Carbonic anhydrase inhibitors. Part 86. A QSAR study on some sulfonamide drugs which lower intra-ocular pressure, using the ACE non-linear statistical method

Quantum chemical QSAR expressions have been developed for a heterogeneous group of 36 sulfonamides which have been shown to lower intraocular pressure in in vivo tests on animals. It was found, using the ACE statistical technique, that the lowering of intraocular pressure correlated non-linearly with K-I for carbonic anhydrase inhibition and with solubility. Non-linear transformations had to be applied to both the response variable and to solubility. Chemical variables found to be relevant to CA inhibition included the dipole moment vector, the frontier orbital energies, the solvation energy determined by the COSMO model, the electrostatic potential based charges on the atoms of the sulfonamide group, and the size and polarizability of the molecule. (C) 2000 Editions scientifiques et medicales Elsevier SAS.