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US 2004/0006110 A1Published application
1,4-dihydropyridine and pyridine compounds as calcium channel blockers
AssigneeVittal Mallya Scientific Research Foundation
InventorsPhani Kumar Pullela, Paramashivappa Rangappa, Srinivasa Rao Alapati, Pillarisetti V. Subbarao, Jeffrey A. Bibbs
Life of this patent
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Abstract
The present invention is directed in part towards methods of modulating the function of calcium channels with pyridine- or 1,4-dihydropyridine-based compounds. In addition, the invention describes methods of preventing and treating protein kinase-related abnormal conditions in organisms with a compound identified by the invention. Furthermore, the invention pertains to pyridine- or 1,4-dihydropyridine-based compounds and pharmaceutical compositions comprising these compounds.
Claims54
A compound of Formula I or II
- 36
- or a pharmaceutically acceptable salt, amide, ester, or prodrug thereof, where
- a) R1 is an straight-chain, branched, or cyclic alkyl group having greater than eight carbon atoms;
- b) R2-R9 are each independently selected from the group consisting of hydrogen, halogen, perhaloalkyl, nitro, amino, a diazo salt, optionally substituted lower alkyl, optionally substituted lower alkylene, optionally substituted lower alkoxy, optionally substituted lower alkoxyalkyl, optionally substituted lower alkoxyalkoxy, optionally substituted lower mercaptyl, optionally substituted lower mercaptoalkyl, optionally substituted lower mercaptomercaptyl, —C(O)OH, —OC(O)H, —C(O)OR, —OC(O)R, —C(S)OR, —OC(S)R, —C(O)SR, —SC(O)R, —C(S)SR, —SC(S)R, C-amido, N-amido, and optionally substituted five- or six-membered heteroaryl ring or optionally substituted six-membered aryl or heteroaryl ring,
- where the lower alkyl and the lower alkylene moieties are each independently and optionally substituted with one or more substituents selected from the group consisting of halogen, perhaloalkyl, nitro, amino, hydroxy, alkoxy, sulfhydryl, thioether, cyano, amido, ester, and
- 37
- where A is selected from the group consisting of oxygen, sulfur, and —NH and R12 is selected for the group consisting of hydrogen, hydroxy, alkoxy, haloalkoxy, halogen, haloalkyl, perhaloalkyl, nitro, amino, and a diazo salt, and n is between 0-4;
- and
- where the ring moieties are each independently and optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkylene,
- c) R10 and R11, in the compound of Formula I are each independently selected from the group consisting of hydrogen and lower alkyl.
7 more elements
A compound selected from the group consisting of
- diethyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2,6-dimethyl-3,5-carboxy pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2-methyl-6-(2′-mercapto-1′H-benzimidazolyl) methyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2-methyl-6-(2′-mercapto-1′H-benzimidazolyl) methyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2-methyl-6-(2′-mercapto-1′H-benzimidazolyl) methyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2-methyl-6-(2′-mercapto-1′H-benzimidazolyl) methyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2-methyl-6-(2′-mercapto-1′H-benzimidazolyl) methyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2-methyl-6-(2′-mercapto-1′H-benzimidazolyl) methyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2-methyl-6-(2′-mercapto-1′H-benzimidazolyl) methyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2-methyl-6-(2′-mercapto-1′H-benzimidazolyl) methyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2-methyl-6-(2′-mercapto-140 H-benzimidazolyl) methyl-3,5-pyridine dicarboxylate, 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2,6-dimethyl-3-ethyl-5-(methoxy ethyl) pyridine dicarboxylate,
- 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2,6-dimethyl-3-methyl-5-(methoxy ethyl) pyridine dicarboxylate,
- 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2,6-dimethyl-3-isopropyl-5-(methoxy ethyl) pyridine dicarboxylate,
- 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2,6-dimethyl-3-ethyl-5-(methoxy ethyl) pyridine dicarboxylate,
- 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2,6-dimethyl-3-ethyl-5-(methoxy ethyl) pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2-(2′-amino ethoxy) methyl-6-methyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2-(2′-amino ethoxy) methyl-6-methyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2-(2′-amino ethoxy) methyl-6-methyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2-(2′-amino ethoxy) methyl-6-methyl-3,5-pyridine dicarboxylate,
- dimethyl -1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2-(2′-amino ethoxy) methyl-6-methyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2-(2′-amino ethoxy) methyl-6-methyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2-((2′-amino ethoxy) methyl-6-methyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2-(2′-amino ethoxy) methyl-6-methyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2-(2′-amino ethoxy) methyl-6-methyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-ethoxy-3′,5′-dinitro-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-ethoxy-3′,5′-dinitro-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-ethoxy-3′,5′-dinitro-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-methoxy-3′,5′-dinitro-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-methoxy-3′,5′-dinitro-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-methoxy-3′,5′-dinitro-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-isopropoxy-3′,5′-dinitro-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-isopropoxy-3′,5′-dinitro-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-isopropoxy-3′,5′-dinitro-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-ethoxy-3′,5′-diamino-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-ethoxy-3′,5′-diamino-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-ethoxy-3′,5′-diamino-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-methoxy-3′,5′-diamino-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-methoxy-3′,5′-diamino-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-methoxy-3′,5′-diamino-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-isopropoxy-3′,5′-diamino-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-isopropoxy-3′,5′-diamino-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-isopropoxy-3′,5′-diamino-6′-pentadecylphenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2-methyl-6-(5″-methyl-2-mercapto-1′H-benzimidazolyl)methyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2-methyl-6-(5″-methyl-2-mercapto-1′H-benzimidazolyl)methyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-ethoxy-6′-pentadecylphenyl)-2-methyl-6-(5″-methyl-2-mercapto-1′H-benzimidazolyl)methyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2-methyl-6-(5″-methyl-2-mercapto-1′H-benzimidazolyl)methyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2-methyl-6-(5″-methyl-2-mercapto-1′H-benzimidazolyl)methyl-3,5-pyridine dicarboxylate,
- diisopropyl 1,4-dihydro-4-(2′-methoxy-6′-pentadecylphenyl)-2-methyl-6-(5″-methyl-2-mercapto-1′H-benzimidazolyl)methyl-3,5-pyridine dicarboxylate,
- diethyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2-methyl-6-(5″-methyl-2-mercapto-1′H-benzimidazolyl)methyl-3,5-pyridine dicarboxylate,
- dimethyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2-methyl-6-methyl (5′-methyl-2-mercapto-1′H-benzimidazolyl)methyl-3,5-pyridine dicarboxylate, and
- diisopropyl 1,4-dihydro-4-(2′-isopropoxy-6′-pentadecylphenyl)-2-methyl-6-methyl (5′-methyl-2-mercapto-1′H-benzimidazolyl)methyl-3,5-pyridine dicarboxylate.
55 more elements
A compound selected from the group consisting of DHP-1 through DHP-655, DHP-1-11 through DHP-326-11, DHP-653-11 through DHP-655-11, DHP-1-12 through DHP-326-12, DHP-653-12 through DHP-655-12, DHP-1-13 through DHP-326-13, DHP-653-13 through DHP-655-13, DHP-1-14 through DHP-326-14, and DHP-653-14 through DHP-655-14.
Dependencies are inferred from the claim text.