Fig. 4: Sulphostin-inspired N-phosphono-(S)−3-aminopiperidine-2-ones inhibit DPPs.
From: Sulphostin-inspired N-phosphonopiperidones as selective covalent DPP8 and DPP9 inhibitors
a Chemical structure of Sulphostin-inspired N-phosphono-(S)−3-aminopiperidine-2-ones. The previously identified leaving group is shown in purple. b Representative synthesis route of N-phosphono-(S)−3-aminopiperidine-2-ones by activation of a phosphonate diethyl ester 2 with oxalyl chloride yielding a chloro-phosphonate intermediate 3, which then reacts with in situ lithiated Alloc-protected (S)−3-aminopiperidine-2-one 4 resulting in corresponding N-phosphono-(S)−3-aminopiperidine-2-one 5. c Kinetic analysis of DPP inhibition by N-phosphono-(S)−3-aminopiperidine-2-ones. The pseudo-first order rate constant (kobs) was calculated from an exponential regression of progress curves and plotted against the inhibitor concentration. KI and kinact were obtained via fitting to a hyperbolic equation. All activity measurements were performed in triplicate (n = 3 technical replicates), mean values are shown and error bars indicate the SEM. Source data are provided as a Source Data file.
