Premium
Design and Synthesis of A‐Ring Simplified Pyripyropene A Analogues as Potent and Selective Synthetic SOAT2 Inhibitors
Author(s) -
Ohtawa Masaki,
Arima Shiho,
Ichida Naoki,
Terayama Tomiaki,
Ohno Hironao,
Yamazaki Takaya,
Ohshiro Taichi,
Sato Noriko,
Omura Satoshi,
Tomoda Hiroshi,
Nagamitsu Tohru
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700645
Subject(s) - stereochemistry , ring (chemistry) , aspergillus fumigatus , chemistry , pharmacophore , structure–activity relationship , chemical synthesis , sterol o acyltransferase , combinatorial chemistry , total synthesis , biochemistry , biology , in vitro , cholesterol , organic chemistry , lipoprotein , microbiology and biotechnology
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 anti‐atherosclerotic agents, new A‐ring simplified pyripyropene A analogues have been designed and synthesized based on total synthesis, and the results of structure–activity relationship studies of pyripyropene A. Among the analogues, two A‐ring simplified pyripyropene A analogues exhibited equally efficient SOAT2 inhibitory activity to that of natural pyripyropene A. These new analogues 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.