7-Azaindole derivatives as potential partial nicotinic agonists

Bioorg Med Chem Lett. 2008 Jan 1;18(1):188-93. doi: 10.1016/j.bmcl.2007.10.101. Epub 2007 Nov 1.

Abstract

We have investigated a series of 7-azaindoles as potential partial agonists of the alpha4beta2 nicotinic acetylcholine receptor (nAChR). Three series of 7-azaindole derivatives have been synthesized and evaluated for rat brain neuronal nicotinic receptor affinity and functional activity. Compound (+)-51 exhibited the most potent nAChR binding (Ki = 10 nM). Compound 30A demonstrated both moderate binding affinity and partial agonist potency, thus representing a promising lead for the indications of cognition and smoking cessation.

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / metabolism
  • Animals
  • Aza Compounds / chemical synthesis
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacokinetics
  • Aza Compounds / pharmacology
  • Azocines / chemistry
  • Azocines / metabolism
  • Brain / metabolism
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacokinetics
  • Indoles / pharmacology*
  • Kinetics
  • Neurons / metabolism
  • Nicotinic Agonists / chemical synthesis
  • Nicotinic Agonists / chemistry*
  • Nicotinic Agonists / pharmacokinetics
  • Nicotinic Agonists / pharmacology*
  • Quinolizines / chemistry
  • Quinolizines / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / metabolism

Substances

  • 7-azaindole dimer
  • Alkaloids
  • Aza Compounds
  • Azocines
  • Indoles
  • Nicotinic Agonists
  • Quinolizines
  • Receptors, Nicotinic
  • nicotinic receptor alpha4beta2
  • cytisine