Identification and Optimization of Novel Antithrombotic Agents

Anticoagulants have been routinely prescribed to patients for the treatment of blood clots for over half a century, however these current therapies are prone to drug-drug and food-drug interactions, major bleeding risks, and toxicity issues. *undisclosed target* is a protease involved in coagulation and currently there are no small molecule modulators against this target available on market. Studies have shown that the inhibition of *undisclosed target* can halt coagulation with the added benefit of minimal bleeding risks, based on in vivo data from *undisclosed target* and genetic *undisclosed target* deficiency. Herein efforts are described surrounding the design and evaluation of small molecule modulators of *undisclosed target*, beginning with the identification of two hit compounds, following a HTS campaign. The more potent hit was taken forwards for the generation of SAR, comprising of computational modelling, synthetic chemistry, and in vitro testing. Finally, a fragment-based approach was then established to identify a new series of potential *undisclosed target* inhibitors. This method combined computational modelling and NMR spectroscopy-based experiments.