Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors

The synthesis and structure- activity relationships of novel dipeptidyl peptidase IV inhibitors replacing the classical cyanopyrrolidine P1 group with other small nitrogen heterocycles are described. A unique potency enhancement was achieved with beta-branched natural and unnatural amino acids, particularly adamantylglycines, linked to a (2S, 3R)-2,3-methanopyrrolidine based scaffold. (c) 2007 Elsevier Ltd. All rights reserved.