Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV.

Article Details

Citation

Zhang Z, Wallace MB, Feng J, Stafford JA, Skene RJ, Shi L, Lee B, Aertgeerts K, Jennings A, Xu R, Kassel DB, Kaldor SW, Navre M, Webb DR, Gwaltney SL

Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV.

J Med Chem. 2011 Jan 27;54(2):510-24. doi: 10.1021/jm101016w. Epub 2010 Dec 27.

PubMed ID
21186796 [ View in PubMed
]
Abstract

The discovery of two classes of heterocyclic dipeptidyl peptidase IV (DPP-4) inhibitors, pyrimidinones and pyrimidinediones, is described. After a single oral dose, these potent, selective, and noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and lowering of blood glucose in animal models of diabetes. Compounds 13a, 27b, and 27j were selected for development.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AlogliptinDipeptidyl peptidase 4IC 50 (nM)7N/AN/ADetails