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. Epub 2013 Jul 3.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoptosis / drug effects*
  • Carbazoles / chemistry*
  • Carbazoles / pharmacology*
  • Cell Survival / drug effects
  • Humans
  • Necrosis / drug therapy*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Structure-Activity Relationship

Substances

  • Carbazoles
  • Pyrazoles