This manuscript reports the identification of a novel series of mono- and bis- benzene sulphonamides with potent binding affinity for bovine carbonic anhydrase II (bCAII). These compounds exhibited nanomolar equilibrium dissociation constants with Ki's ranging from 4.7 to 9.3 nM. All compounds were ester derivatives of the weak affinity bCAII inhibitor, 4-carboxybenzenesulphonamide. Structure-activity relationships for this novel series of compounds are discussed.