CA1333487C - Dihydropyridine derivatives, their production and use - Google Patents
Dihydropyridine derivatives, their production and useInfo
- Publication number
- CA1333487C CA1333487C CA000427690A CA427690A CA1333487C CA 1333487 C CA1333487 C CA 1333487C CA 000427690 A CA000427690 A CA 000427690A CA 427690 A CA427690 A CA 427690A CA 1333487 C CA1333487 C CA 1333487C
- Authority
- CA
- Canada
- Prior art keywords
- piperazinyl
- dimethyl
- methyl
- dihydropyridine
- dicarboxylate
- 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 - Fee Related
Links
- 125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 0.000 title claims abstract description 20
- 229940085304 dihydropyridine derivative selective calcium channel blockers with mainly vascular effects Drugs 0.000 title abstract description 10
- 238000004519 manufacturing process Methods 0.000 title description 29
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 20
- 150000002367 halogens Chemical class 0.000 claims abstract description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 9
- 150000002431 hydrogen Chemical class 0.000 claims abstract 6
- 239000000203 mixture Substances 0.000 claims description 89
- 150000001875 compounds Chemical class 0.000 claims description 83
- 238000000034 method Methods 0.000 claims description 57
- XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 claims description 53
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
- -1 compound 2-(4-benzhydryl-1-piperazinyl)ethyl methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical class 0.000 claims description 40
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 claims description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 239000002904 solvent Substances 0.000 claims description 31
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 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 claims description 19
- 239000012634 fragment Substances 0.000 claims description 16
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 13
- 229910021529 ammonia Inorganic materials 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 12
- 230000000304 vasodilatating effect Effects 0.000 claims description 10
- 230000003276 anti-hypertensive effect Effects 0.000 claims description 9
- 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 claims description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- PVHUJELLJLJGLN-UHFFFAOYSA-N nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-UHFFFAOYSA-N 0.000 claims description 8
- 230000002490 cerebral effect Effects 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 230000002093 peripheral effect Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- WJWCMSXFBYUXPC-UHFFFAOYSA-N 2-[4-(3-chloro-4-methylphenyl)piperazin-1-yl]ethyl 3-oxobutanoate Chemical compound C1CN(CCOC(=O)CC(=O)C)CCN1C1=CC=C(C)C(Cl)=C1 WJWCMSXFBYUXPC-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- PZVGOFSWURYHGZ-UHFFFAOYSA-N 2-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]ethyl 3-oxobutanoate Chemical compound C1CN(CCOC(=O)CC(=O)C)CCN1C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 PZVGOFSWURYHGZ-UHFFFAOYSA-N 0.000 claims description 3
- HYQMRVUKYOFWFJ-UHFFFAOYSA-N 5-o-[2-[4-[bis(4-chlorophenyl)methyl]piperazin-1-yl]ethyl] 3-o-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 HYQMRVUKYOFWFJ-UHFFFAOYSA-N 0.000 claims description 3
- YBBRQAXNTWMMFZ-UHFFFAOYSA-N 2,1,3-benzoxadiazole-4-carbaldehyde Chemical compound O=CC1=CC=CC2=NON=C12 YBBRQAXNTWMMFZ-UHFFFAOYSA-N 0.000 claims description 2
- CQNNDFCXAUIRQR-UHFFFAOYSA-N 2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl 3-oxobutanoate Chemical compound C1CN(CCOC(=O)CC(=O)C)CCN1C1=CC=CC(Cl)=C1Cl CQNNDFCXAUIRQR-UHFFFAOYSA-N 0.000 claims description 2
- STJVLLVXMVRROW-UHFFFAOYSA-N 2-[4-(2,5-dichlorophenyl)piperazin-1-yl]ethyl 3-oxobutanoate Chemical compound C1CN(CCOC(=O)CC(=O)C)CCN1C1=CC(Cl)=CC=C1Cl STJVLLVXMVRROW-UHFFFAOYSA-N 0.000 claims description 2
- YZFUMKWPTPFYDM-UHFFFAOYSA-N 5-o-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl] 3-o-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C=2C(=C(Cl)C=CC=2)Cl)C1C1=CC=CC([N+]([O-])=O)=C1 YZFUMKWPTPFYDM-UHFFFAOYSA-N 0.000 claims description 2
- RWOOOXDDDBMYIZ-UHFFFAOYSA-N 5-o-[2-[4-(3-chloro-4-methylphenyl)piperazin-1-yl]ethyl] 3-o-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C=2C=C(Cl)C(C)=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 RWOOOXDDDBMYIZ-UHFFFAOYSA-N 0.000 claims description 2
- WXMMYLIWDONTCS-UHFFFAOYSA-N 5-o-[2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl] 3-o-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C=2C=C(Cl)C=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 WXMMYLIWDONTCS-UHFFFAOYSA-N 0.000 claims description 2
- NRBUSEVADHMSJS-UHFFFAOYSA-N 5-o-[2-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]ethyl] 3-o-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 NRBUSEVADHMSJS-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- ANEBWFXPVPTEET-UHFFFAOYSA-N manidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ANEBWFXPVPTEET-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 26
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 12
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 10
- 239000005977 Ethylene Substances 0.000 claims 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 239000005864 Sulphur Substances 0.000 claims 2
- QHLMREIOTDBARK-UHFFFAOYSA-N 5-o-[2-(4-benzhydrylpiperazin-1-yl)ethyl] 3-o-methyl 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound C=1C=CC2=NON=C2C=1C1C(C(=O)OC)=C(C)NC(C)=C1C(=O)OCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 QHLMREIOTDBARK-UHFFFAOYSA-N 0.000 claims 1
- RZSVOKUMGGXIRS-UHFFFAOYSA-N 5-o-[2-[4-(2,5-dichlorophenyl)piperazin-1-yl]ethyl] 3-o-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C=2C(=CC=C(Cl)C=2)Cl)C1C1=CC=CC([N+]([O-])=O)=C1 RZSVOKUMGGXIRS-UHFFFAOYSA-N 0.000 claims 1
- XRZMYQPZDUJNKP-UHFFFAOYSA-N 5-o-[2-[4-[bis(4-methylphenyl)methyl]piperazin-1-yl]ethyl] 3-o-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC(C)=CC=2)C=2C=CC(C)=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 XRZMYQPZDUJNKP-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 11
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 8
