title: Synthesis of a novel class of substituted benzothiophene or benzofuran derivatives as BMP-2 up-regulators and evaluation of the BMP-2-up-regulating effects in vitro and the effects on glucocorticoid-induced osteoporosis in rats.
abstract: The BMP pathway is a promising new target for the design of therapeutic agents for the treatment of low bone mass. To enrich our understanding of SAR and based on our previously concluded structure-effect relationship, 23 derivatives were prepared in this work. The synthesis, up-regulating activities on BMP-2 expression, and bone loss prevention efficacies of these compounds in rats with glucocorticoid-induced osteoporosis are presented. The bone histology of the tested rats assessed through light microscopy showed that compounds 1, 21, 35, and 38 significantly increased the trabecula compared with the model group, and the trabecula of the groups treated with 8a was similar to that obtained with raloxifene and alfacalcidol. The compounds exhibited potential for development as anabolic agents.
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors: Si-tu
authors: ST
authors: Xue
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors: Hui-fang
authors: HF
authors: Guo
authors: Institute of Basic Theories, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors: Mei-jie
authors: MJ
authors: Liu
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors: Jie
authors: J
authors: Jin
authors: Institute of Basic Theories, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors: Da-hong
authors: DH
authors: Ju
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: zongyingliu@263.net.
authors: Zong-ying
authors: ZY
authors: Liu
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: l-z-r@263.net.
authors: Zhuo-rong
authors: ZR
authors: Li
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D005938:Glucocorticoids; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C525718:BMP2 protein, human; D001572:Benzofurans; D055396:Bone Morphogenetic Protein 2; D005938:Glucocorticoids; D013876:Thiophenes; C088015:benzothiophene; C105430:benzofuran
keywords: Benzofuran; Benzothiophene; Bone morphogenetic protein-2; Osteoporosis