Abstract
Thrombotic disorders represent the major share of the various cardiovascular diseases, and significant progress has been made in the development of synthetic thrombin inhibitors as new anticoagulants. In addition to the development of highly potent and selective inhibitors with improved safety and suitable half-life, several allosteric inhibitors have been designed and synthesized, that did not fully nullify the procoagulant signal and thus could result in reduced bleeding complications. Furthermore, natural products with thrombin inhibitory activity have been isolated, and some natural products have been modified in order to improve their inhibitory activity and metabolic stability. This review summarizes the development of orally active thrombin inhibitors for the treatment of thrombotic disorder diseases, which could serve as a reference for the interested researchers.
Highlights
Thrombotic disorders, which are resulted from abnormalities in the blood flow, coagulation cascade or fibrinolysis, can lead to deep vein thrombosis, myocardial infarctions and strokes
This review focuses on the development of orally active thrombin inhibitors for treating thrombotic disorders since 2010, and could serve as an updated reference for interested researchers
This compound selectively inhibited the thrombin with its Ki value was 0.77 nm (Ki = 483 mM for trypsin, about 627 million-fold), its activity in the 2 × activated partial thromboplastin time (APTT) assay (2 × APTT = 0.38 μM) was significantly improved
Summary
Thrombotic disorders, which are resulted from abnormalities in the blood flow, coagulation cascade or fibrinolysis, can lead to deep vein thrombosis, myocardial infarctions and strokes. Warfarin is an oral antithrombotic agent, it possesses a number of limitations [2] including an indirect action mechanism, the need for constant monitoring to assure effective drug plasma levels and avoidance of bleeding complications, and potential drug–drug interactions. Other antithrombotics such as heparin and low-molecular-weight heparin, must be given parenterally because they lack oral bioavailability, which is a major obstacle for the chronic treatment of thromboembolic diseases [3]. This review focuses on the development of orally active thrombin inhibitors for treating thrombotic disorders since 2010, and could serve as an updated reference for interested researchers
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