Fluoro-Olefins as Peptidomimetic Inhibitors of Dipeptidyl Peptidases

The feasibility of the fluoro-olefin function as a peptidomimetic group in inhibitors for dipeptidyl peptidase IV and II (DPP IV and DPP II) is investigated by evaluation of N-substituted Gly-PsiCF=Cpyrrolidines, Gly-PsiCF=Cpiperidines, and Gly-PsiCF=C(2-cyano)pyrrolidines. Of this later class, the (Z)- and (E)-fluoro-olefin analogues were prepared and chemical stability in comparison with the parent amide was checked. Most of these compounds exhibited a strong binding preference toward DPP II with IC(50) values in the low micromolar range, while only low DPP IV inhibitory potential is seen.