=C1C=O YAOZCMANASAVFN-UHFFFAOYSA-N 0.000 description 2
- MSBQBBXLDJSJJL-UHFFFAOYSA-N 4-(2-fluoro-3-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1F MSBQBBXLDJSJJL-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 230000004531 blood pressure lowering effect Effects 0.000 description 2
- JGOTXCCXOKQEIL-UHFFFAOYSA-N dimethyl 4-(2-fluoro-5-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC([N+]([O-])=O)=CC=C1F JGOTXCCXOKQEIL-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 230000000304 vasodilatating effect Effects 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- XUCYJGMIICONES-UHFFFAOYSA-N 1-fluoro-2-methyl-4-nitrobenzene Chemical compound CC1=CC([N+]([O-])=O)=CC=C1F XUCYJGMIICONES-UHFFFAOYSA-N 0.000 description 1
- NBCNUIXYBLFJMI-UHFFFAOYSA-N 2-fluoro-1-methyl-3-nitrobenzene Chemical compound CC1=CC=CC([N+]([O-])=O)=C1F NBCNUIXYBLFJMI-UHFFFAOYSA-N 0.000 description 1
- PLHCSZRZWOWUBW-UHFFFAOYSA-N 2-methoxyethyl 3-oxobutanoate Chemical compound COCCOC(=O)CC(C)=O PLHCSZRZWOWUBW-UHFFFAOYSA-N 0.000 description 1
- PBJZBRWKTBIWOK-FPLPWBNLSA-N 2-propoxyethyl (z)-3-aminobut-2-enoate Chemical compound CCCOCCOC(=O)\C=C(\C)N PBJZBRWKTBIWOK-FPLPWBNLSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 150000004729 acetoacetic acid derivatives Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000003727 cerebral blood flow Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- YCKAGGHNUHZKCL-UHFFFAOYSA-N propan-2-yl 3-aminobut-2-enoate Chemical compound CC(C)OC(=O)C=C(C)N YCKAGGHNUHZKCL-UHFFFAOYSA-N 0.000 description 1
- GVIIRWAJDFKJMJ-UHFFFAOYSA-N propan-2-yl 3-oxobutanoate Chemical compound CC(C)OC(=O)CC(C)=O GVIIRWAJDFKJMJ-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- FDCJOQNCHBIAOV-WAYWQWQTSA-N tert-butyl (z)-3-aminobut-2-enoate Chemical compound C\C(N)=C\C(=O)OC(C)(C)C FDCJOQNCHBIAOV-WAYWQWQTSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20287483A JPS6094963A (ja) | 1983-10-31 | 1983-10-31 | １，４−ジヒドロピリジン−３，５−ジカルボン酸ジエステル誘導体及びその製造法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20287483A JPS6094963A (ja) | 1983-10-31 | 1983-10-31 | １，４−ジヒドロピリジン−３，５−ジカルボン酸ジエステル誘導体及びその製造法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6094963A JPS6094963A (ja) | 1985-05-28 |
| JPH0160465B2 true JPH0160465B2 (fr) | 1989-12-22 |
Family
ID=16464624
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20287483A Granted JPS6094963A (ja) | 1983-10-31 | 1983-10-31 | １，４−ジヒドロピリジン−３，５−ジカルボン酸ジエステル誘導体及びその製造法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6094963A (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR940003492B1 (ko) * | 1988-10-27 | 1994-04-23 | 주식회사 유한양행 | 1,4-디하이드로피리딘유도체 및 그의 제조방법 |
| DE59410255D1 (de) * | 1993-12-10 | 2003-04-17 | Bayer Ag | Phenyl-substituierte 1,4-Dihydropyridine mit cerebraler Aktivität |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4888880A (fr) * | 1972-02-22 | 1973-11-21 | ||
| JPS49127979A (fr) * | 1973-04-20 | 1974-12-07 | ||
| JPS577468A (en) * | 1980-05-13 | 1982-01-14 | Bayer Ag | Novel 1,4-dihydropyridine compound |
-
1983
- 1983-10-31 JP JP20287483A patent/JPS6094963A/ja active Granted
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4888880A (fr) * | 1972-02-22 | 1973-11-21 | ||
| JPS49127979A (fr) * | 1973-04-20 | 1974-12-07 | ||
| JPS577468A (en) * | 1980-05-13 | 1982-01-14 | Bayer Ag | Novel 1,4-dihydropyridine compound |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6094963A (ja) | 1985-05-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4772621A (en) | Antihypertensive diphenylpropyl aminopropyl ester of 1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylic acid | |
| US4772596A (en) | Dihydropyridine derivatives, their preparation and their use | |
| US4707486A (en) | Diaryl piperidine containing esters of 1,4-dihydropyridines and coronary therapeutic use | |
| JPH07600B2 (ja) | 新規な光学的活性の１，４−ジヒドロピリジン化合物の製造法 | |
| JPS63139182A (ja) | チアゾリジンジオン誘導体の製造法 | |
| HU198909B (en) | Process for producing pyridine-dicarbocylic acid esters | |
| US4578395A (en) | Certain aralkylaminoalkyl esters of 1,4 dihydropyridines as antihypertensive | |
| CA1330994C (fr) | Derives flavone | |
| US4600778A (en) | Process for the preparation of 1,4-dihydropyridinedicarboxylic esters | |
| JPH021478A (ja) | 二置換ピリジン類 | |
| US4607041A (en) | Antihypertensive 2-phenyl Hantzsch dihydropyridines | |
| JPS61257983A (ja) | １，４−ジヒドロピリジン及びこれを有効成分とする医薬組成物 | |
| JPH0160465B2 (fr) | ||
| EP0371492B1 (fr) | Procédé pour la préparation de dérivés de 1,4-dihydropyridine | |
| US4686217A (en) | Calcium antagonist 2-fluoroalkyl-1,4-dihydropyridines | |
| US4898865A (en) | [4-(6-Oxo-1,4,5,6-tetrahydro-3-pyridazinyl) anilino hexyl 1,4-dihydro-2,6 Di methyl 5 nitro 4 aryl pyridine 3-carboxylates | |
| JP3100444B2 (ja) | １，４−ジヒドロピリジン誘導体及びその製造方法 | |
| JPS60136558A (ja) | １，４−ジヒドロピリジン誘導体 | |
| KR100578425B1 (ko) | 캐테콜 히드라진 유도체, 이의 제조 방법 및 이를 함유한 약제학적 조성물 | |
| JPH0466233B2 (fr) | ||
| JPH0160466B2 (fr) | ||
| FI94242C (fi) | Menetelmä heterosyklisten johdannaisten valmistamiseksi | |
| JP2523026B2 (ja) | α，β―不飽和ケトン及びケトオキシム誘導体 | |
| JPH06199849A (ja) | ４−ヘテロシクロフエニル−置換されたジヒドロピリジン類 | |
| EP0242950B1 (fr) | Dihydropyridines, leur procédé de préparation et leur utilisation comme médicaments |