Novel diether compounds inhibiting differentiation of osteoclasts

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• 作者：Kyung Eun Doh ; Ju-Hee Kang ; Zheng Ting ; Mijung Yim…
• 关键词：Osteoporosis ; Osteoclast ; Differentiation ; RANKL
• 刊名：Archives of Pharmacal Research
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：39
• 期：2
• 页码：178-190
• 全文大小：1,010 KB
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• 作者单位：Kyung Eun Doh (1)
  Ju-Hee Kang (2)
  Zheng Ting (2)
  Mijung Yim (2)
  Hea-Young Park Choo (1)
  
  1. College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea
  2. College of Pharmacy, Sookmyung Women’s University, Seoul, 140-742, Republic of Korea
  
• 刊物主题：Pharmacy; Pharmacology/Toxicology;
• 出版者：Springer Netherlands
• ISSN：1976-3786

文摘

Osteoporosis is a disorder in which bone mass decreases and is responsible for many degenerative bone diseases. The excessive formation and activity of osteoclasts results in pathological disorders of the bone. Receptor Activator of Nuclear Factor κB Ligand (RANKL) is regarded as a key regulator of osteoclast activity and as a new therapeutic target for treating osteoporosis. Herein, we have synthesized several new small molecules and tested their inhibition activity on RANKL-induced osteoclast formation. The active compounds 2c and 4d showed inhibitory activity against RANKL-induced osteoclast differentiation (IC₅₀ = 1.56 and 2.20 μM, respectively). The most active compound 2c prevented LPS-induced osteoclastogenesis in vivo. These data imply that the compound may be the potential candidate for a new therapeutic drug for treatment of bone resorption-associated diseases.