Structure-activity relationships for the inhibition of acrosin by benzamidine derivatives

Abstract

A series consisting of 52 benzamidine derivatives, was evaluated for inhibitory activity against homogeneous boar sperm acrosin [EC 3.4.21.10]. All of the compounds in the series proved more potent than benzamidine (Ki [inhibition constant] = 4.0 .times. 10-6 M), with 1 of the derivatives, .alpha.-(4-amidino-2,6-diiodophenoxy)-3-nitrotoluene showing outstanding potency with a Ki value of 4.5 .times. 10-8 M. Although all of the derivatives were effective acrosin inhibitors, structural specificity was observed within homologous groups of compounds. The information gained from this preliminary study should prove extremely beneficial in the design and synthesis of future acrosin inhibitors. [Acrosin inhibition possesses a powerful potential to serve an antienzymatic approach to fertility control].