Quantitative structure-activity relationship study of recently synthesized 1,4-dihydropyridine calcium channel antagonists. Application of the Hansch analysis method

The Hansch analysis method was applied to a series of recently synthesized nifedipine analogues containing nitroimidazolyl, phenylimidazolyl, and methylsulphonylimidazolyl groups at the C-4 position and different ester substituents at C-3 and C-5 positions of the dihydropyridine ring. Hydrophobic, electronic, inductive, and resonance substituent constants were used. The effect of these parameters on the biological activity of 1,4-dihydropyridines (calcium channel antagonist activity in Guinea-pig ileal cells, 109(1/IC50)) was determined by multiple linear regression analysis. Linear and quadratic relationships were obtained between the activity and these parameters. It was found that both electronic and hydrophobic interactions occur between the nifedipine analogues and the receptor.