Novel 12N-substituted matrinanes as potential anti-coxsackievirus agents

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• 作者：Ying&ndash ; Hong Li^a ; ¹ ; Sheng Tang^a ; ¹ ; Yu&ndash ; Huan Li^a ; Xin&ndash ; Yue Cheng^a ; Xin Zhang^a ; Yan&ndash ; Xiang Wang^a ; Feng Su^b ; ^{sufengvip@126.com} ; Dan&ndash ; Qing Song^a ; ^{songdanqingsdq@hotmail.com}
• 关键词：Matrinane ; Structure&ndash ; activity relationship ; Coxsakievirus ; Broad-spectrum ; Druglike
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：27
• 期：4
• 页码：829-833
• 全文大小：1181 K
• 卷排序：27

文摘

A series of novel 12N-substituted matrinane derivatives were synthesized and evaluated for their activities against coxsackievirus type B3 (CVB3) taking compound 1 as the lead. SAR analysis indicated that the introduction of a suitable heteroaromatic ring on the 12N-atom might be beneficial for the activity. Among them, compound 8a exhibited the highest potency against all CVB serotypes as well as CVA16 with IC50 values ranging from 2.02 μM to 7.41 μM, indicating a broad-spectrum anti-coxsackieviruse effect. Furthermore, compound 8a demonstrated a good safety profile in vivo. Thus, we consider 12N-substituted matrinanes to be a promising family of anti-coxsackievirus agents, and compound 8a to be a promising drug candidate in the treatment of various diseases related to coxsackievirus infection.