Seco-prolinenitrile inhibitors of dipeptidyl peptidase IV define minimal pharmacophore requirements at P1
David R Magnin1, Prakash C Taunk, James G Robertson
1Department of Discovery Chemistry, Bristol-Myers Squibb, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
Bioorganic & Medicinal Chemistry Letters
|December 27, 2005
Abstract:
A series of seco-prolinenitrile-containing dipeptides were synthesized and assayed as inhibitors of the N-terminal sequence-specific serine protease dipeptidyl peptidase IV, a promising new target for treatment of type 2 diabetes. The inhibitors described herein assess the minimum structural requirements at P1 for this enzyme, resulting in the identification of inhibitors with low nM potency.
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