AbstractThe inhibition of Bovine Carbonic Anhydrase B (BCA‐B) by an appropriately designed set of meta‐ and para‐substituted benzenesulfonamides was studied. From the results the following quantitative structure‐activity relationship was derived: log 1/Ki = 0.95 σ + 0.54 π – 0.35 B5,3+ 6.29. In this equation Ki is the inhibition constant, σ is the Hammett constant, π is the hydrophobic parameter and B5,3is the sterimol steric parameter for the meta substituents. Using this equation we designed, synthesized and successfully predicted Ki for a new congener intended to maximize the inhibitory potency (1/Ki). The interactions involved in the enzyme‐inhibitors binding as suggested by the correlation equation, have been tentatively interpreted using computer built 3‐D molecular models based on the published X‐ray crystallographic coordinates of the free and inhibitor‐bound carbonic anhydrase. The results from our analyses have been compared with those obtained in some p