Aryl- and heteroaryl-substituted aminobenzo[ a]quinolizines as dipeptidyl peptidase IV inhibitors

Abstract

Synthesis and SAR are described for a structurally distinct class of DPP–IV inhibitors based on aminobenzo[ a]quinolizines bearing (hetero-)aromatic substituents in the S1 specificity pocket. The m-(fluoromethyl)-phenyl derivative ( S,S,S)- 2g possesses the best fit in the S1 pocket. However, ( S,S,S)- 2i, bearing a more hydrophilic 5-methyl-pyridin-2-yl residue as substituent for the S1 pocket, displays excellent in vivo activity and superior drug-like properties.