A novel necroptosis inhibitor-necrostatin-21 and its SAR study

  • Bioorg Med Chem Lett. 2013 Sep 1;23(17):4903-6. doi: 10.1016/j.bmcl.2013.06.073.
Zhijie Wu  1 ,  Ying Li ,  Yu Cai ,  Junying Yuan ,  Chengye Yuan
Affiliations
  • 1. State Key Laboratory of Bio-organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
PMID: 23886688 DOI: 10.1016/j.bmcl.2013.06.073
Abstract

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 17 b was 35-fold as potent as the lead, while EC50 reached 14 nM.

Keywords
Inhibitor; JNK3; Nec-21; Necroptosis; RIP1; SAR study.
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