Thrombin inhibitors. 3. Carboxyl-containing amide derivatives of N alpha-substituted L-arginine.
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 thrombin. The most inhibitory compounds were obtained when a carboxyl group was introduced into the carbon next to the amide nitrogen of N alpha-(arylsulfonyl)-L-arginine amide derivatives, e.g., N alpha-(arylsulfonyl)-L-arginyl-N-butyl-, N-(methoxyethyl)- or N-(tetrahydrofurfuryl)glycine and 4-alkyl-1-[N alpha-(arylsulfonyl)-L-arginyl]-2-piperidinecarboxylic acid, with an I50 of 1-3 X 10(-7) M.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000517:prevention & control
D001120:Arginine; D013917:Thrombin