Thrombin inhibitors. 1. Ester derivatives of N alpha-(arylsulfonyl)-L-arginine.
A series of N alpha-(arylsulfonyl)-L-arginine esters was prepared and tested as inhibitors of the clotting activity of 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 of 2 X 10(-6) M. Esters of unsaturated straight-chain alcohols with a chain length of four carbons were also 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.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D002417:Cattle; D004951:Esterification; D006868:Hydrolysis; D066298:In Vitro Techniques; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D001120:Arginine; D014357:Trypsin; D013917:Thrombin