FI79700C - Foerfarande foer framstaellning av nya, farmaceutiskt anvaendbara dihydropyridin-derivat. - Google Patents
Foerfarande foer framstaellning av nya, farmaceutiskt anvaendbara dihydropyridin-derivat. Download PDFInfo
- Publication number
- FI79700C FI79700C FI831604A FI831604A FI79700C FI 79700 C FI79700 C FI 79700C FI 831604 A FI831604 A FI 831604A FI 831604 A FI831604 A FI 831604A FI 79700 C FI79700 C FI 79700C
- Authority
- FI
- Finland
- Prior art keywords
- piperazinyl
- compound
- ethyl
- dihydropyridine
- dimethyl
- Prior art date
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- 125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 0.000 title claims abstract description 19
- 229940085304 dihydropyridine derivative selective calcium channel blockers with mainly vascular effects Drugs 0.000 title claims abstract description 12
- 238000000034 method Methods 0.000 title claims description 23
- 238000002360 preparation method Methods 0.000 title claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 13
- 150000002367 halogens Chemical class 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 4
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 4
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 167
- -1 4-benzhydryl-1-piperazinyl Chemical group 0.000 claims description 104
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- DJPHMTGYCPYPNC-UHFFFAOYSA-N ClC=1C=C(C=CC1)N1CCN(CC1)CCC1=C(N(C(=CC1C1=CC(=CC=C1)[N+](=O)[O-])C)C)C Chemical compound ClC=1C=C(C=CC1)N1CCN(CC1)CCC1=C(N(C(=CC1C1=CC(=CC=C1)[N+](=O)[O-])C)C)C DJPHMTGYCPYPNC-UHFFFAOYSA-N 0.000 claims 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 3
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 abstract description 3
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract description 2
- 230000000069 prophylactic effect Effects 0.000 abstract description 2
- 229940126585 therapeutic drug Drugs 0.000 abstract description 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 3
- 125000004076 pyridyl group Chemical group 0.000 abstract 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- 125000004414 alkyl thio group Chemical group 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
- 239000011593 sulfur Chemical group 0.000 abstract 1
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- 238000000921 elemental analysis Methods 0.000 description 62
- XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 description 44
- 239000000843 powder Substances 0.000 description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
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- 229940093858 ethyl acetoacetate Drugs 0.000 description 28
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- 238000006243 chemical reaction Methods 0.000 description 26
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- 239000002904 solvent Substances 0.000 description 22
- 238000004519 manufacturing process Methods 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
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- YAQPWDDYTVXUQV-UHFFFAOYSA-N 2-(4-benzhydrylpiperazin-1-yl)ethyl 3-oxobutanoate Chemical compound C1CN(CCOC(=O)CC(=O)C)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 YAQPWDDYTVXUQV-UHFFFAOYSA-N 0.000 description 17
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- YPMPTULBFPFSEQ-PLNGDYQASA-N ethyl (z)-3-aminobut-2-enoate Chemical compound CCOC(=O)\C=C(\C)N YPMPTULBFPFSEQ-PLNGDYQASA-N 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
