Nitrogen-appended N-alkylsulfonamides as inhibitors of gamma-secretase

Bioorg Med Chem Lett. 2008 Jan 1;18(1):175-8. doi: 10.1016/j.bmcl.2007.10.105. Epub 2007 Nov 1.

Abstract

The synthesis and gamma-secretase inhibition data for a series of nitrogen-appended N-alkylsulfonamides (11-47) are described. Inhibition of brain Abeta in transgenic mice was demonstrated by two of these compounds (23 and 44).

MeSH terms

  • Alkylation
  • Amines / chemical synthesis
  • Amines / chemistry*
  • Amines / pharmacology*
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Azoles / chemical synthesis
  • Azoles / chemistry
  • Azoles / pharmacology
  • Brain / drug effects
  • Brain / enzymology
  • Brain / metabolism
  • Hydrophobic and Hydrophilic Interactions
  • Inhibitory Concentration 50
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / metabolism
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*

Substances

  • Amines
  • Amyloid beta-Peptides
  • Azoles
  • Peptide Fragments
  • Protease Inhibitors
  • Sulfonamides
  • amyloid beta-protein (1-40)
  • Amyloid Precursor Protein Secretases