Selected pyrrolidines, 2-cyanopyrrolidines and heteroaromatic isoindoline analogues were evaluated as P1-residues in dipeptide-derived inhibitors of DPP8/9. Potency testing indicates that DPP8 or DPP9 specificity cannot be obtained with the selected set of P1- and P2-fragments. Nonetheless, the nanomolar DPP8/9 potencies and remarkable selectivities with respect to DPP IV and DPPII, makes inhibitors 4c and 4h suitable "leads" for future inhibitor optimization effort.
