Bioorganic & Medicinal Chemistry Letters 2004-03-08

Fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors.

Charles G Caldwell, Ping Chen, Jiafang He, Emma R Parmee, Barbara Leiting, Frank Marsilio, Reshma A Patel, Joseph K Wu, George J Eiermann, Aleksandr Petrov, Huaibing He, Kathryn A Lyons, Nancy A Thornberry, Ann E Weber

Index: Bioorg. Med. Chem. Lett. 14 , 1265, (2004)

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Abstract

Amides derived from fluorinated pyrrolidines and 4-substituted cyclohexylglycine analogues have been prepared and evaluated as inhibitors of dipeptidyl dipeptidase IV (DP-IV). Analogues which incorporated (S)-3-fluoropyrrolidine showed good selectivity for DP-IV over quiescent cell proline dipeptidase (QPP). Compound 48 had good pharmacokinetic properties and was orally active in an oral glucose tolerance test in lean mice.