Translations:Discovery and development of dipeptidyl peptidase-4 inhibitors/3/en

In 1994, researchers from Zeria Pharmaceuticals unveiled cyanopyrrolidines with a nitrile function group that was assumed to form an imidate with the catalytic serine. Concurrently other DPP-4 inhibitors without a nitrile group were published but they contained other serine-interacting motifs, e.g. boronic acids, phosphonates or diacyl hydroxylamines. These compounds were not as potent because of the similarity of DPP-4 and prolyl oligopeptidase (PEP) and also suffered from chemical instability. Ferring Pharmaceuticals filed for patent on two cyanopyrrolidine DPP-4 inhibitors, which they published in 1995. These compounds had excellent potency and improved chemical stability.