Synthesis and evaluation of 1-(benzo[b]thiophen-2-yl)ethanone analogues as novel anti-osteoporosis agents acting on BMP-2 promotor.
A novel series of 1-(benzo[b]thiophen-2-yl)ethanone analogues were prepared and evaluated for enhancing BMP-2 expression. Compounds 1-5, 7, 8, 12, 13 and 16, with upregulation rate values of 35.6%, 27.9%, 39.8%, 32.0%, 37.1%, 30.2%, 28.0%, 33.5%, 22.8% and 27.3% in vitro, respectively, at a concentration of 4muM, exhibited potent effect for enhancing BMP-2 expression. We also found that compounds 1 and 12 produced a dose-dependent increase on bone histology and histomorphometry, and effectively reduced bone defects induced by ovariectomy in an ovariectomized rat model (OVX).
Liu
Zong-ying
ZY
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.
He
Xiao-bo
XB
Yang
Zhao-yong
ZY
Shao
Hua-yi
HY
Li
Xue
X
Guo
Hui-fang
HF
Zhang
Yue-qin
YQ
Si
Shu-yi
SY
Li
Zhuo-rong
ZR
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D001842:Bone and Bones / Q000473:pathology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008956:Models, Chemical; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D011401:Promoter Regions, Genetic; D051381:Rats; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology
D055396:Bone Morphogenetic Protein 2; D013876:Thiophenes