Thrombin inhibitors. 1. Ester derivatives of N.alpha.-(arylsulfonyl)-L-arginine

Abstract

A series of N.alpha.-(arylsulfonyl)-L-arginine esters was prepared and tested as inhibitors of the clotting activity of animal thrombin. N.alpha.-Dansyl-L-arginine methyl ester was the most inhibitory of the N.alpha.-(arylsulfonyl)-L-arginine methyl esters. The most potent inhibitors were the n-propyl and n-butyl esters of N.alpha.-dansyl-L-arginine with an I50 [median inhibitory concentration] of 2 .times. 10-6 M. Esters of unsaturated straight-chain alcohols with a chain length of 4 C were as inhibitory as the n-butyl ester. The inhibitors were hydrolyzed by thrombin and trypsin more slowly than N.alpha.-tosyl-L-arginine methyl ester.