Design, Synthesis And Sar Studies Of Novel And Potent Dipeptidyl Peptidase 4 Inhibitors

Main observation and conclusionDipeptidyl peptidase 4 (DPP-4) is a clinically validated target for the treatment of type 2 diabetes mellitus (T2DM). To discover novel and potent DPP-4 inhibitors, three series of compounds were designed and synthesized in this study based on our previously identified novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine. Among the designed compounds, 41d-1 was the most potent one with an IC50 value of 16.00 nM. Besides, 41d-1 (5 mg/kg) displayed a moderate glucose tolerance capability in ICR mice. Structure-activity-relationship (SAR) studies were discussed in detail, which is constructive for our further optimization.