3-(Imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers: a novel series of mGluR2 positive allosteric modulators

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5493-6. doi: 10.1016/j.bmcl.2008.09.026. Epub 2008 Sep 10.

Abstract

The synthesis and structure-activity relationship (SAR) of a novel series of 3-(imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers, derived from a high throughput screening (HTS), are described. Subsequent optimization led to identification of potent, metabolically stable and orally available mGluR2 positive allosteric modulators (PAMs).

MeSH terms

  • Administration, Oral
  • Allosteric Regulation*
  • Allosteric Site
  • Animals
  • Azabicyclo Compounds / chemical synthesis*
  • Azabicyclo Compounds / pharmacology
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / pharmacology
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Drug Evaluation, Preclinical
  • Ethers / chemistry*
  • Humans
  • Microsomes / drug effects
  • Models, Chemical
  • Rats
  • Receptors, Metabotropic Glutamate / chemistry*
  • Schizophrenia / drug therapy
  • Structure-Activity Relationship

Substances

  • Azabicyclo Compounds
  • Benzimidazoles
  • Ethers
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2