2-Substitiuted Thio- and Amino-5,8-dimethoxy-1,4-naphthoquinones as a Novel Class of Acyl-CoA: Cholestrol Acyltransferase Inhibitors

,* ‡ A series of 2-alkyl or 2-arylthio-5,8-dimethoxy-1,4-naphthoquinones (2-Thio-DMNQ, 5a-s) and 2-alkylamino-5,8dimethoxy-1,4-naphthoquinones (2-Amino-DMNQ, 6a-k) was synthesized and evaluated for their ACAT inhibitory activities. Among them, the 2-dodecylthio-DMNQ 5l and 2-isobutylamidoundodecylthio-DMNQ 5r showed the most potent ACAT inhibitory activities with IC50 value of 22.8 and 24.4 µM, respectively. In a structure-activity relationship study, 2-thio-DMNQs with side chains of carbon number 11 ~ 15 exhibited significant ACAT inhibitory activities.