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 psi[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 muM, respectively. In contrast to earlier reported fluoroolefin containing inhibitors, the nitriles underwent no detectable degradation at pH 7.6 under buffered conditions. (C) 2002 Elsevier Science Ltd. All rights reserved.