Novel synthesis and pharmacological evaluation as α2-adrenoceptor ligands of O-phenylisouronium salts

The synthesis of nine new mono- and bis-O-phenylisouronium compounds ( 2, 6b-10b and 12b-14b) and their Boc-protected isourea precursors (2a, 6a-10a and 12a-14a) is described. The carbodiimide 4, which was formed, had been suggested as the reactive intermediate species and driving force of the reaction. All final substrates were tested as potential alpha(2)-ARs ligands in human brain tissue by means of radioligand binding experiments and were compared to the potential antidepressant 1, as well as other related guanidine containing derivatives. (C) 2008 Elsevier Ltd. All rights reserved.