Abstract:The free fatty acid receptor 1 (FFA1) is a promising anti-diabetic target, and many FFA1 agonists including TAK-875 and AMG-837 are reached in clinical studies. However, the excessive lipophilicity of AMG-837 (ClogP = 6.81) might be a potential downside attributed to the clinical failure of AMG-837. In this study, we introduced the oxime ether moiety to replace the middle benzene of AMG-837 to reduce the lipophilicity. After comprehensive structure-activity relationship study, the optimal compound 7 was identi… Show more
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