Bioorganic & Medicinal Chemistry Letters 2012-02-01

Substituents at the naphthalene C3 position of (-)-Cercosporamide derivatives significantly affect the maximal efficacy as PPARγ partial agonists.

Akihiro Furukawa, Tsuyoshi Arita, Takehiro Fukuzaki, Susumu Satoh, Makoto Mori, Takeshi Honda, Yumi Matsui, Kenji Wakabayashi, Shinko Hayashi, Kazushi Araki, Jun Ohsumi

Index: Bioorg. Med. Chem. Lett. 22(3) , 1348-51, (2012)

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Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a potential drug target for treating type 2 diabetes. The selective PPARγ modulators (SPPARMs), which partially activate the PPARγ transcriptional activity, are considered to improve the plasma glucose level with attenuated PPARγ related adverse effects. However, the relationships between desired pharmacological profiles and ligand specific PPARγ transcriptional profiles have been unclear. And there is also little knowledge of how to control ligand specific PPARγ transcriptional profiles. Herein, we present synthesis of novel derivatives containing substituent at naphthalene C3 position of compound 1. The novel derivatives showed various maximal efficacies as PPARγ partial agonist.Copyright © 2011 Elsevier Ltd. All rights reserved.