N-(3-(4-Hydroxyphenyl)-propenoyl)-amino acid tryptamides as SIRT2 inhibitors

Bioorg Med Chem Lett. 2007 May 1;17(9):2448-51. doi: 10.1016/j.bmcl.2007.02.023. Epub 2007 Feb 13.

Abstract

A series of N-(3-(4-hydroxyphenyl)-propenoyl)-amino acid tryptamides was based on a previously reported new SIRT2 inhibitor from our group, and it was designed to study if the molecular size of the compound could be reduced. The most potent compounds, N-(3-(4-hydroxyphenyl)-propenoyl)-2-aminoisobutyric acid tryptamide and N-(3-(4-hydroxyphenyl)-propenoyl)-L-alanine tryptamide, were equipotent, 30% smaller in molecular weight, and slightly more selective (SIRT2/SIRT1) than the parent compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Molecular Structure
  • Molecular Weight
  • Niacinamide / analogs & derivatives*
  • Niacinamide / chemical synthesis
  • Niacinamide / pharmacology
  • Sirtuin 1
  • Sirtuin 2
  • Sirtuins / antagonists & inhibitors*
  • Tryptamines / chemical synthesis*
  • Tryptamines / pharmacology*

Substances

  • Tryptamines
  • Niacinamide
  • tryptamide
  • SIRT1 protein, human
  • SIRT2 protein, human
  • Sirtuin 1
  • Sirtuin 2
  • Sirtuins