Novel carbonic anhydrase isozymes I, II and IV activators incorporating sulfonyl-histamino moieties

Sulfonylamido(ureido) derivatives of histamine were synthesized by an origi nal procedure in order to obtain tight-binding activators of the zinc enzym e carbonic anhydrase (CA), exploiting the binding energy of the alkyl/aryls ulfonyl moieties with amino acid residues at the entrance of the active sit e. In contrast to the lead molecule, histamine, the new derivatives possess ed higher affinity for three different CA isozymes, as evidenced by compair ing the affinity constants of these compounds for isozyme CA II. (C) 1999 E lsevier Science Ltd. All rights reserved.