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- 229910021529 ammonia Inorganic materials 0.000 description 11
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- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- LLMLNAVBOAMOEE-UHFFFAOYSA-N 2,3-dichlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1Cl LLMLNAVBOAMOEE-UHFFFAOYSA-N 0.000 description 7
- CFXJRVSQIMFBKI-UHFFFAOYSA-N 2-[4-[bis(4-methylphenyl)methyl]piperazin-1-yl]ethyl 3-oxobutanoate Chemical compound C1CN(CCOC(=O)CC(=O)C)CCN1C(C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 CFXJRVSQIMFBKI-UHFFFAOYSA-N 0.000 description 7
- 206010020772 Hypertension Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 6
- 230000008327 renal blood flow Effects 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- JZIXMKBJXIIEKJ-UHFFFAOYSA-N 2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl 3-oxobutanoate Chemical compound C1CN(CCOC(=O)CC(=O)C)CCN1C1=CC=C(F)C=C1 JZIXMKBJXIIEKJ-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 230000004087 circulation Effects 0.000 description 5
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 5
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
- RZTAMFZIAATZDJ-UHFFFAOYSA-N felodipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-UHFFFAOYSA-N 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- ZZBUJGAZPOHFJB-UHFFFAOYSA-N 2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl 3-oxobutanoate Chemical compound C1CN(CCOC(=O)CC(=O)C)CCN1C1=CC=CC(Cl)=C1 ZZBUJGAZPOHFJB-UHFFFAOYSA-N 0.000 description 4
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- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
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- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 4
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- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- 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
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP8200159 | 1982-05-10 | ||
PCT/JP1982/000159 WO1983004023A1 (en) | 1982-05-10 | 1982-05-10 | Dihydropyridine derivatives |
PCT/JP1983/000008 WO1984002702A1 (en) | 1983-01-11 | 1983-01-11 | Dihydropyridine derivatives |
JP8300008 | 1983-01-11 |
Publications (4)
Publication Number | Publication Date |
---|---|
FI831604A0 FI831604A0 (fi) | 1983-05-09 |
FI831604L FI831604L (fi) | 1983-11-11 |
FI79700B FI79700B (fi) | 1989-10-31 |
FI79700C true FI79700C (fi) | 1990-02-12 |
Family
ID=26422991
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI831604A FI79700C (fi) | 1982-05-10 | 1983-05-09 | Foerfarande foer framstaellning av nya, farmaceutiskt anvaendbara dihydropyridin-derivat. |
Country Status (16)
Country | Link |
---|---|
US (1) | US4892875A (instruction) |
EP (1) | EP0094159B1 (instruction) |
KR (1) | KR880002357B1 (instruction) |
AT (1) | ATE50987T1 (instruction) |
AU (1) | AU556150B2 (instruction) |
CA (1) | CA1333487C (instruction) |
DK (1) | DK160984C (instruction) |
ES (3) | ES8607966A1 (instruction) |
FI (1) | FI79700C (instruction) |
GR (1) | GR78252B (instruction) |
HK (1) | HK3293A (instruction) |
IE (1) | IE56057B1 (instruction) |
IL (1) | IL68494A (instruction) |
MY (1) | MY102082A (instruction) |
NO (1) | NO159593C (instruction) |
PT (1) | PT76653B (instruction) |
Families Citing this family (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3377352D1 (en) * | 1982-06-03 | 1988-08-18 | Pierrel Spa | Dihydropyridines with an antagonistic activity to calcium, process for their preparation, and pharmaceutical compositions containing them |
