Updates on Intrinsic Medicinal Chemistry of 1,4-dihydropyridines, Perspectives on Synthesis and Pharmacokinetics of Novel 1,4-dihydropyrimidines as Calcium Channel Blockers: Clinical Pharmacology

Several chemical studies described the physiological efficacy of 1,4- dihydropyridines (DHPs). DHPs bind to specific sites on the α1 subunit of L-type calcium channels, where they demonstrate a more pronounced inhibition of Ca2+ influx in vascular smooth muscle compared to myocardial tissue. This selective inhibition is the basis for their preferential vasodilatory action on peripheral and coronary arteries, a characteristic that underlies their therapeutic utility in managing hypertension and angina. Among the vascular-selective DHPs, nifedipine, felodipine, and isradipine are key representatives, with nifedipine often considered the archetype due to its widespread use and efficacy in promoting vascular relaxation. Significant efforts have been made to modify the structure of nifedipine, the prototype of DHPs to better understand structure-activity relationships (SARs) and amplify calcium-modulating effects.