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Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors
Published on: November 23, 2019
Irreversible inhibition of dipeptidyl peptidase 8 by dipeptide-derived diaryl phosphonates
Pieter Van der Veken1, Anna Soroka, Inger Brandt
1Laboratory of Medicinal Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. pieter.vanderveken@ua.ac.be
Abstract:
Dipeptide-derived compounds, bearing various P2 residues and a diaryl pyrrolidin-2-yl phosphonate at the P1 position, were evaluated as dipeptidyl peptidase 8 (DPP8) inhibitors. With these products, irreversible inhibition of DPP8 was observed. To obtain inhibitors with an improved activity and selectivity profile, a set of selected analogues containing a diaryl isoindolin-1-ylphosphonate at P1 was synthesized and evaluated. Within this latter series, compound 2e was shown to be a potent, irreversible inhibitor of DPP8, demonstrating very low affinity for DPP IV and DPP II.
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