Long-acting dihydropyridine calcium antagonists. 9. Structure activity relationships around amlodipine

Article abstract of DOI:10.1016/0223-5234(91)90132-7

The preparation of a range of 1,4-dihydropyridine analogues of amlodipine has been undertaken and their calcium antagonist activities on rat aorta have been evaluated.Increasing the size of the C5 ester group dramatically reduces calcium antagonist activity, a trend which would be compatible with the carbonyl group of that ester binding to the DHP receptor.Amlodipine analogues with extended C3 ester substituents also have lower potency than amlodipine, possibly because of disruption of a favourable interaction between the protonated amino group on the 2-substituentand the DHP receptor.Replacement of the 6-methyl substituent in amlodipine by alkoxyalkyl groups or electron-withdrawing groups is also detrimental to calcium antagonist activity. amlodipine / 1,4-dihydropyridine / structure activity relationship