Synthesis and Biological Evaluation of 2-Substituted Quinoline 6-Carboxamides as Potential mGluR1 Antagonists for the Treatment of Neuropathic Pain

Younghee Kim; Jiwon Son; Juhyeon Kim; Du-Jong Baek; Yong Sup Lee; Eun Jeong Lim; Jae Kyun Lee; Ae Nim Pae; Sun-Joon Min; Yong Seo Cho

doi:10.1248/cpb.c13-00945

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Synthesis and Biological Evaluation of 2-Substituted Quinoline 6-Carboxamides as Potential mGluR1 Antagonists for the Treatment of Neuropathic Pain

Younghee Kim, Jiwon Son, Juhyeon Kim, Du-Jong Baek, Yong Sup Lee, Eun Jeong Lim, Jae Kyun Lee, Ae Nim Pae, Sun-Joon Min , Yong Seo Cho

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Keywords: glutamate, metabotropic glutamate receptor (mGluR), quinoline, neuropathic pain, spinal nerve ligation (SNL) model

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2014 Volume 62 Issue 6 Pages 508-518

DOI https://doi.org/10.1248/cpb.c13-00945

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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.

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