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Based on a receptor-interaction model, structural modifications of the benzene and pyridine rings led to the identification of compound 26 (Figure 5), which includes a 2,4-dichlorophenyl group at two positions, as a potent (IC 50 = 0.13 M), selective (DPP-8/DPP-4 = 215, DPP-9/DPP-4 = 192), and in vivo efficacious DPP-4 inhibitor