Synthesis and potent inhibitory activities of carboxybenzyl-substituted 8-(3-(R)-aminopiperidin-1-yl)-7-(2-chloro/cyanobenzyl)-3-methyl-3,7-dihydro-purine-2,6-diones as dipeptidyl peptidase IV (DPP-IV) inhibitors

Fourteen 3-methyl-3,7-dihydro-purine-2,6-dione derivatives 1-14 bearing carboxybenzyl and 2-chloro/cyanobenzyl groups at the N-1 and N-7 positions, respectively, were synthesized as dipeptidyl peptidase IV (DPP-IV) inhibitors. These compounds were characterized on the basis of NMR (H-1 and C-13) and ESI MS data. In vitro bioassay indicates that most of these compounds showed moderate to good inhibitory activities against DPP-IV. Among them, compound 13 (IC50 = 36 nM) exhibited comparable activity with a positive control, Sitagliptin (IC50 = 16 nM). In addition, the structure-activity relationship of these compounds is also briefly discussed. (C) 2015 Elsevier Ltd. All rights reserved.