Small-molecule direct thrombin inhibitors: 1997 - 2000

Abstract

Thrombin is a multifunctional enzyme whose properties have been well documented. Because of the importance of this enzyme in the blood coagulation cascade, thrombin has emerged as an attractive target for the treatment and prevention of several cardiovascular disorders. Over the years several strategies have emerged in the search for a small-molecule direct thrombin inhibitor. Research efforts in the field have focused on covalent and non-covalent peptides, as well as peptide surrogates that bind to the active site of the enzyme. Recently, thrombin inhibitors lacking the conventional hydrogen bonding capabilities of the aforementioned subtypes have received an increased amount of attention. This review accounts the patent literature covering these classes of thrombin inhibitors since the last review in 1997.