Synthesis and Diacylglycerol Acyltransferase-1 Inhibition of Azabicyclo[3.1.0]hexane Derivatives

摘要

We identified azabicyclo[3.1.0]hexane derivatives that are active diacylglycerol acyltransferase-1 (DGAT)-1 inhibitor. Among the azabicyclo[3.1.0]hexane series, compound 6b showed good in vitro activity toward human DGAT-1, selectivity toward DGAT-2, and liver microsomal stability. Compound 6b exhibited no CYP inhibition, hERG binding, or cell cytotoxicity. Additionally, compound 6b reduced the level of plasma triglyceride after oral administration in mice.