Synthesis and selective vasodilating properties of esters of 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-dihydro-pyridine-3,5-di- carboxylic acid

This study presents the synthesis of new 1,4-dihydropyridine (DHP) derivatives which are phenoxy- and alkoxyalkyl esters of 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-dihydropyridine-3,5-dica rbo xylic acid and reports on the biological activity of the compounds. It was found that the DHP derivati...

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Published inArzneimittel-Forschung Vol. 39; no. 10; p. 1185
Main Authors Dubur, G J, Veveris, M M, Weinheimer, G, Bisenieks, E A, Makarova, N R, Kimenis, A A, Uldrikis, J R, Lukevics, E J, Dooley, D, Osswald, H
Format Journal Article
LanguageEnglish
Published Germany 01.10.1989
Subjects
Animals
Calcium - pharmacology
Cats
Cerebral Cortex - metabolism
Chemical Phenomena
Chemistry
Dihydropyridines - chemical synthesis
Dihydropyridines - pharmacology
Dogs
Esters - chemical synthesis
Esters - pharmacology
Guinea Pigs
In Vitro Techniques
Isradipine
Male
Muscle Contraction - drug effects
Muscle, Smooth, Vascular - drug effects
Myocardial Contraction - drug effects
Papillary Muscles - drug effects
Potassium - pharmacology
Pyridines - metabolism
Rabbits
Rats
Rats, Inbred Strains
Vasodilator Agents - chemical synthesis
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Summary:This study presents the synthesis of new 1,4-dihydropyridine (DHP) derivatives which are phenoxy- and alkoxyalkyl esters of 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-dihydropyridine-3,5-dica rbo xylic acid and reports on the biological activity of the compounds. It was found that the DHP derivatives showed high affinity to the DHP receptor of rat brain membranes and antagonize potently the potassium depolarization-induced vasospasm in a fashion compatible with the assumption of a calcium entry blockade. The higher vasodilating potency of especially compound III for the cerebral vasculature might represent an improved selectivity profile due to specific substitution patterns of the DHP molecule by increasing lipophilicity. Thus, the new DHP derivatives might be useful as therapeutic agents for hypertension and impaired cerebral microcirculation.
ISSN:0004-4172