(Journal Article): 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavail-able dipeptidyl peptidase IV inhibitor with antihyperglycemic properties.
 
Villhauer EB, Brinkman JA, Naderi GB, Burkey BF, Dunning BE, Prasad K, Mangold BL, Russell ME, Hughes TE (Novartis Institute for Biomedical Research, One Health Plaza, East Hanover, New Jersey 07936, USA., edwin.villhauer@pharma.novartis.com )
 
IN: J Med Chem 2003; 46(13):2774-2789
Impact Factor(s) of J Med Chem: 5.076 (2004), 4.82 (2003), 4.566 (2002), 4.139 (2001)

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ABSTRACT: Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2-[5-cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano-(S)-pyrrolidine (NVP-DPP728, 8c) to its follow-up, 1-[[(3-hydroxy-1-adamantyl) amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP-LAF237, 12j). The pharmacological profile of 12j in obese Zucker fa/fa rats along with pharmacokinetic profile comparison of 8c and 12j in normal cynomolgus monkeys is discussed. The results suggest that 12j is a potent, stable, selective DPP-IV inhibitor possessing excellent oral bioavailability and potent antihyperglycemic activity with potential for once-a-day administration.

TYPE OF PUBLICATION: Original article

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• Gallwitz B. New Therapeutic Strategies for the Treatment of Type 2 Diabetes Mellitus Based on Incretins. Rev Diabetic Stud 2005. 2: 61-69.
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