A novel necroptosis inhibitor¡ªnecrostatin-21 and its SAR study

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• 作者：Zhijie Wu ; Ying Li ; Yu Cai ; Junying Yuan ; Chengye Yuan
• 关键词：Necroptosis ; Nec-21 ; Inhibitor ; SAR study ; RIP1 ; JNK3
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 September, 2013
• 年：2013
• 卷：23
• 期：17
• 页码：4903-4906
• 全文大小：927 K

文摘

An initial structure-activity relationship study of the novel necroptosis inhibitor Nec-21 was described. Any changes of the tetracyclic scaffold were detrimental for the activity. Introduction of a substituent to 7 or 8 position (e.g., cyano or methoxy group, respectively), would increase the activity. The 7 and 8-position disubstituted compound 17b was 35-fold as potent as the lead, while EC₅₀ reached 14 nM.