Synthesis and biological evaluation of 2-substituted quinoline 6-carboxamides as potential mGluR1 antagonists for the treatment of neuropathic pain

Chem Pharm Bull (Tokyo). 2014;62(6):508-18. doi: 10.1248/cpb.c13-00945.

Abstract

A series of 2-amino and 2-methoxy quinoline-6-carboxamide derivatives have been synthesized and their metabotropic glutamate receptor type 1 (mGluR1) antagonistic activities were evaluated in a functional cell-based assay. The compound 13c showed the highest potency with IC50 value of 2.16 µM against mGluR1. Finally, in vivo evaluation of 13c in the rat spinal nerve ligation (SNL) model exhibited weak analgesic effects with regard to both mechanical allodynia and cold allodynia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cold Temperature
  • Dose-Response Relationship, Drug
  • Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
  • Humans
  • Hyperalgesia / drug therapy
  • Mice
  • Molecular Structure
  • Neuralgia / drug therapy*
  • Pain Measurement / drug effects
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Rats
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Ether-A-Go-Go Potassium Channels
  • N-ethyl-2-(piperidin-1-yl)quinoline-6-carboxamide
  • Piperidines
  • Quinolines
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1