N,N'-Bisbenzylidenebenzene-1,4-diamines and N,N'-Bisbenzylidenenaphthalene-1,4-diamines as Sirtuin Type 2 (SIRT2) Inhibitors

J Med Chem. 2006 Dec 28;49(26):7907-11. doi: 10.1021/jm060566j.

Abstract

A series of N,N'-bisbenzylidenebenzene-1,4-diamine and N,N'-bisbenzylidenenaphthalene-1,4-diamine derivatives were synthesized as inhibitors for human sirtuin type 2 (SIRT2). The design of the new compounds was based on two earlier reported hits from molecular modeling and virtual screening. The most potent compound was N,N'-bis(2-hydroxybenzylidene)benzene-1,4-diamine, which was equipotent with the most potent hit compound and well-known SIRT2 inhibitor sirtinol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Binding Sites
  • Diamines / chemical synthesis
  • Diamines / chemistry
  • Diamines / pharmacology*
  • Humans
  • Molecular Structure
  • Phenylenediamines / chemical synthesis
  • Phenylenediamines / chemistry
  • Phenylenediamines / pharmacology*
  • Sirtuin 2
  • Sirtuins / antagonists & inhibitors*
  • Sirtuins / metabolism
  • Structure-Activity Relationship

Substances

  • Diamines
  • N,N'-bis(2-hydroxybenzylidene)benzene-1,4-diamine
  • Phenylenediamines
  • SIRT2 protein, human
  • Sirtuin 2
  • Sirtuins