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-methylcar bamoyl (CONHCH3) group at C3 and C5 are crystallographically characterized and a comparison has been made with important conformational parameters obt ained theoretically. The dihydropyridine rings are in shallow boat conforma tion. The phenyl substituent orientation is synperiplanar. Both the carbony l 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 ch anged the hydrogen bonding pattern. Theoretical studies;at the semiempirica l AM1 MO level reproduces the general features of the structures. The near planarity of the DHP ring and the orientation of the phenyl substituent mak e 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), ga mma = 101.38(1)degrees Triclinic, <P(1)over bar>4: a = 12.928(3), b = 14.50 6(3), c = 9.740(2) Angstrom, Orthorhombic, Pca2(1).