3 years ago

Design and Synthesis of A-Ring Simplified Pyripyropene A Analogs as Potent and Selective Synthetic SOAT2 Inhibitors

Taichi Ohshiro, Satoshi Omura, Hiroshi Tomoda, Hironao Ohno, Takaya Yamazaki, Naoki Ichida, Shiho Arima, Noriko Sato, Masaki Ohtawa, Tohru Nagamitsu, Tomiaki Terayama
Currently, pyripyropene A, which is isolated from the culture broth of Aspergillus fumigatus FO-1289, is the only compound known to strongly and selectively inhibit the isozyme sterol O-acyltransferase 2 (SOAT2). To aid in the development of new cholesterol-lowering or antiatherosclerotic agents, new A-ring simplified pyripyropene A analogs were designed and synthesized based on the total synthesis and the results of the structure-activity relationship studies of pyripyropene A achieved by our group. Among the analogs, two A-ring simplified pyripyropene A analogs exhibited equally efficient SOAT2 inhibitory activity compared with that of natural pyripyropene A. These new analogs are the most potent and selective SOAT2 inhibitors to be used as synthetic compounds and attractive seed compounds for the development of drug for dyslipidemia, including atherosclerotic disease and steatosis.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/cmdc.201700645

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