- 125000004076 pyridyl group Chemical group 0.000 abstract description 7
- 125000003118 aryl group Chemical group 0.000 abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 abstract description 3
- 125000002947 alkylene group Chemical group 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
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract description 2
- 125000004414 alkyl thio 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
- XOCUXOWLYLLJLV-UHFFFAOYSA-N [O].[S] Chemical group [O].[S] XOCUXOWLYLLJLV-UHFFFAOYSA-N 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 183
- 238000000921 elemental analysis Methods 0.000 description 62
- 101150041968 CDC13 gene Proteins 0.000 description 56
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 56
- 239000000843 powder Substances 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 238000005245 sintering Methods 0.000 description 32
- 229910052799 carbon Inorganic materials 0.000 description 28
- 239000013078 crystal Substances 0.000 description 27
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 25
- 229940093858 ethyl acetoacetate Drugs 0.000 description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 239000000460 chlorine Substances 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 230000008327 renal blood flow Effects 0.000 description 14
- YPMPTULBFPFSEQ-PLNGDYQASA-N ethyl (z)-3-aminobut-2-enoate Chemical compound CCOC(=O)\C=C(\C)N YPMPTULBFPFSEQ-PLNGDYQASA-N 0.000 description 13
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- MOTRZVVGCFFABN-UHFFFAOYSA-N hexane;2-propan-2-yloxypropane Chemical compound CCCCCC.CC(C)OC(C)C MOTRZVVGCFFABN-UHFFFAOYSA-N 0.000 description 9
- 125000006519 CCH3 Chemical group 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 230000000694 effects Effects 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 244000215068 Acacia senegal Species 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 229920000084 Gum arabic Polymers 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 235000010489 acacia gum Nutrition 0.000 description 6
- 239000000205 acacia gum Substances 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 description 5
- 230000000916 dilatatory effect 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
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- 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 4
- 241001465754 Metazoa Species 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000008120 corn starch Substances 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
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
- 229960001597 nifedipine Drugs 0.000 description 4
- 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 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- PZYZNVGUXXOFHD-UHFFFAOYSA-N 2-(4-phenylpiperazin-1-yl)ethyl 3-oxobutanoate Chemical compound C1CN(CCOC(=O)CC(=O)C)CCN1C1=CC=CC=C1 PZYZNVGUXXOFHD-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 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 3
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 3
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 3
- OCNFRPKRBALEIU-UHFFFAOYSA-N 3-(4-benzhydrylpiperazin-1-yl)propyl 3-oxobutanoate Chemical compound C1CN(CCCOC(=O)CC(=O)C)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 OCNFRPKRBALEIU-UHFFFAOYSA-N 0.000 description 3
- NMTUHPSKJJYGML-UHFFFAOYSA-N 3-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(C=O)=C1 NMTUHPSKJJYGML-UHFFFAOYSA-N 0.000 description 3
- IFKVIFIWJTVLPY-UHFFFAOYSA-N 5-o-[2-(4-benzhydrylpiperazin-1-yl)ethyl] 3-o-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;hydrate;dihydrochloride Chemical compound O.Cl.Cl.COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 IFKVIFIWJTVLPY-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000003944 halohydrins Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 230000000302 ischemic effect Effects 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
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000006229 isopropoxyethyl group Chemical group [H]C([H])([H])C([H])(OC([H])([H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- UVSBCUAQEZINCQ-UHFFFAOYSA-N methyl 3-formylbenzoate Chemical compound COC(=O)C1=CC=CC(C=O)=C1 UVSBCUAQEZINCQ-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- 125000006225 propoxyethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000523 sample Substances 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
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 239000003981 vehicle 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
-
- 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 |
---|---|---|---|
PCT/JP1982/000159 WO1983004023A1 (en) | 1982-05-10 | 1982-05-10 | Dihydropyridine derivatives |
JP82/00159 | 1982-05-10 | ||
JP83/00008 | 1983-01-11 | ||
PCT/JP1983/000008 WO1984002702A1 (en) | 1983-01-11 | 1983-01-11 | Dihydropyridine derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1333487C true CA1333487C (en) | 1994-12-13 |
Family
ID=26422991
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000427690A Expired - Fee Related CA1333487C (en) | 1982-05-10 | 1983-05-09 | Dihydropyridine derivatives, their production and use |
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)
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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 |
US4895846A (en) * | 1984-04-11 | 1990-01-23 | Bristol-Myers Company | Pharmaceutically useful dihydropyridinyldicarboxylate amides and esters incorporating arylpiperazinylalkyl moieties |
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 |
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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 |
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SE529246C2 (sv) | 2005-10-13 | 2007-06-12 | Neurosearch Sweden Ab | Nya disubstituerade fenyl-piperidiner som modulatorer för dopaminneurotransmission |
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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 |
FI79700C (fi) | 1990-02-12 |
ES8607966A1 (es) | 1986-01-16 |
ES522199A0 (es) | 1986-01-16 |
ATE50987T1 (de) | 1990-03-15 |
ES8701171A1 (es) | 1986-11-16 |
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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