Discovery of novel dihydrobenzofuran cyclopropane carboxylic acid based calcium sensing receptor antagonists for the treatment of osteoporosis
作者:Gui-Bai Liang、Changyou Zhou、Xianghong Huo、Hank Wang、Xuelin Yang、Shaoqiang Huang、Haisheng Wang、Hilary Wilkinson、Lusong Luo、Wei Tang、David Sutton、Hong Li、Dennis Zaller、Peter T. Meinke
DOI:10.1016/j.bmcl.2016.06.073
日期:2016.8
In a search for novel small molecule calcium-sensing receptor (CaSR) antagonists as oral bone anabolic agents, we discovered dihydrobenzofuran cyclopropane carboxylic acid derivatives, such as 12f (IC50=27.6nM), are highly potent calcium-sensing receptor antagonists. Studies in rats established that compound 12f stimulates parathyroid hormone (PTH) release in a fast-acting, pulsatile manner.
在寻找新型的小分子钙敏感受体(CaSR)拮抗剂作为口服骨合成代谢药物时,我们发现二氢苯并呋喃环丙烷羧酸衍生物,例如12f(IC50 = 27.6nM),是高效的钙敏感受体拮抗剂。在大鼠中的研究证实,化合物12f以快速作用的搏动方式刺激甲状旁腺激素(PTH)的释放。