Synthesis and evaluation of new phosphonated δ‐lactam and glutarimide derivatives as angiotensin converting enzyme inhibitors. (11th September 2022)

• Record Type: Journal Article
• Authors: Abdelli, Abderrahmen; Bejaoui, Oumayma; Bougatef, Hajer; Ouni, Sarra; Sila, Assaâd; M'rabet, Hedi; Moreau, Xavier; Efrit, Mohamed Lotfi; Prim, Damien
• Is Part Of: Journal of heterocyclic chemistry. Volume 60:Number 1(2023)
• Page Start: 96
• Page End: 105
• Publication Date: 2022-09-11
• Subjects: Heterocyclic compounds -- Periodicals; 547.59
• DOI: 10.1002/jhet.4566
• Languages: English
• ISSNs: 0022-152X

Abstract

Abstract: An efficient synthesis of new γ, δ‐insaturated δ‐lactam and glutarimide derivatives bearing a phosphonomethyl group from a common allylphosphonate precursor is described. Our approach is based on a two‐step procedure involving the preparation of phosphonated‐1, 5‐ketoester and −1, 5‐diester followed by an amidation–heterocyclization sequence. The first step proceeds via Michael's addition of ethyl acetoacetate and diethyl malonate on an allylphosphonate starting material. The second step consists of a base‐promoted intramolecular amidation‐cyclization sequence with primary amines, which accounts for the construction of δ‐lactams and glutarimide skeletons. We performed the evaluation of angiotensin I‐converting enzyme (ACE) inhibition using an in vitro enzyme assay on six new compounds. Five compounds showed potent ACE inhibitory activity, with IC50 values ranging from 0.02 to 0.27 mg/ml. Compared with Captopril, used as a reference drug, two new glutarimide derivatives exhibited higher efficiency ACE inhibition activity. Abstract : Synthesis and biological evaluation of new phosphonated δ‐lactams and glutarimides.