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

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Olimpieri F, Tambaro S, Fustero S, Lazzari P, Sanchez-Rosello M, Pani L, Volonterio A, Zanda M

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

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4715-9. doi: 10.1016/j.bmcl.2009.06.064. Epub 2009 Jun 21.

PubMed ID

19596577 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Captopril	Angiotensin-converting enzyme	IC 50 (nM)	0.12	N/A	N/A	Details