3-芳基苯并恶嗪作为选择性雌激素受体β激动剂的合成及构效关系

Synthesis and structure-activity relationship of 3-arylbenzoxazines as selective estrogen receptor beta agonists.

作者信息

Yang Wu, Wang Yufeng, Ma Zhengping, Golla Rajasree, Stouch Terry, Seethala Ramakrishna, Johnson Susan, Zhou Rong, Güngör Timur, Feyen Jean H M, Dickson John K

机构信息

Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.

出版信息

Bioorg Med Chem Lett. 2004 May 3;14(9):2327-30. doi: 10.1016/j.bmcl.2004.01.099.

DOI:10.1016/j.bmcl.2004.01.099

PMID:15081034

Abstract

A series of 3-aryl-7-hydroxybenzoxazine analogues have been prepared and evaluated as ligands for the two estrogen receptor subtypes (ERalpha and ERbeta). From the radioligand binding assay, compounds with more than a 10-fold binding selectivity toward the ERbeta subtype have been identified. These compounds have also been shown to be potent full agonists in the functional assay by activation of ERE promoted transcription, with the best compound being 20-fold more potent than genistein.

摘要

已制备了一系列3-芳基-7-羟基苯并恶嗪类似物，并将其作为两种雌激素受体亚型（ERα和ERβ）的配体进行评估。通过放射性配体结合试验，已鉴定出对ERβ亚型具有超过10倍结合选择性的化合物。在功能试验中，这些化合物还通过激活雌激素反应元件（ERE）促进的转录而被证明是有效的完全激动剂，其中最佳化合物的效力比染料木黄酮高20倍。