1. 2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV
- Author
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Jonathan Y. Bass, Melissa B. Secosky-Chang, Dallas K. Croom, Paul R. Johnson, Steven Michael Reister, Curt D. Haffner, Jing Fang, Thaddeus A. Tomaszek, Christopher R. Conlee, Donavon J McConn, Darryl Lynn Mcdougald, Kevin J. Wells-Knecht, James M. Lenhard, and Brian Thompson
- Subjects
animal structures ,Pyrrolidines ,Nitrile ,Stereochemistry ,Dipeptidyl Peptidase 4 ,Clinical Biochemistry ,Pharmaceutical Science ,Administration, Oral ,Biochemistry ,Chemical synthesis ,Sulfone ,chemistry.chemical_compound ,Dogs ,Oral administration ,Drug Discovery ,Animals ,heterocyclic compounds ,Protease Inhibitors ,Molecular Biology ,Dipeptidyl peptidase-4 ,chemistry.chemical_classification ,biology ,Organic Chemistry ,Biological activity ,Valine ,Rats ,Enzyme ,chemistry ,Enzyme inhibitor ,biology.protein ,Molecular Medicine - Abstract
We report the synthesis and biological activity of a series of 2-cyano-4-fluoro-1-thiovalylpyrrolidine inhibitors of DPP-IV. Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog.
- Published
- 2005