Title : Synthesis, vasodilator and calcium channel blocking activity of a new class of 1,4-dihydropyridines
In the search for new therapeutics for the treatment of some cardiovascular diseases, some new 1,4-dihydropyridines bearing sulfonylurea, urea and thiourea moieties were synthesized and pharmacologically evaluated for their vasodilator activity, comparatively to nifedipine and diazoxide. The investigations of the target compounds on rat aorta rings showed that, except for the sulfonylureas derivatives, which were inactive ( EC50 > 100 μΜ), ureas and thioureas derivatives showed moderate to strong vasodilator activity, with EC50 values varying from 1.2 to 40 μM. 17-fold more active than diazoxide (but less active than nifedipine), the most active compound (1.2 ± 0.2 μM) was found to be a voltage-gated calcium channels blocker, as it is the case for the reference compound, nifedipine. The results also showed that an aliphatic or aromatic R group (the latter bearing electron-donating or electro-withdrawing substituents) gave very active compounds. The inactiveness of sulfonylurea derivatives could be explained by a partial ionization at physiological pH because of their weak acid character.