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.
- angiotensin-converting enzyme inhibitors
- peptidyl-dipeptidase A
- protease inhibitors
- sulfhydryl compounds
Olimpieri, F., Tambaro, S., Fustero, S., Lazzari, P., Sanchez-Roselló, M., Pani, L., ... 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