Aminomethylpyrimidines as novel DPP-IV inhibitors:: A 105-fold activity increase by optimization of aromatic substituents

The influence of aromatic substitution on a newly discovered class of inhibitors of dipeptidyl peptidase IV was investigated. A 10(5)-fold increase in potency was achieved by the optimization of aromatic substituents in a parallel chemistry program. The observed SAR could be explained by an X-ray structure of the protein-ligand complex. (C) 2004 Elsevier Ltd. All rights reserved.