Synthesis and anti-diabetic activity of (RS)-2-ethoxy-3-{4-2-(4-trifluoromethanesulfonyloxy-phenyl)-ethoxy-phenyl}-propionic acid

摘要

Aim: To synthesize and study the anti-diabetic activity of (RS)-2-ethoxy-3-{4-[2-(4-trifluoromethanesulfonyloxy-phenyl)-ethoxy]-phenyl}-propionic acid (compound I). Methods: Compound I was prepared in 6 steps, using 4-(2-hy-droxy-ethyl)-phenol as the starting material. The in vitro selectivity and potency of target compound I, rosiglitazone and WY-14643 on human PPARα and PPARγ were determined in reporter gene assays. In vivo, rosiglitazone and compound I were administered orally to KKAy mice for 14 d. Insulin tolerance tests and oral glucose tolerance tests were performed on the 10th and 14th day of treatment, respectively. At the end of the treatment, sera were collected for biochemical analysis. Results: In vitro, compound I significantly activated both PPARαand PPARγ. In vivo, compound I corrected the impaired insulin and glucose tolerance of KKAy mice, and produced a significant reduction in plasma triglyceride levels after 14 d of treatment. The effect produced was significant compared with the control group. Conclusion: Both in vitro and in vivo anti-diabetic activity studies for compound I were conducted and the data suggest that this compound is a potentially effective anti-diabetic agent.