Design and synthesis of novel 3-substituted-indole derivatives as selective H₃ receptor antagonists and potent free radical scavengers

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• 作者：Li Tang ; Liying Zhao ; Lingjuan Hong ; Fenyan Yang ; Rong Sheng ; Jianzhong Chen ; Ying Shi ; Naimin Zhou ; Yongzhou Hu
• 关键词：H3 receptor antagonists ; Free radical scavengers ; Melatonin ; Benzyl tertiary amine
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 October, 2013
• 年：2013
• 卷：21
• 期：19
• 页码：5936-5944
• 全文大小：1354 K

文摘

A series of novel 3-substituted-indole derivatives with a benzyl tertiary amino moiety were designed, synthesized and evaluated as H₃ receptor antagonists and free radical scavengers for Alzheimer¡¯s disease therapy. Most of these synthesized compounds exhibited moderate to potent antagonistic activities in CREs driven luciferase assay. In particular, compound 2d demonstrated the most favorable H₃ receptor antagonistic activity with the IC₅₀ value of 0.049 ¦ÌM. Besides, it also displayed high binding affinity to H₃ receptor (K_i = 4.26 ¡À 2.55 nM) and high selectivity over other three histamine receptors. Moreover, 2d and other two 3-substituted indole derivatives 1d and 3d exerted potent ABTS radical cation scavenging capacities similar to melatonin. Above results illustrate that 2d is an interesting lead for extensive optimization to explore new drug candidate for AD therapy.