期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 18, 期 4, 页码 1312-1317出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2008.01.027
关键词
glucocorticoid receptor (GR) antagonist; pyrazolo-fused; azadecalins
Addition of the 4-fluorophenylpyrazole group to the previously described 2-azadecalin glucocorticoid receptor (GR) antagonist 1 resulted in significantly enhanced functional activity. SAR of the bridgehead substituent indicated that whereas groups as small as methyl afforded high GR binding, GR functional activity was enhanced by larger groups such as benzyl, substituted ethers, and aminoalkyl derivatives. GR antagonists with binding and functional activity comparable to mifepristone were discovered ( e. g., 52: GR binding K-i 0.7 nM; GR reporter gene functional K-i 0.6 nM) and found to be highly selective over other steroid receptors. Analogues 43 and 45 had > 50% oral bioavailability in the dog. (c) 2008 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据