Design and synthesis of novel androgen receptor antagonists with sterically bulky icosahedral carboranes
Design and synthesis of novel androgen receptor antagonists with sterically bulky icosahedral carboranes
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DOI：
10.1016/j.bmc.2005.06.061
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发表时间：
2005-12-01
影响因子：
3.5
通讯作者：
Endo, Y
中科院分区：
文献类型：
--
作者：
Goto, T;Ohta, K;Endo, Y
碳硼烷（dicarba-c/oso-dodecoboranes）是一类含碳多面体硼原子簇化合物，具有优异的化学稳定性、热稳定性和疏水性。这些特征可能允许碳硼烷作为一种新的疏水核心结构在与受体疏水相互作用的生物活性分子中的应用。在这里，我们报告的设计和合成新的雄激素拮抗剂轴承碳硼烷部分。这些化合物，特别是8a、8 e和9d，在使用人AR表达质粒转染的NIH 3 T3细胞的报道基因测定中显示出与公知的抗雄激素荧光素类似的抗雄激素活性。碳硼烷笼似乎是表达AR拮抗活性的特权疏水药效团。(c)2005爱思唯尔有限公司保留所有权利。
Carboranes (dicarba-c/oso-dodecaboranes) are a class of carbon-containing polyhedral boron-cluster compounds having remarkable chemical and thermal stability, and hydrophobic character. These features may allow application of carboranes as a new hydrophobic core structure in biologically active molecules that interact hydrophobically with receptors. Here, we report the design and synthesis of novel androgen antagonists bearing a carborane moiety. These compounds, particularly 8a, 8e, and 9d, exhibited anti-androgenic activity similar to that of the well-known anti-androgen flutamide in reporter gene assay using NIH3T3 cells transfected with a human AR expression plasmid. The carborane cage seems to be a privileged hydrophobic pharmacophore for the expression of AR-antagonistic activity. (c) 2005 Elsevier Ltd. All rights reserved.