Macrocyclic factor XIa inhibitors. Issue 17 (1st September 2017)

• Record Type: Journal Article
• Authors: Wang, Cailan; Corte, James R.; Rossi, Karen A.; Bozarth, Jeffrey M.; Wu, Yiming; Sheriff, Steven; Myers, Joseph E.; Luettgen, Joseph M.; Seiffert, Dietmar A.; Wexler, Ruth R.; Quan, Mimi L.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 17(2017)
• Page Start: 4056
• Page End: 4060
• Publication Date: 2017-09-01
• Subjects: Factor XIa inhibitors -- FXIa -- Activated partial thromboplastin time -- aPTT -- Thrombosis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.07.048
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an analysis of the crystal structures of the acyclic phenylimidazole compounds. Further optimization using structure-based design led to inhibitors with pM affinity for FXIa, excellent selectivity against a panel of relevant serine proteases, and good potency in the activated partial thromboplastin time (aPTT) clotting assay.