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

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8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)70-84
Number of pages15
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - Jul 19 2016



  • 3-Phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione
  • NFATc1
  • Osteoclast
  • Salicylanilide

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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