Oxadiazole-carbonylaminothioureas as SIRT1 and SIRT2 inhibitors

J Med Chem. 2008 Aug 14;51(15):4377-80. doi: 10.1021/jm800639h. Epub 2008 Jul 22.

Abstract

A new inhibitor for human sirtuin type proteins 1 and 2 (SIRT1 and SIRT2) was discovered through virtual database screening in search of new scaffolds. A series of compounds was synthesized based on the hit compound (3-[[3-(4-tert-butylphenyl)1,2,4-oxadiazole-5-carbonyl]amino]-1-[3-(trifluoromethyl)phenyl]thiourea). The most potent compound in the series was nearly as potent as the reference compound (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology
  • Semicarbazides / chemical synthesis*
  • Semicarbazides / chemistry
  • Semicarbazides / pharmacology*
  • Sirtuin 1
  • Sirtuin 2
  • Sirtuins / antagonists & inhibitors*
  • Sirtuins / chemistry
  • Sirtuins / metabolism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Oxadiazoles
  • Semicarbazides
  • thiosemicarbazide
  • SIRT1 protein, human
  • SIRT2 protein, human
  • Sirtuin 1
  • Sirtuin 2
  • Sirtuins