An update on recent patents on thrombin inhibitors (2010-2013)

作者：Mehta Akul Y; Jin Yingzi; Desai Umesh R^*

来源：Expert Opinion on Therapeutic Patents, 2014, 24(1): 47-67.

DOI：10.1517/13543776.2014.845169

• allosteric inhibition
• anticoagulant
• coagulation enzyme
• drug design
• enzyme inhibition
• thrombosis

Introduction: Thromboembolic incidences have increased nearly 33% in the past decade and directly affect nearly 0.5% of the population. Heparin, warfarin and current direct thrombin inhibitors (DTIs), the primary anticoagulants of choice, suffer from several drawbacks. Thus, the search for an antithrombotic devoid of adverse effect continues in earnest.
Areas covered: Literature search covering PubMed, SciFinder (TM) Scholar, Web of Knowledge, Espacenet, PatentScope and Google Patent Search was used to uncover > 35 patents describing new chemical entities and advances in DTI technologies. Our search uncovered considerable emphasis on the development of larger more complex molecules such as peptide-based inhibitors, prodrug derivatives, bivalent tryptophan zippers, triple action inhibitors and allosteric inhibitors. Advances in formulation technologies for clinically relevant DTIs have also been made.
Expert opinion: Thrombin is a multifaceted, dynamic enzyme with both coagulant and anticoagulant functions. Newer DTIs are attempting to fine tune thrombin's activity by targeting allosteric sites or by site-specific targeting of clotting. The complexity of thrombin's functions is driving the design of complex anticoagulants. Advancements in formulations and production processes have attempted to make traditional DTIs more cost effective to produce. The literature reveals a trend to develop a thrombin 'modulator' rather than an 'inhibitor.'

• 出版日期2014-1