A combined bioinformatics and chemoinformatics approach for developing asymmetric bivalent AMPA receptor positive allosteric modulators as neuroprotective agents

ChemMedChem. 2013 Feb;8(2):226-30. doi: 10.1002/cmdc.201200554. Epub 2012 Dec 20.

Abstract

PAMs new in town! An effective, combined bioinformatics and chemoinformatics approach was applied to the design of novel asymmetric bivalent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor positive allosteric modulators (PAMs) with marked potency in vitro and efficacy in vivo for preventing neuroapoptosis. The novel chemotype could provide pharmacological probes and potential therapeutic agents for glutamatergic hypofunction and its related neurological and psychiatric disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation / drug effects*
  • Animals
  • Apoptosis / drug effects
  • Computational Biology / methods
  • Drug Design*
  • Humans
  • Models, Molecular
  • Neurons / cytology
  • Neurons / drug effects
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Receptors, AMPA / agonists
  • Receptors, AMPA / metabolism*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / chemistry*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology*

Substances

  • Neuroprotective Agents
  • Receptors, AMPA
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid