New positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2): identification and synthesis of N-propyl-8-chloro-6-substituted isoquinolones

Bioorg Med Chem Lett. 2011 Feb 1;21(3):971-6. doi: 10.1016/j.bmcl.2010.12.048. Epub 2010 Dec 21.

Abstract

A series of N-propyl-8-chloro-6-substituted isoquinolones was identified as positive allosteric modulators of metabotropic glutamate receptor 2 (mGluR2 PAM) via high throughput screening (HTS). The subsequent synthesis and initial SAR exploration that led to the identification of compound 28 is described.

MeSH terms

  • Allosteric Regulation
  • High-Throughput Screening Assays
  • Humans
  • Microsomes, Liver / metabolism
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Quinolones / chemical synthesis
  • Quinolones / chemistry*
  • Quinolones / pharmacology
  • Receptors, Metabotropic Glutamate / chemistry*
  • Receptors, Metabotropic Glutamate / metabolism
  • Structure-Activity Relationship

Substances

  • Pyridines
  • Quinolones
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2