Cyclic amides of N alpha-arylsulfonylaminoacylated 4-amidinophenylalanine--tight binding inhibitors of thrombin.
Variation of the potent thrombin inhibitors derived from N alpha-arylsulfonyl-4-amidinophenylalanine was carried out by interposition of an omega-aminoalkylcarboxylic acid between the N alpha-arylsulfonyl residue and the 4-amidinophenylalanine part. The use of glycine as spacer renders the compounds tight binding inhibitors of thrombin. The Ki of the most potent inhibitor reaches the nmol/l range. The inhibitory effect is specifically directed against thrombin, the Ki values for inhibition of trypsin, plasmin and factor Xa are some orders of magnitude higher than those for thrombin inhibition.
D000818:Animals; D001667:Binding, Competitive; D001777:Blood Coagulation / Q000187:drug effects*; D002417:Cattle; D005340:Fibrinogen / Q000502:physiology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*
D010649:Phenylalanine; D005340:Fibrinogen; D013917:Thrombin