Novel Heterocyclic Dpp-4 Inhibitors for the Treatment of Type 2 Diabetes.

Abstract Novel deazaxanthine-based DPP-4 inhibitors have been identified that are potent (IC 50 3a resulted in the identification of compound ( S )- 4i , which displayed an improved in vitro and ADME profile. Further enhancements to the PK profile were possible by changing from the deazahypoxanthine to the deazaxanthine template, culminating in compound 12g , which displayed good ex vivo DPP-4 inhibition and a superior PK profile in rat, suggestive of once daily dosing in man.