Small-molecule direct thrombin inhibitors: 1997-2000

Thrombin is a multifunctional enzyme whose properties have been well docume nted. Because of the importance of this enzyme in the blood coagulation cas cade, thrombin has emerged as an attractive target for the treatment and pr evention of several cardiovascular disorders. Over the years several strate gies have emerged in the search for a small-molecule direct thrombin inhibi tor. Research efforts in the field have focused on covalent and non-covalen t peptides, as well as peptide surrogates that bind to the active site of t he enzyme. Recently, thrombin inhibitors lacking the conventional hydrogen bonding capabilities of the aforementioned subtypes have received an increa sed amount of attention. This review accounts the patent literature coverin g these classes of thrombin inhibitors since the last review in 1997.