QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS FOR 1,4-DIHYDROPYRIDINECALCIUM-CHANNEL ANTAGONISTS (NIFEDIPINE ANALOGS) - A QUANTUM CHEMICALCLASSICAL APPROACH/

A quantum chemical (AM1) combined with a classical study of structure- activity relationships for 1,4-dihydropyridines (nifedipine analogues) was performed. The biological data were taken from the literature. Th e quantum chemical parameters tested were energies of HOMO and LUMO, d ipole moment (total and partial), hardness, Mulliken electronegativity , frontier orbital indices, and others. Also tested were classical par ameters like Hansch hydrophobic constant, pi; Hammett electronic const ant for the mete position, sigma(m); and the Verloop sterimol paramete rs, B-1 and L. The van der Waals volume was also tested. The pharmacol ogical activities of the para monoderivatives are negatively correlate d with the molecular volume, i.e. a steric factor. The meta position o f the phenyl ring is affected by steric and electronic parameters, whe reas the ortho position seems to be affected by hydrophobic and electr onic parameters.