Design, Synthesis and Biological Actmty of Novel Rigid Amidino-Phenylalanine Derivatives as Inhibitors of Thrombin

Abstract
(3S)-(Naphthalene-2-sulfonylamino)-1-[2R-(4-amidinophenyl)-1-piperidinocarbonylethyl]-2-pyrroli-dinone (1a) is a potent inhibitor of thrombin with an IC50 value by 112 times lower than that of NAPAF’ (racemate). The selectivity versus trypsin can be improved by incorporation of substituents on the naphthyl ring. The mode of binding of the compound was determined by X-ray crystallography.