1-((3S, 4S)-4-Amino-1-(4-substituted-1, 3, 5-triazin-2-yl) pyrrolidin-3-yl)-5, 5-difluoropiperidin-2-one inhibitors of DPP-4 for the treatment of type 2 diabetes

…, S Liu, RK McPherson, C Neagu, JC Parker…

Index: Andrews, Kim M.; Beebe, David A.; Benbow, John W.; Boyer, David A.; Doran, Shawn D.; Hui, Yu; Liu, Shenping; McPherson, R. Kirk; Neagu, Constantin; Parker, Janice C.; Piotrowski, David W.; Schneider, Steven R.; Treadway, Judith L.; Vanvolkenberg, Maria A.; Zembrowski, William J. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 6 p. 1810 - 1814

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Citation Number: 13

Abstract

A 3-amino-4-substituted pyrrolidine series of dipeptidyl peptidase IV (DPP-4) inhibitors was rapidly developed into a candidate series by identification of a polar valerolactam replacement for the lipophilic 2, 4, 5-trifluorophenyl pharmacophore. The addition of a gem- difluoro substituent to the lactam improved overall DPP-4 inhibition and an efficient asymmetric route to 3, 4-diaminopyrrolidines was developed. Advanced profiling of a ...