The structure-activity relationships (SAR) of six-membered ring replacements for the imidazole ring scaffold is described. This work led to the discovery of the potent and selective pyridine (S)-23 and pyridinone (±)-24 factor XIa inhibitors. SAR and X-ray crystal structure data highlight the key differences between imidazole and six-membered ring analogs.
Keywords: Activated partial thromboplastin time; FXIa; Factor XIa inhibitors; Thrombosis; aPTT.
Copyright © 2014 Elsevier Ltd. All rights reserved.