From lead to preclinical candidate: optimization of beta-homophenylalanine based inhibitors of dipeptidyl peptidase IV.

Sonja Nordhoff, Meritxell López-Canet, Barbara Hoffmann-Enger, Stephan Bulat, Silvia Cerezo-Gálvez, Oliver Hill, Claudia Rosenbaum, Christian Rummey, Meinolf Thiemann, Victor G Matassa, Paul J Edwards, Achim Feurer

Index: Bioorg. Med. Chem. Lett. 19(16) , 4818-23, (2009)

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Abstract

A series of highly potent and selective inhibitors of DPP-4 was optimized for ADMET properties. The effort resulted in the discovery of inhibitor 1g, that exhibits excellent efficacy in an oral glucose tolerance test and an attractive pharmacokinetic profile.