Inhibitors of dipeptidyl peptidase 8 and dipeptidyl peptidase 9. Part 1: identification of dipeptide derived leads.

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Van der Veken P, De Meester I, Dubois V, Soroka A, Van Goethem S, Maes MB, Brandt I, Lambeir AM, Chen X, Haemers A, Scharpe S, Augustyns K

Inhibitors of dipeptidyl peptidase 8 and dipeptidyl peptidase 9. Part 1: identification of dipeptide derived leads.

Bioorg Med Chem Lett. 2008 Jul 15;18(14):4154-8. doi: 10.1016/j.bmcl.2008.05.080. Epub 2008 May 24.

PubMed ID
18556199 [ View in PubMed
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Abstract

Dipeptide derivatives bearing various P2 residues and pyrrolidine derivatives as P1 mimics were evaluated in order to identify lead structures for the development of DPP8 and DPP9 inhibitors. Structure-activity-relationship data obtained in this way led to the preparation of a series of alpha-aminoacyl ((2S, 4S)-4-azido-2-cyanopyrrolidines). These compounds were shown to be nanomolar DPP8/9 inhibitors with modest overall selectivity toward DPP IV and DPP II.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
2-Amino-3-Methyl-1-Pyrrolidin-1-Yl-Butan-1-OneDipeptidyl peptidase 4IC 50 (nM)5400N/AN/ADetails
SitagliptinDipeptidyl peptidase 4IC 50 (nM)40N/AN/ADetails
VildagliptinDipeptidyl peptidase 4Ki (nM)17000N/AN/ADetails
VildagliptinDipeptidyl peptidase 4IC 50 (nM)120N/AN/ADetails