Identification of novel alpha7 nAChR positive allosteric modulators with the use of pharmacophore in silico screening methods

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4561-5. doi: 10.1016/j.bmcl.2010.06.014. Epub 2010 Jun 8.

Abstract

The pharmacophore model of in house potent and selective alpha7 nAChR positive allosteric modulators is reported. The model was used to fish out commercially-available compounds from corporate 3D databases. As a result, novel alpha7 positive modulator chemotypes were identified. A rat full PK profile of a representative compound is also described.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Animals
  • Cell Line
  • Databases, Factual
  • Humans
  • Isoxazoles / chemistry
  • Isoxazoles / pharmacokinetics
  • Microsomes, Liver / metabolism
  • Models, Molecular
  • Phenylurea Compounds / chemistry
  • Phenylurea Compounds / pharmacokinetics
  • Rats
  • Receptors, Nicotinic / chemistry*
  • Receptors, Nicotinic / metabolism
  • Structure-Activity Relationship
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)urea
  • Chrna7 protein, human
  • Chrna7 protein, rat
  • Isoxazoles
  • Phenylurea Compounds
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor