X-ray crystallographic and theoretical studies of substituted phenyl 3,5-di[N-methyl] carbamoyl-1,4-dihydropyridines:: Targets for Ca2+ antagonist

A series of 4(x-substituted phenyl)-1,4-dihydropyridines (x = 2-CF3 (1), 2-CH3 (2), 2-OCH3 (3) and 2,4-Cl (4)) with a new substituent, the N-methylcarbamoyl (CONHCH3) group at C3 and C5 are crystallographically characterized and a comparison has been made with important conformational parameters obtained theoretically. The dihydropyridine rings are in shallow boat conformation. The phenyl substituent orientation is synperiplanar. Both the carbonyl groups are oriented anticlinal in 1, 2 and 3; but in 4, one is synclinal and the other synperiplanar with the adjacent double bond. The presence of solvent molecules in 1 (CH3OH), 2 (CH3OH), and 3 (H2O) has significantly changed the hydrogen bonding pattern. Theoretical studies;at the semiempirical AM1 MO level reproduces the general features of the structures. The near planarity of the DHP ring and the orientation of the phenyl substituent make 1 and 2 encouraging targets for pharmacological, study. Crystallographic Data:1: a = 8.793(2), b = 29.962(5), c = 8.215(2) Angstrom, beta = 115.28(2)degrees, Monoclinic, P2(1)/c; 2: a = 8.799(2), b = 15.789(3), c = 14.074(2) Angstrom, beta = 100.25(2)degrees, Monoclinic, P2(1)/n; 3: a = 8.347(1), b = 8.986(1), c = 13.749(2) Angstrom, alpha = 97.50(1), beta = 94.78(1), gamma = 101.38(1)degrees Triclinic, <P(1)over bar>4: a = 12.928(3), b = 14.506(3), c = 9.740(2) Angstrom, Orthorhombic, Pca2(1).