Design and synthesis of a novel series of (1'S,2R,4'S)-3H-4'-azaspiro[benzo[4,5]imidazo[2,1-b]oxazole-2,2'-bicyclo[2.2.2]octanes] with high affinity for the α7 neuronal nicotinic receptor

Bioorg Med Chem Lett. 2017 Nov 15;27(22):5002-5005. doi: 10.1016/j.bmcl.2017.10.009. Epub 2017 Oct 10.

Abstract

We describe an efficient and convergent synthesis of a series of (1'S,2R,4'S)-3H-4'-azaspiro[benzo[4,5]imidazo[2,1-b]oxazole-2,2'-bicyclo[2.2.2]octanes] displaying potency for the α7 nicotinic acetylcholine receptor (nAChR) and good selectivity vs. the related 5-HT3A receptor.

Keywords: 5-HT(3A) receptor; Schizophrenia; Spirooxazolines; α7 nicotinic acetylcholine receptor.

MeSH terms

  • Bridged Bicyclo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / chemistry
  • Bridged Bicyclo Compounds / metabolism*
  • Crystallography, X-Ray
  • Drug Design*
  • Humans
  • Hydrogen Bonding
  • Molecular Conformation
  • Nicotinic Agonists / chemistry
  • Nicotinic Agonists / metabolism
  • Octanes / chemical synthesis
  • Octanes / chemistry
  • Octanes / metabolism*
  • Protein Binding
  • Receptors, Serotonin, 5-HT3 / chemistry
  • Receptors, Serotonin, 5-HT3 / metabolism
  • Stereoisomerism
  • alpha7 Nicotinic Acetylcholine Receptor / chemistry
  • alpha7 Nicotinic Acetylcholine Receptor / metabolism*

Substances

  • Bridged Bicyclo Compounds
  • Nicotinic Agonists
  • Octanes
  • Receptors, Serotonin, 5-HT3
  • alpha7 Nicotinic Acetylcholine Receptor
  • bicyclo(2.2.2)octane