Synthesis and Biological Evaluation of Cyclopentaquinoline Derivatives as Nonsteroidal Glucocorticoid Receptor Antagonists

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• 作者：Masahiro Eda ; Tomoko Kuroda ; Satoshi Kaneko ; Yoshiyuki Aoki ; Masami Yamashita ; Chieko Okumura ; Yoshitaka Ikeda ; Tomoko Ohbora ; Masaki Sakaue ; Natsumi Koyama ; Keiichi Aritomo
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：June 25, 2015
• 年：2015
• 卷：58
• 期：12
• 页码：4918-4926
• 全文大小：367K
• ISSN：1520-4804

文摘

The steroidal glucocorticoid antagonist mifepristone has been reported to improve the symptoms of depression. We report the discovery of 6-(3,5-dimethylisoxazol-4-yl)-2,2,4,4-tetramethyl-2,3,4,7,8,9-hexahydro-1H-cyclopenta[h]quinolin-3-one 3d (QCA-1093) as a novel nonsteroidal glucocorticoid receptor antagonist. The compound displayed potent in vitro activity, high selectivity over other steroid hormone receptors, and significant antidepressant-like activity in vivo.