P3 SAR exploration of biphenyl carbamate based Legumain inhibitors

Bioorg Med Chem Lett. 2014 Jun 1;24(11):2521-4. doi: 10.1016/j.bmcl.2014.04.002. Epub 2014 Apr 12.

Abstract

This Letter describes the further development and SAR exploration of a novel series of Legumain inhibitors. Based upon a previously identified Legumain inhibitor from our group, we explored the SAR of the carbamate phenyl ring system to probe the P3 pocket of the enzyme. This led to the identification of a sub-nanomolar inhibitor of Legumain.

Keywords: Cancer; Cyano warhead; Legumain; Protease inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology*
  • Carbamates / chemical synthesis
  • Carbamates / chemistry
  • Carbamates / pharmacology*
  • Cysteine Endopeptidases / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Biphenyl Compounds
  • Carbamates
  • Enzyme Inhibitors
  • biphenyl
  • Cysteine Endopeptidases
  • asparaginylendopeptidase