Correlation of activity of 2-(X-benzyloxy)-4,6-dimethoxyacetophenones with topological indices and with the Hansch equation.

The antispasmodic activities of the 2-(X-benzyloxy)-4,6-dimethoxyacetophenones (X = H, 4'-F, 4'-NO2, 4'-CH3, 4'-Cl, 3',4'-(CH3)2, 4'-OCH3, 4'-Br, 4'-C(CH3)3, 4'-OCH2C6H5) against acetylcholine-induced contraction of the guinea pig ileum were correlated with different topological indices. Good correlations were obtained through a simple regression equation with electrotopological state indices (Si) for the carbon atoms S(C1) and S(C6). Using multiple linear regression with two variables the best correlations were obtained with carbons in the 6- and 1-positions with sigma. Such results indicate that the corresponding carbon atoms play an important role in the biological activity. The equation of Hansch showed that the activity of these compounds increases when the ring substituent in the benzyloxy group are more highly electron-releasing and hydrophobic.