Abstract
Following the discovery of N-acyl-1,4-diazepan-2-one as a novel pharmacophore for potent and selective DPP-4 inhibitors, optimization of this new lead with different substitution on the seven-membered ring resulted in several highly potent and selective, orally bioavailable, and efficacious DPP-4 inhibitors, such as 3 R-methyl-1-cyclopropyl-1,4-diazepan-2-one derivative 9i (DPP-4 IC 50 = 8.0 nM) and 3 R,6 R-dimethyl-1,4-diazepan-2-one derivative 14a (DPP-4 IC 50 = 9.7 nM).
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