Identification and SAR exploration of a novel series of Legumain inhibitors

Bioorg Med Chem Lett. 2019 Jun 15;29(12):1546-1548. doi: 10.1016/j.bmcl.2019.03.019. Epub 2019 Mar 29.

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.

Keywords: Legumain; SAR; Small molecule inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Humans
  • Mice
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Cysteine Proteinase Inhibitors
  • Cysteine Endopeptidases
  • asparaginylendopeptidase