Carbonic anhydrase inhibitors .41. Quantitative structure-activity correlations involving kinetic rate constants of 20 sulfonamide inhibitors from a non-congeneric series

A quantitative structure-activity relationship study is presented for 20 sulfonamide inhibitors of carbonic anhydrase. These drugs do not form a classical congeneric series, in that the only common factor is the sulfonamide group, which is attached to a variety of substituted aromatic and hetero-aromatic nuclei. The important factors were local factors such as Mulliken charge on atoms of the sulfonamide group, and global factors such as the size and shape of the molecule, its calculated frontier orbital energies, and its lipophilicity. Good correlations were obtained with the equilibrium constant and the kinetic association rate constant, but not with the kinetic dissociation rate constant.