Synthesis of two fluoro analogues of the nicotinic acetylcholine receptor agonist UB-165

J Org Chem. 2003 Mar 21;68(6):2475-8. doi: 10.1021/jo026698b.

Abstract

Two racemic fluoropyridine analogues 4 and 5 of the potent nicotinic agonist UB-165 have been synthesized. Halogenated pyridines 7 and 12 provided the organometallic reagents needed for the Negishi and Suzuki coupling reactions used for the preparation of 4 and 5, and the N-vinyloxycarbonyl protecting group of 8 and 15 was cleaved using a novel trifluoroacetic acid-mediated deprotection protocol. Analogue 4 retained high binding affinity at rat brain alpha4beta2 and alpha7 nicotinic receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / metabolism
  • Bridged-Ring Compounds / chemical synthesis*
  • Bridged-Ring Compounds / chemistry
  • Bridged-Ring Compounds / pharmacology
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Molecular Structure
  • Nicotinic Agonists / chemical synthesis*
  • Nicotinic Agonists / chemistry
  • Nicotinic Agonists / pharmacology
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Rats
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • (2-chloro-5-pyridyl)-9-azabicyclo(4.2.1)non-2-ene
  • Bridged-Ring Compounds
  • Chrna7 protein, rat
  • Hydrocarbons, Fluorinated
  • Nicotinic Agonists
  • Pyridines
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • nicotinic receptor alpha4beta2