Discovery of Aryloxy Tetramethylcyclobutanes as Novel Androgen Receptor Antagonists
Discovery of Aryloxy Tetramethylcyclobutanes as Novel Androgen Receptor Antagonists
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DOI：
10.1021/jm201059s
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发表时间：
2011-11-10
影响因子：
7.3
通讯作者：
Fanjul, Andrea N.
中科院分区：
文献类型：
--
作者：
Guo, Chuangxing;Linton, Angelica;Fanjul, Andrea N.
通过基于细胞的高通量筛选，将四氧化四甲基环丁烷鉴定为雄激素受体（AR）拮抗剂的新模板。最初的“命中”的后续作品将5作为可行的潜在客户建立。进一步的优化以实现全AR拮抗作用导致发现了26和30，这两者在cast割耐药的前列腺癌（CRPC）动物模型中对口服给药的体内肿瘤生长抑制作用极好。
An aryloxy tetramethylcyclobutane was identified as a novel template for androgen receptor (AR) antagonists via cell-based high-throughput screening. Follow-up to the initial "hit" established 5 as a viable lead. Further optimization to achieve full AR antagonism led to the discovery of 26 and 30, both of which demonstrated excellent in vivo tumor growth inhibition upon oral administration in a castration-resistant prostate cancer (CRPC) animal model.