Norman Bryan H, Richardson Timothy I, Dodge Jeffrey A, Pfeifer Lance A, Durst Gregory L, Wang Yong, Durbin Jim D, Krishnan Venkatesh, Dinn Sean R, Liu Shengquan, Reilly John E, Ryter Kendal T
Discovery Chemistry Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Bioorg Med Chem Lett. 2007 Sep 15;17(18):5082-5. doi: 10.1016/j.bmcl.2007.07.009. Epub 2007 Jul 13.
Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER receptor subtypes alpha and beta in opposite orientations. We have used structure based drug design to show that this unique phenomena can be exploited via substitution at the 8-position of the benzopyran A-ring to disrupt binding to ERalpha, thus improving ERbeta subtype selectivity. X-ray cocrystal structures with ERalpha and ERbeta are supportive of this approach to improve selectivity in this structural class.
苯并吡喃是选择性雌激素受体（ER）β激动剂（SERBAs），它们以相反的方向与ER受体亚型α和β结合。我们利用基于结构的药物设计表明，这种独特的现象可以通过在苯并吡喃A环的8位进行取代来利用，以破坏与ERα的结合，从而提高ERβ亚型的选择性。与ERα和ERβ的X射线共晶体结构支持这种在该结构类别中提高选择性的方法。
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