2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV

• Published in: Bioorganic & medicinal chemistry letters 2005-12, Vol.15 (23), p.5257-5261
• Main Authors: Haffner, Curt D., McDougald, Darryl L., Reister, Steven M., Thompson, Brian D., Conlee, Christopher, Fang, Jing, Bass, Jonathan, Lenhard, James M., Croom, Dallas, Secosky-Chang, Melissa B., Tomaszek, Thaddeus, McConn, Donavon, Wells-Knecht, Kevin, Johnson, Paul R.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Dipeptidyl Peptidase 4 - metabolism; Dipeptidyl peptidase IV; Dogs; DPP-IV; General and cellular metabolism. Vitamins; Glucagon-like peptide 1; Glucose-dependent inhibitory polypeptide; Medical sciences; Pharmacology. Drug treatments; Protease Inhibitors - chemical synthesis; Protease Inhibitors - chemistry; Protease Inhibitors - pharmacology; Pyrrolidines - chemical synthesis; Pyrrolidines - chemistry; Pyrrolidines - pharmacology; Rats; Valine - analogs & derivatives; Valine - chemical synthesis; Valine - chemistry; Valine - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.08.050

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. 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.