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. ? 2009 Elsevier Ltd. All rights reserved.
Date:
2009-04-01
Relation:
Bioorganic and Medicinal Chemistry Letters. 2009 Apr 1;19(7):1908-1912.
