Identification and SAR exploration of a novel series of Legumain inhibitors. Issue 12 (15th June 2019)

• Record Type: Journal Article
• Authors: Eddie, Sharon L.; Gregson, Aaron; Graham, Emma; Burton, Stephanie; Harrison, Timothy; Burden, Roberta; Scott, Christopher J.; Mullan, Paul B.; Williams, Rich
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 12(2019)
• Page Start: 1546
• Page End: 1548
• Publication Date: 2019-06-15
• Subjects: Legumain -- Small molecule inhibitor -- SAR; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.03.019
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: This letter describes the development of a series of potent and selective small molecule Legumain inhibitors suitable as chemical probes for in vitro experiments. Our previous research had identified a dipeptide inhibitor utilizing a semi-reversible cyano warhead that generated 2, a cell active inhibitor. This work explores an alternative P2-P3 linker and further SAR exploration of the P3 group which led to the identification of 16i, a highly potent inhibitor with excellent physiochemical properties.