Substituents at the naphthalene C3 position of (-)-Cercosporamide derivatives significantly affect the maximal efficacy as PPARγ partial agonists.
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.
Shinagawa R&D Center, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, Japan. furukawa.akihiro.zy@daiichisankyo.co.jp
Akihiro
A
Furukawa
Tsuyoshi
T
Arita
Takehiro
T
Fukuzaki
Susumu
S
Satoh
Makoto
M
Mori
Takeshi
T
Honda
Yumi
Y
Matsui
Kenji
K
Wakabayashi
Shinko
S
Hayashi
Kazushi
K
Araki
Jun
J
Ohsumi
D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D047495:PPAR gamma / Q000819:agonists*
D001572:Benzofurans; D007004:Hypoglycemic Agents; D009281:Naphthalenes; D047495:PPAR gamma; C085452:cercosporamide