Discovery of beta-aminoacyl containing thiazolidine derivatives as potent and selective dipeptidyl peptidase IV inhibitors.

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Park WS, Kang SK, Jun MA, Shin MS, Kim KY, Rhee SD, Bae MA, Kim MS, Kim KR, Kang NS, Yoo SE, Lee JO, Song DH, Silinski P, Schneider SE, Ahn JH, Kim SS

Discovery of beta-aminoacyl containing thiazolidine derivatives as potent and selective dipeptidyl peptidase IV inhibitors.

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1366-70. doi: 10.1016/j.bmcl.2011.01.041. Epub 2011 Jan 14.

PubMed ID
21306895 [ View in PubMed
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Abstract

A series of beta-aminoacyl containing thiazolidine derivatives was synthesized and evaluated for their ability to inhibit DPP-IV. Several thiazolidine derivatives with an acid moiety were found to be potent DPP-IV inhibitors. Among them, compound 2da is the most active in this series with an IC(50) value of 1 nM, and it showed excellent selectivity over DPP-IV related enzymes including DPP-2, DPP-8, and DPP-9. Compound 2da is chemically and metabolically stable, and showed no CYP inhibition, hERG binding or cytotoxicity. Compound 2db, an ester prodrug of 2da, showed good in vivo DPP-IV inhibition after oral administration in rat and dog models.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
SitagliptinDipeptidyl peptidase 4IC 50 (nM)20N/AN/ADetails