Design, synthesis and SARs of novel salicylanilides as potent inhibitors of RANKL-induced osteoclastogenesis and bone resorption

Chun Liang Chen, Chia Chung Lee, Fei Lan Liu, Tsung Chih Chen, Ahmed Atef Ahmed Ali, Deh Ming Chang, Hsu Shan Huang

研究成果: 雜誌貢獻文章同行評審

9 引文 斯高帕斯(Scopus)

摘要

Inhibiting osteoclastogenesis is a promising therapeutic target for treating osteoclast-related diseases. Herein, we synthesized a series of modified salicylanilides and their corresponding 3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione and 10-phenyldibenzo[b,f][1,4]oxazepin-11(10H)-one derivatives, and investigated the effects of such compounds on RANKL-induced osteoclast formation. Among them, a salicylanilide derivative (A04) and its 3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivative (B04) markedly suppressed RANKL-induced osteoclast differentiation and showed no significant cytotoxic effects at doses higher than that required to inhibit osteoclast formation. Both compounds reduced osteoclast formation and bone resorptive activity of osteoclasts in a dose-dependent manner. Further, the anti-osteoclastogenic effects of A04 and B04 may operate through reducing the RANKL-induced nuclear translocation of NFATc1. Accordingly, we present the potent anti-osteoclastogenic compounds A04 and B04 as promising candidates for further optimization as anti-resorptive agents.
原文英語
頁(從 - 到)70-84
頁數15
期刊European Journal of Medicinal Chemistry
117
DOIs
出版狀態已發佈 - 七月 19 2016

ASJC Scopus subject areas

  • 藥物發現
  • 有機化學
  • 藥理

指紋

深入研究「Design, synthesis and SARs of novel salicylanilides as potent inhibitors of RANKL-induced osteoclastogenesis and bone resorption」主題。共同形成了獨特的指紋。

引用此