Ac. Gaudio et al., QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS FOR 1,4-DIHYDROPYRIDINECALCIUM-CHANNEL ANTAGONISTS (NIFEDIPINE ANALOGS) - A QUANTUM CHEMICALCLASSICAL APPROACH/, Journal of pharmaceutical sciences, 83(8), 1994, pp. 1110-1115
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.