Synthesis and enzymatic evaluation of novel partially fluorinated thiol dual ACE/NEP inhibitors

Francesca Olimpieri, Simone Tambaro, Santos Fustero, Paolo Lazzari, Maria Sanchez-Roselló, Luca Pani, Alessandro Volonterio, Matteo Zanda

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7 Citations (Scopus)

Abstract

A novel family of peptidomimetics incorporating fluoroalkyl groups, mainly a trifluoromethyl, in alpha-position to a zinc(II)-binding thiol function, was synthesized in solution as well as in solid-phase. These compounds showed inhibitory potency in the nanomolar range against both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), whereas no inhibition of endothelin-converting enzyme-1 (ECE-1) was observed. The trifluoromethyl-derivatives were more potent than the parent unfluorinated analogues in the case of ACE, and less potent in the case of NEP.
Original languageEnglish
Pages (from-to)4715-4719
Number of pages5
JournalBioorganic & Medicinal Chemistry Letters
Volume19
Issue number16
Early online date21 Jun 2009
DOIs
Publication statusPublished - 15 Aug 2009

Keywords

  • angiotensin-converting enzyme inhibitors
  • fluorine
  • humans
  • neprilysin
  • peptides
  • peptidyl-dipeptidase A
  • protease inhibitors
  • sulfhydryl compounds

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    Olimpieri, F., Tambaro, S., Fustero, S., Lazzari, P., Sanchez-Roselló, M., Pani, L., Volonterio, A., & Zanda, M. (2009). Synthesis and enzymatic evaluation of novel partially fluorinated thiol dual ACE/NEP inhibitors. Bioorganic & Medicinal Chemistry Letters, 19(16), 4715-4719. https://doi.org/10.1016/j.bmcl.2009.06.064