Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4): Part I. Discovery of pyrazolo[3,4-d]pyrimidines as novel mGluR4 positive allosteric modulators

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5626-30. doi: 10.1016/j.bmcl.2008.08.087. Epub 2008 Aug 29.

Abstract

This letter describes the synthesis and SAR, developed through an iterative analogue library approach, of an mGluR4 positive allosteric modulator lead based on a pyrazolo[3,4-d]pyrimidine scaffold. Despite tremendous therapeutic potential, Compound 7, VU0080421, and related congeners represent only a handful of mGluR4 positive allosteric modulators ever described.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Animals
  • CHO Cells
  • Chemistry, Pharmaceutical / methods*
  • Cricetinae
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Drug Design
  • Glutamic Acid / chemistry
  • Models, Chemical
  • Neurotransmitter Agents / metabolism
  • Pyrimidines / chemistry*
  • Receptors, Metabotropic Glutamate / chemistry*
  • Receptors, Metabotropic Glutamate / metabolism
  • Structure-Activity Relationship

Substances

  • Neurotransmitter Agents
  • Pyrimidines
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid
  • pyrimidine
  • metabotropic glutamate receptor 4