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

The antispasmodic activities of the 2-(X-benzyloxy)-4,6-dimethoxyacetopheno nes (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 gu inea pig ileum were correlated with different topological indices. Good cor relations were obtained through a simple regression equation with electroto pological state indices (S-i) for the carbon atoms S(C-1) and S(C-6). Using multiple linear regression with two variables the best correlations were o btained with carbons in the 6- and 1-positions with sigma. Such results ind icate that the corresponding carbon atoms play an important role in the bio logical activity. The equation of Hansch showed that the activity of these compounds increases when the ring substituent in the benzyloxy group are mo re highly electron-releasing and hydrophobic. (C) 1999 Elsevier Science S.A . All rights reserved.