Synthesis and SAR of cis-1-benzoyl-1,2,3,4-tetrahydroquinoline ligands for control of gene expression in ecdysone responsive systems

Bioorg Med Chem Lett. 2003 Jun 2;13(11):1943-6. doi: 10.1016/s0960-894x(03)00317-2.

Abstract

A library of 35 cis-1-benzoyl-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolines was prepared. The compounds bore various substitutuents on the benzoyl ring, at the 4-position of the phenylamino ring and at the 6-position of the tetrahydroquinoline ring. The compounds were assayed for their ability to cause expression of a reporter gene downstream of an ecdysone response element in a mammalian cell line engineered to express the ecdysone receptor from Aedes aegypti. In general, compounds with small lipophilic substituents at the meta and para-positions of the benzoyl ring and hydrogen or fluorine at the 4-position of the phenylamino ring and the 6-position of the tetrahydroquinoline ring were the most potent.

Publication types

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

MeSH terms

  • Aedes / metabolism
  • Animals
  • Dose-Response Relationship, Drug
  • Ecdysone / genetics
  • Ecdysone / metabolism*
  • Gene Expression Regulation / drug effects*
  • Isomerism
  • Ligands
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Receptors, Steroid / drug effects
  • Receptors, Steroid / metabolism
  • Structure-Activity Relationship
  • Transcriptional Activation / drug effects

Substances

  • Ligands
  • Quinolines
  • Receptors, Steroid
  • ecdysone receptor
  • Ecdysone