Force field and semiempirical MO conformational analysis of dihydropyridine calcium-channel antagonists

Force field and semiempirical MO calculations were used to investigate the conformational features (dihydropyridine ring puckering, inter-ring and sid e-chain dihedral angles) of a group of 4-aryl substituted dihydropyridine c alcium-channel antagonists. The considered compounds were studied both in v acuo and in water (simulated with the Cosmo approach). For derivatives bear ing a basic side chain the corresponding protonated structures were also su bmitted to MO calculations. The investigation highlighted the conformationa l flexibility of the dihydropyridine derivatives, the Delta H-f of the most stable uncharged conformers of each compound lying in a range of 2-7 kcal. mol(-1). (C) 1999 Elsevier Science B.V. All rights reserved.