Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.
J Med Chem. 2010 Feb 25;53(4):1819-29. doi: 10.1021/jm901685n.
In this work, substituted benzothiophene and benzofuran compounds were found to be a new class of potential anabolic agents by enhancing BMP-2 expression. A series of benzothiophene and benzofuran derivatives have been synthesized, and their activities of up-regulating BMP-2 and bone loss prevention efficacies in SAMP6 mice and OVX rats have been studied. Benzothiophenes 1, 3, 14, 4a, 7a, 8a, and benzofuran analogue 2 showed higher BMP-2 up-regulation rates in vitro. Compound 8a was found to significantly affect the bone formation rate of tested SAMP6 mice. Compound 1 showed an improved bone quality in SAMP6 mice and also showed activity in OVX rats. We have demonstrated that substituted benzothiophene and benzofuran derivatives, especially compounds 1 and 8a, enhance BMP-2 expression in vitro and in vivo and stimulate bone formation and trabecular connectivity restoration in vivo. The compounds represent potential leads in the development of a new class of anabolic agents.
在这项工作中，通过增强 BMP-2 的表达，我们发现取代的苯并噻吩和苯并呋喃类化合物是一类新的潜在的合成代谢药物。我们合成了一系列苯并噻吩和苯并呋喃衍生物，并研究了它们在 SAMP6 小鼠和去卵巢大鼠中上调 BMP-2 表达和预防骨丢失的活性。苯并噻吩 1、3、14、4a、7a、8a 和苯并呋喃类似物 2 在体外表现出更高的 BMP-2 上调率。化合物 8a 被发现能显著影响测试的 SAMP6 小鼠的骨形成率。化合物 1 在 SAMP6 小鼠中改善了骨质量，并且在去卵巢大鼠中也具有活性。我们已经证明，取代的苯并噻吩和苯并呋喃衍生物，特别是化合物 1 和 8a，能在体外和体内增强 BMP-2 的表达，并刺激体内骨形成和小梁连接的恢复。这些化合物代表了开发新型合成代谢药物的潜在先导化合物。
