Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 19, Issue 7, Pages 1908-1912Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.02.061
Keywords
Glutamic acid; DPP-IV; Inhibitor
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Funding
- National Health Research Institutes, Taiwan
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A series of (2S)-cyanopyrrolidines with glutamic acid derivatives at the P2 site have been prepared and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV). The structure-activity relationships (SAR) led to the discovery of potent 3-substituted glutamic acid analogues, providing enhanced chemical stability and excellent selectivity over the closely related enzymes, DPP8, DPP-II and FAP. Compound 13f exhibited the ability to both significantly decrease the glucose excursion and inhibit plasma DPP-IV activity. (C) 2009 Elsevier Ltd. All rights reserved.
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