Caldwell Charles G, Chen Ping, He Jiafang, Parmee Emma R, Leiting Barbara, Marsilio Frank, Patel Reshma A, Wu Joseph K, Eiermann George J, Petrov Aleksandr, He Huaibing, Lyons Kathryn A, Thornberry Nancy A, Weber Ann E
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA.
Bioorg Med Chem Lett. 2004 Mar 8;14(5):1265-8. doi: 10.1016/j.bmcl.2003.12.040.
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.
已制备了源自氟化吡咯烷和4-取代环己基甘氨酸类似物的酰胺，并将其作为二肽基二肽酶IV（DP-IV）抑制剂进行了评估。含有（S）-3-氟吡咯烷的类似物对DP-IV的选择性优于静止细胞脯氨酸二肽酶（QPP）。化合物48具有良好的药代动力学性质，并且在瘦小鼠的口服葡萄糖耐量试验中具有口服活性。
