Reversible covalent direct thrombin inhibitors.

ABSTRACT:

Introduction

In recent years, the traditional treatments for thrombotic diseases, heparin and warfarin, are increasingly being replaced by novel oral anticoagulants offering convenient dosing regimens, more predictable anticoagulant responses, and less frequent monitoring. However, these drugs can be contraindicated for some patients and, in particular, their bleeding liability remains high.

Methods

We have developed a new class of direct thrombin inhibitors (VE-DTIs) and have utilized kinetics, biochemical, and X-ray structural studies to characterize the mechanism of action and in vitro pharmacology of an exemplary compound from this class, Compound 1.

Results

We demonstrate that Compound 1, an exemplary VE-DTI, acts through reversible covalent inhibition. Compound

SUBMITTER: Sivaraja M 

PROVIDER: S-EPMC6072017 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature