Synthesis and structure–activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors: Part 1

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Abstract

In an effort to develop potent and selective inhibitors toward ACAT2, structure–activity relationship studies were carried out using derivatives based on pyripyropene A (PPPA, 1). We have successfully developed novel PPPA derivatives with a 7-O-substituted benzoyl substituent that significantly exhibit more potent ACAT2 inhibitory activity and higher ACAT2 isozyme selectivity than 1.

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Acknowledgments

This work was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO) (H.T.), and by a grant-in-aid for Scientific Research (B) 18390008 (H.T.). The authors thank the following groups: Meiji Seika Pharma Co., Ltd. for their extensive cooperation; ChemGenesis and PharmaDesign, Inc. for their valuable advice; and Chemical Analysis Center (Kitasato Univ., Ms. Sato and Dr. Nagai) for kindly measuring NMR and MS

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