Structure activity studies of ring E analogues of methyllycaconitine. Part 2: Synthesis of antagonists to the alpha3beta4* nicotinic acetylcholine receptors through modifications to the ester

Bioorg Med Chem Lett. 2004 Jul 16;14(14):3739-42. doi: 10.1016/j.bmcl.2004.05.001.

Abstract

The development of novel agents for the differentiation of neuronal nicotinic acetylcholine receptors (nAChRs) is important for the treatment of a variety of pathological conditions. We have prepared and evaluated a number of simpler analogues of the norditerpeniod alkaloid methyllycaconitine (MLA) in an effort to understand molecular determinants of nAChR*small molecule interactions. We have previously reported the synthesis and evaluation of a series of ring E analogues of MLA. We report here the optimization of the alpha3beta4* functional activity of this series of compounds through modification of the ester.

Publication types

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

MeSH terms

  • Aconitine / analogs & derivatives*
  • Aconitine / chemical synthesis*
  • Aconitine / pharmacology
  • Alkaloids / chemical synthesis
  • Alkaloids / pharmacology
  • Animals
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Catecholamines / metabolism
  • Cell Line
  • Diterpenes / chemical synthesis
  • Diterpenes / pharmacology
  • Esters / chemistry
  • Nicotinic Antagonists / chemical synthesis*
  • Nicotinic Antagonists / pharmacology
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / metabolism
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Catecholamines
  • Diterpenes
  • Esters
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • nicotinic receptor alpha3beta4
  • methyllycaconitine
  • Aconitine