A quantitative structure-activity relationship and molecular graphics study of carbonic anhydrase inhibitors

C Hansch, J McClarin, T Klein and R Langridge

A quantitative structure-activity relationship (QSAR) (log K = 1.55 alpha + 0.64 log P - 2.07I1 - 3.28I2 + 6.94) has been formulated for the binding of a set of substituted benzenesulfonamides to human carbonic anhydrase. The binding constant (K) are from the studies of King and Burgen [Proc. R. Soc. Lond. B. 193:107-125 (1976)], sigma is the Hammett electronic substituent constant, P is the octanol/water partition coefficient, and I1 and I2 are indicator variables for meta and ortho substituents, respectively. The negative coefficients with the indicator variables suggest steric hindrance by these substituents in contrast to para substituents. Qualitative features of the QSAR are correlated with a color stereomolecular graphics model of the enzyme- inhibitor complex which was constructed from the X-ray crystallographic coordinates of the enzyme.

Volume 27, Issue 5, pp. 493-498, 05/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics