Biphenyl-indanones: allosteric potentiators of the metabotropic glutamate subtype 2 receptor

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4354-8. doi: 10.1016/j.bmcl.2005.06.062.

Abstract

We have identified and synthesized a series of biphenyl-carboxylic acid indanones as allosteric potentiators of the metabotropic glutamate receptor 2. Structure-activity relationship studies directed toward improving the potency and the brain to plasma ratio of the initial lead led to the discovery of 5 and 23 (EC50=111 and 5 nM, respectively).

MeSH terms

  • Allosteric Regulation
  • Animals
  • Biphenyl Compounds / chemical synthesis*
  • Biphenyl Compounds / metabolism
  • Biphenyl Compounds / pharmacokinetics
  • Brain Chemistry
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Humans
  • Indans / chemical synthesis*
  • Indans / metabolism
  • Indans / pharmacokinetics
  • Rats
  • Receptors, Metabotropic Glutamate / agonists*
  • Receptors, Metabotropic Glutamate / metabolism
  • Schizophrenia / drug therapy
  • Structure-Activity Relationship
  • Tissue Distribution

Substances

  • Biphenyl Compounds
  • Indans
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • Guanosine 5'-O-(3-Thiotriphosphate)