CH663616A5 (de) * | 1983-06-21 | 1987-12-31 | Sandoz Ag | 1,4-dihydropyridin-derivate und sie enthaltende pharmazeutische zubereitungen. |
US5137889A (en) * | 1983-12-02 | 1992-08-11 | Otsuka Pharmaceutical Co., Ltd. | Dihydropyridine derivatives and process for preparing the same |
JPS60120861A (ja) * | 1983-12-02 | 1985-06-28 | Otsuka Pharmaceut Co Ltd | ジヒドロピリジン誘導体 |
GB8403866D0 (en) * | 1984-02-14 | 1984-03-21 | Recordati Chem Pharm | Diphenylalkylaminoalkyl esters |
IE57810B1 (en) * | 1984-03-27 | 1993-04-21 | Delagrange Lab | 1,4-dihydropyridine derivatives,their preparation and their use |
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US4755512A (en) * | 1984-04-11 | 1988-07-05 | Bristol-Myers Company | Pharmaceutically useful dihydropyridinyldicarboxylate amides and esters incorporating arylpiperazinylalkyl moities |
FI853478A7 (fi) * | 1984-09-14 | 1986-03-15 | Ciba Geigy Ag | Menetelmä fenyylialkyyliyhdisteiden valmistamiseksi. |
ATE107284T1 (de) * | 1984-09-28 | 1994-07-15 | Byk Gulden Lomberg Chem Fab | Neue diarylverbindungen. |
IT1196272B (it) * | 1984-09-28 | 1988-11-16 | Poli Ind Chimica Spa | Derivati di 1,4-diidropiridina e composizioni farmaceutiche che li contengono |
NL8503262A (nl) * | 1984-12-10 | 1986-07-01 | Sandoz Ag | 1,4-dihydropyridinederivaten, werkwijze voor het bereiden van deze derivaten en farmaceutische preparaten die ze bevatten. |
JPS62501972A (ja) * | 1984-12-21 | 1987-08-06 | ビク・グルデン・ロムベルク・ヘミッシエ・フアブリ−ク・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 新規ピペラジン誘導体 |
IT1191845B (it) * | 1986-01-20 | 1988-03-23 | Dompe Farmaceutici Spa | Alchiloli derivati farmacologicamente attivi |
DK114587A (da) * | 1986-03-12 | 1987-09-13 | Byk Gulden Lomberg Chem Fab | Monocycliske esterderivater |
US4814455A (en) * | 1986-04-16 | 1989-03-21 | Bristol-Myers Company | Dihydro-3,5-dicarboxylates |
US4868181A (en) * | 1986-08-04 | 1989-09-19 | E. I. Du Pont De Nemours And Company | 1,4-dihydropyridine derivatives with calcium agonist and alpha1 -antagonist activity |
JPH0725750B2 (ja) * | 1987-12-18 | 1995-03-22 | 富士レビオ株式会社 | 1,4‐ジヒドロピリジン誘導体 |
EP0342577B1 (en) * | 1988-05-19 | 2000-03-15 | Yoshitomi Pharmaceutical Industries, Ltd. | Use of dihydropyridine derivatives for the prophylaxis or treatment of cerebral circulation disorders |
US5286869A (en) * | 1988-12-15 | 1994-02-15 | Fujirebio Kabushiki Kaisha | 1,4-dihydropyridine derivatives |
JP2838282B2 (ja) * | 1988-12-29 | 1998-12-16 | 吉富製薬株式会社 | 血管攣縮治療剤 |
USRE46117E1 (en) | 1999-12-22 | 2016-08-23 | Teva Pharmaceuticals International Gmbh | Modulators of dopamine neurotransmission |
SE9904724D0 (sv) | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission I |
SE9904723D0 (sv) | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission II |
CZ301790B6 (cs) * | 2000-04-11 | 2010-06-23 | Sankyo Company Limited | Farmaceutický prípravek obsahující blokátor vápníku |
AU2001284413A1 (en) * | 2000-08-30 | 2002-03-13 | Sankyo Company Limited | Medicinal compositions for preventing or treating heart failure |
WO2004017964A1 (en) | 2002-08-19 | 2004-03-04 | Pfizer Products Inc. | Combination therapy for hyperproliferative diseases |
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MXPA06013941A (es) | 2004-06-08 | 2007-12-10 | Neurosearch Sweden Ab | Fenilpiperidinas disustituidas, novedosas, como moduladores de la neurotransmision de dopamina y serotonina. |
