CARBONIC-ANHYDRASE INHIBITORS .24. A QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF POSITIVELY CHARGED SULFONAMIDE INHIBITORS

A quantitative structure-activity relationship (QSAR) study is presented for 28 carbonic anhydrase inhibitors (CAIs), derivatives of tri-, tetra- and penta-substituted 1-(2-sulfonamido-1,3,4-thiadiazol-5-yl)pyridinium perchlorates. Several of these derivatives are new compounds and their synthesis and properties are also reported. The conclusion of the study is that activity is greatly modulated by electronic effects on the pyridinium ring. The most significant effects were enhancement of activity with increased positive charge on this ring, weakening of activity with increasing HOMO energy, and a dependence on anisotropic polarizability which may be attributable to London forces.