Synthesis and SAR of alpha-acylaminoketone ligands for control of gene expression

Bioorg Med Chem Lett. 2003 Feb 10;13(3):475-8. doi: 10.1016/s0960-894x(02)00980-0.

Abstract

A lead discovery library and a follow-up focused library of alpha-acylaminoketones were designed based on known dibenzoylhydrazine ecdysone agonists, including GS(TM)-E. The compounds were assayed in mammalian cells expressing the ecdysone receptor from Bombyx mori for their ability to cause expression of a reporter gene downstream of an ecdysone response element. The most potent alpha-acylaminoketones were comparable to GS(TM)-E in this assay.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amines / chemical synthesis*
  • Amines / pharmacology*
  • Animals
  • Bombyx / metabolism
  • Cells, Cultured
  • Ecdysone / pharmacology
  • Gene Expression / drug effects*
  • Indicators and Reagents
  • Ketones / chemical synthesis*
  • Ketones / pharmacology*
  • Lethal Dose 50
  • Mice
  • Molecular Conformation
  • Receptors, Steroid / antagonists & inhibitors
  • Structure-Activity Relationship
  • beta-Galactosidase / biosynthesis
  • beta-Galactosidase / genetics

Substances

  • Amines
  • Indicators and Reagents
  • Ketones
  • Receptors, Steroid
  • ecdysone receptor
  • Ecdysone
  • beta-Galactosidase