Crystal structure of the dihydropyridine calcium antagonist felodipine. Dihydropyridine binding prerequisites assessed from crystallographic data

Abstract

The molecular structure of the dihydropyridine Ca2+ antagonist felodipine (ethyl methyl 1,4-dihydro-2,6 dimethyl-4-(2,3-dichlorophenyl)-3-5-pyridinedicarboxylate) has been determined by X-ray crystallographic methods. The dihydropyridine ring in this potent smooth muscle relaxant is among the flattest found in such structures. This is a qualitive agreement with previous investigations of dihydropyridine Ca2+ antagonists; deviations from planarity in the dihydropyridien ring are generally smallest in the most active compounds. Hydrogen-bonding patterns observed in the crystal lattices of several dihydropyridine Ca2+ antagonists are compared. Antiperiplanar carbonyl groups are partly shielded from forming hydrogen bonds in compounds with relatively bulky ortho phenyl substituents. Conformational prerequistes for a favorable hydrogen-bonding geometry toward a receptor site may thus involve synperiplanar carbonyl groups.