Thrombin inhibitors. 3. Carboxyl-containing amide derivatives of N.alpha.-substituted L-arginine

Abstract

A series of N.alpha.-(arylsulfonyl)-L-arginine amide derivatives having carboxamide N-substituents with a carboxyl group was prepared and tested as inhibitors of the clotting activity of animal thrombin. The most inhibitory compounds were obtained when a carboxyl group was introduced into the C next to the amide N of N.alpha.-(arylsulfonyl)-L-arginine amide derivatives, e.g., N.alpha.-(arylsulfonyl)-L-arginyl-N-butyl-, N-(methoxyethyl)- or N-(tetra-hydrofurfuryl)glycine and 4-alkyl-1-[N.alpha.-(arylsulfonyl)-L-arginyl]-2-piperidinecarboxylic acid, with an I50 [median inhibitory concentration] of 1-3 .times. 10-7 M.