Fluorobenzoyl dipeptidyl derivatives as inhibitors of the Fasciola hepatica cysteine protease cathepsin L1

Mike Moran, F.P. Anderson, D.M. Ruth, C.O. Fagain, John Dalton, P.T.M. Kenny

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Cathepsins are known to have many important physiological roles and provide a viable target for inhibition. Fluorobenzoyl dipeptide derivatives were synthesized and tested for biological activity in an effort to find an efficient inhibitor of the cysteine protease cathepsin L. Thirty-six novel inhibitors (1-36) were synthesized from protected amino acids via the standard DCC/HOBt coupling protocol, containing a benzyl ester or a nitrile as an electrophilic warhead. The activity of the inhibitors was evaluated against cathepsin L and IC50 values calculated. Modification of both amino acids and terminal groups afforded compounds with single digit micromolar inhibition. Results utilizing the benzoyl-L-leucine-glycine nitrile backbone are comparable to that for the commercially available inhibitor 39.
Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume25
Issue number1
DOIs
Publication statusPublished - Feb 2010

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

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