Potent androgen antagonists based on carborane as a hydrophobic core structure
Potent androgen antagonists based on carborane as a hydrophobic core structure
复制标题
DOI：
10.1021/jm050115j
复制
发表时间：
2005-07-14
影响因子：
7.3
通讯作者：
Endo, Y
中科院分区：
文献类型：
--
作者：
Fujii, S;Goto, T;Endo, Y
碳硼烷（dicarba-closo-dodecoboranes）是一类具有良好化学稳定性、热稳定性和疏水性的多面体硼原子簇化合物。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。我们在这里报告的设计和合成新的雄激素拮抗剂轴承碳硼烷。最有效的化合物，芳基碳硼烷衍生物6 e和6 i，在使用人AR表达质粒转染的NIH 3 T3细胞的报告基因测定中，以及在使用雄激素依赖性SC-3细胞的细胞生长抑制测定中，显示出比公知的抗雄激素羟基芴醇更大的抗雄激素活性。本文所述的有效的含碳硼烷的雄激素拮抗剂具有新的骨架结构和独特的特性，其进一步开发可能产生新的治疗剂，特别是选择性雄激素受体调节剂。
Carboranes (dicarba-closo-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. We report here the design and synthesis of novel androgen antagonists bearing carborane. The most potent compounds, the arylcarborane derivatives 6e and 6i, exhibited antiandrogenic activity greater than that of the well-known antiandrogen hydroxyflutamide in reporter gene assay using NIH3T3 cells transfected with a human AR expression plasmid, as well as in cell growth inhibition assay using androgen-dependent SC-3 cells. Further development of the potent carborane-containing androgen antagonists described here, having a new skeletal structure and unique characteristics, may yield novel therapeutic agents, especially selective androgen receptor modulators.