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

A novel family of peptidomimetics incorporating fluoroalkyl groups, mainly a trifluoromethyl, in α-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.

A series of novel peptidomimetics incorporating fluoroalkyl groups have been synthesized in solution and in solid phase. These compounds were found to be dual ACE/NEP inhibitors in the nanomolar range.Figure optionsDownload as PowerPoint slide