Industrial Drug Research: Development of Ca‐Antagonistic Vasodilators

Abstract The prime aim of industrial drug research is the development of new therapeutics; correspondingly it has to consider not only drug‐receptor interaction, but also such important aspects as pharmacokinetics, side effects and toxicology. An example for this complex pattern of industrial drug research is given here for the development of the dihydropyridine‐like Ca‐antagonist felodipine. Several felodipine analogues with different ester groups in 3‐ and 5‐position of the dihydropyridine ring were synthesized and their biological activities evaluated in screening procedures. Both in vitro and in vivo potency was determined, as well as selectivity for vascular smooth muscle, in comparison to cardiac muscle. Structure‐activity relationships were studied in a group of these dihydropyridine esters (DHP‐esters) to ensure that the compound selected for further biological evaluation (felodipine) is close to the optimum as far as the screening parameters are concerned. In the second part of the paper pharmacokinetic properties and clinical profile of felodipine are summarized.