Inhibition of dipeptidyl peptidase IV (DPP IV) by 2-(2-amino-1-fluoro-propylidene)-cyclopentanecarbonitrile, a fluoroolefin containing peptidomimetic

Novel, potent inhibitors of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5, CD26), containing the fluoroolefin peptide isostere ψ [CFC], have been prepared via the intermediacy of the Peterson fluoroolefination reaction. The nitrile containing inhibitors were found to inhibit dipeptidyl peptidase IV competitively with K i values for the l- 3 and u- 3 inhibitors of 7.69 and 6.03 μM, respectively. In contrast to earlier reported fluoroolefin containing inhibitors, the nitriles underwent no detectable degradation at pH 7.6 under buffered conditions. Graphic