Novel Pyrazole Derivatives Effectively Inhibit Osteoclastogenesis, a Potential Target for Treating Osteoporosis

Ting Hao Kuo, Tzu Hung Lin, Rong Sen Yang, Sheng Chu Kuo, Wen Mei Fu, Hsin-Yi Hung

研究成果: Article同行評審

12 引文 斯高帕斯(Scopus)

摘要

As human beings live longer, age-related diseases such as osteoporosis will become more prevalent. Intolerant side effects and poor responses to current treatments are observed. Therefore, novel effective therapeutic agents are greatly needed. Here, pyrazole derivatives were designed and synthesized, and their osteoclastogenesis inhibitory effects both in vitro and in vivo were evaluated. The most promising compound 13 with a 2-(dimethylamino)ethyl group inhibited markedly in vitro osteoclastogenesis as well as the bone resorption activity of osteoclasts. Compound 13 affected osteoclasts early proliferation and differentiation more than later fusion and maturation stages. In ovariectomized (OVX) mice, compound 13 can inhibit the loss of trabecular bone volume, trabecular bone number, and trabecular thickness. Moreover, compound 13 can antagonize OVX-induced reduction of serum bone resorption marker and then compensatory increase of the bone formation marker. To sum up, compound 13 has high potential to be developed into a novel therapeutic agent for treating osteoporosis in the future.

原文English
頁(從 - 到)4954-4963
頁數10
期刊Journal of Medicinal Chemistry
58
發行號12
DOIs
出版狀態Published - 2015 六月 25

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 藥物發現

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