SE0401465D0 (sv) | 2004-06-08 | 2004-06-08 | Carlsson A Research Ab | New substituted piperdines as modulators of dopamine neurotransmission |
ES2346452T3 (es) * | 2004-06-08 | 2010-10-15 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Nuevas fenilpiperidinas/piperazinas disustituidas utilizadas como moduladores de la neurotransmision de la dopamina. |
US7851629B2 (en) | 2004-06-08 | 2010-12-14 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Disubstituted phenylpiperidines as modulators of dopamine and serotonin neurotransmission |
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WO2006040155A1 (en) | 2004-10-13 | 2006-04-20 | Neurosearch Sweden Ab | Process for the synthesis of 4-(3-methanesulfonylphenyl)-1-n-propyl-piperidine |
SE529246C2 (sv) | 2005-10-13 | 2007-06-12 | Neurosearch Sweden Ab | Nya disubstituerade fenyl-piperidiner som modulatorer för dopaminneurotransmission |
US7741317B2 (en) | 2005-10-21 | 2010-06-22 | Bristol-Myers Squibb Company | LXR modulators |
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US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
TW200736245A (en) * | 2005-11-29 | 2007-10-01 | Sankyo Co | Acid addition salts of optically active dihydropyridine derivatives |
TW200806648A (en) * | 2005-11-29 | 2008-02-01 | Sankyo Co | Acid addition salts of dihydropyridine derivatives |
US7919506B2 (en) | 2006-03-10 | 2011-04-05 | Pfizer Inc. | Dibenzyl amine compounds and derivatives |
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CN101215258A (zh) * | 2008-01-21 | 2008-07-09 | 中国药科大学 | 二氢吡啶类钙拮抗剂化合物及其制备方法与医药用途 |
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WO2011023954A2 (en) * | 2009-08-27 | 2011-03-03 | Cipla Limited | Polymorphic forms of manidipine |
WO2012037665A1 (en) | 2010-09-24 | 2012-03-29 | Oral Delivery Technology Ltd. | Nitric oxide releasing amino acid ester for treatment of pulmonary hypertension and other respiratory conditions |
EP2787997A4 (en) | 2011-12-08 | 2015-05-27 | Ivax Int Gmbh | HYDROBROMIDE SALT OF PRIDOPIDINE |
WO2013152105A1 (en) | 2012-04-04 | 2013-10-10 | IVAX International GmbH | Pharmaceutical compositions for combination therapy |
CN102875451B (zh) * | 2012-04-05 | 2014-12-03 | 常州制药厂有限公司 | 一种盐酸马尼地平合成工艺的改进方法 |
CA2909442A1 (en) | 2013-04-17 | 2014-10-23 | Pfizer Inc. | N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases |
CN103351362A (zh) * | 2013-06-17 | 2013-10-16 | 张家港威胜生物医药有限公司 | 一种马尼地平中间体2-(4-二苯甲基哌嗪)乙基乙酰乙酸酯的制备方法 |
CN103467364B (zh) * | 2013-06-21 | 2015-07-15 | 四川海思科制药有限公司 | 一种盐酸马尼地平化合物 |
WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
CN106518806A (zh) * | 2016-09-07 | 2017-03-22 | 张家港威胜生物医药有限公司 | 一种马尼地平中间体2‑(4‑二苯甲基哌嗪)乙基乙酰乙酸酯的制备方法 |
CN106380442A (zh) * | 2016-09-07 | 2017-02-08 | 张家港威胜生物医药有限公司 | 一种钙离子通道拮抗剂马尼地平的制备方法 |
US11248001B2 (en) | 2019-01-18 | 2022-02-15 | Astrazeneca Ab | PCSK9 inhibitors and methods of use thereof |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3472853A (en) * | 1967-05-29 | 1969-10-14 | Sterling Drug Inc | 1-((pyrido(2,1-c)-s-triazolyl)-lower-alkyl)-4-substituted- piperazines |
DE2218644C3 (de) * | 1972-04-18 | 1982-08-19 | Bayer Ag, 5090 Leverkusen | Basische Ester von 1,4-Dihydropyridinen, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Arzneimittel |
DE2239815C2 (de) * | 1972-08-12 | 1983-02-10 | Bayer Ag, 5090 Leverkusen | 2-Alkylamino-dihydropyridine, Verfahren zu ihrer Herstellung sowie diese enthaltende Arzneimittel |
GB1455502A (en) * | 1973-02-20 | 1976-11-10 | Yamanouchi Pharma Co Ltd | 1,4-dihydropyridine derivatives |
