Novel gamma-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates

Bioorg Med Chem Lett. 2006 Jul 15;16(14):3813-6. doi: 10.1016/j.bmcl.2006.04.025. Epub 2006 May 8.

Abstract

Screening of our in-house compound library comprised of intermediates of natural product synthesis projects resulted in discovering two novel gamma-secretase inhibitors, which coincidently had similar moieties, that is, cyclohexenone and two aryl groups arranged on the core six-membered ring. Structure-activity relationship studies of these compounds were also developed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases
  • Biological Products / chemistry*
  • Biological Products / pharmacology
  • Cyclohexanones / chemistry
  • Cyclohexanones / pharmacology
  • Dioxoles / chemistry
  • Endopeptidases / metabolism*
  • Heterocyclic Compounds / chemistry
  • Inhibitory Concentration 50
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Tacrolimus / chemistry
  • Tacrolimus / pharmacology
  • Tetrahydroisoquinolines / chemistry
  • Trabectedin
  • Vinblastine / chemistry
  • Vinblastine / pharmacology

Substances

  • Biological Products
  • Cyclohexanones
  • Dioxoles
  • Heterocyclic Compounds
  • Protease Inhibitors
  • Tetrahydroisoquinolines
  • Vinblastine
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Trabectedin
  • Tacrolimus