Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 18, Issue 7, Pages 2409-2413Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2008.02.050
Keywords
fluoroolefin; DPP-4; dipeptidyl peptidase IV; oxadiazole; amide bond mimic; amide bond mimetic; amide bond bioisostere; QPP; DPP-II
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The synthesis, selectivity, rat pharmacokinetic profile, and drug metabolism profiles of a series of potent fluoroolefin-derived DPP-4 inhibitors (4) are reported. A radiolabeled fluoroolefin 33 was shown to possess a high propensity to form reactive metabolites, thus revealing a potential liability for this class of DPP-4 inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.
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