JPS55301A (en) * | 1978-02-14 | 1980-01-05 | Yamanouchi Pharmaceut Co Ltd | 1,4-dihydropyridine-3,5-dicarboxylic ester derivative and its preparation |
DE2949464A1 (de) * | 1978-12-18 | 1980-06-26 | Sandoz Ag | Benzoxadiazole und benzothiadiazole, ihre herstellung und verwendung |
DE3022030A1 (de) * | 1980-06-12 | 1981-12-17 | Bayer Ag, 5090 Leverkusen | 4-thiazol- bzw. 4-imidazol-substituierte, 1,4-dihydropyridine, verfahren zu deren herstellung sowie diese enthaltende arzneimittel |
DE3042769A1 (de) * | 1980-11-13 | 1982-06-09 | Bayer Ag, 5090 Leverkusen | C-3 verknuepfte 1,4-dihydropyridine, ihre verwendung in arzneimitteln und verfahren zu ihrer herstellung |
CS228917B2 (en) * | 1981-03-14 | 1984-05-14 | Pfizer | Method of preparing substituted derivatives of 1,4-dihydropyridine |
JPS57175166A (en) * | 1981-04-23 | 1982-10-28 | Banyu Pharmaceut Co Ltd | Carbamoyloxyalkyl-1,4-dihydropyridine derivative and its preparation |
DE3269219D1 (en) * | 1981-11-17 | 1986-03-27 | Fisons Plc | Dihydropyridines, methods for their production and their formulation and use as pharmaceuticals |
-
1983
- 1983-04-15 EP EP83302139A patent/EP0094159B1/en not_active Expired
- 1983-04-15 AT AT83302139T patent/ATE50987T1/de active
- 1983-04-20 IE IE897/83A patent/IE56057B1/en not_active IP Right Cessation
- 1983-04-26 IL IL68494A patent/IL68494A/xx not_active IP Right Cessation
- 1983-05-02 AU AU14155/83A patent/AU556150B2/en not_active Ceased
- 1983-05-03 GR GR71283A patent/GR78252B/el unknown
- 1983-05-06 DK DK203083A patent/DK160984C/da not_active IP Right Cessation
- 1983-05-06 PT PT76653A patent/PT76653B/pt unknown
- 1983-05-06 NO NO831613A patent/NO159593C/no not_active IP Right Cessation
- 1983-05-07 KR KR1019830001951A patent/KR880002357B1/ko not_active Expired
- 1983-05-09 FI FI831604A patent/FI79700C/fi not_active IP Right Cessation
- 1983-05-09 CA CA000427690A patent/CA1333487C/en not_active Expired - Fee Related
- 1983-05-09 ES ES522199A patent/ES8607966A1/es not_active Expired
-
1985
- 1985-01-22 US US06/693,196 patent/US4892875A/en not_active Expired - Lifetime
- 1985-03-28 ES ES541668A patent/ES541668A0/es active Granted
- 1985-09-25 ES ES547275A patent/ES8701171A1/es not_active Expired
-
1987
- 1987-09-29 MY MYPI87002229A patent/MY102082A/en unknown
-
1993
- 1993-01-14 HK HK32/93A patent/HK3293A/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
DK203083D0 (da) | 1983-05-06 |
AU1415583A (en) | 1983-11-17 |
PT76653B (en) | 1986-01-27 |
ES547275A0 (es) | 1986-11-16 |
NO159593C (no) | 1989-01-18 |
ES8602661A1 (es) | 1985-12-01 |
ES541668A0 (es) | 1985-12-01 |
KR840004741A (ko) | 1984-10-24 |
KR880002357B1 (ko) | 1988-10-29 |
FI79700B (fi) | 1989-10-31 |
IL68494A0 (en) | 1983-07-31 |
IE56057B1 (en) | 1991-04-10 |
EP0094159A1 (en) | 1983-11-16 |
DK203083A (da) | 1983-11-11 |
EP0094159B1 (en) | 1990-03-14 |
GR78252B (instruction) | 1984-09-26 |
ES8607966A1 (es) | 1986-01-16 |
ES522199A0 (es) | 1986-01-16 |
ATE50987T1 (de) | 1990-03-15 |
ES8701171A1 (es) | 1986-11-16 |
CA1333487C (en) | 1994-12-13 |
AU556150B2 (en) | 1986-10-23 |
PT76653A (en) | 1983-06-01 |
HK3293A (en) | 1993-01-21 |
IE830897L (en) | 1983-11-10 |
FI831604A0 (fi) | 1983-05-09 |
NO159593B (no) | 1988-10-10 |
DK160984B (da) | 1991-05-13 |
MY102082A (en) | 1992-03-31 |
IL68494A (en) | 1988-01-31 |
NO831613L (no) | 1983-11-11 |
DK160984C (da) | 1991-11-11 |
FI831604L (fi) | 1983-11-11 |
US4892875A (en) | 1990-01-09 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
MA | Patent expired |
Owner name: TAKEDA CHEMICAL INDUSTRIES, LTD. |