Synthesis and biological evaluation of 2-(arylethynyl)quinoline derivatives as mGluR5 antagonists for the treatment of neuropathic pain

Myung-Hee Son; Ji Young Kim; Eun Jeong Lim; Du-Jong Baek; Kihang Choi; Jae Kyun Lee; Ae Nim Pae; Sun-Joon Min; Yong Seo Cho

doi:10.1016/j.bmcl.2012.12.056

Synthesis and biological evaluation of 2-(arylethynyl)quinoline derivatives as mGluR5 antagonists for the treatment of neuropathic pain

Bioorg Med Chem Lett. 2013 Mar 1;23(5):1472-6. doi: 10.1016/j.bmcl.2012.12.056. Epub 2012 Dec 22.

Authors

Myung-Hee Son¹, Ji Young Kim, Eun Jeong Lim, Du-Jong Baek, Kihang Choi, Jae Kyun Lee, Ae Nim Pae, Sun-Joon Min, Yong Seo Cho

Affiliation

¹ Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.

PMID: 23333207
DOI: 10.1016/j.bmcl.2012.12.056

Abstract

We described here the synthesis and biological evaluation of mGluR5 antagonists containing a quinoline ring structure. Using intracellular calcium mobilization assay (FDSS assay), we identified compound 5n, showing high inhibitory activity against mGluR5. In addition, it was found that compound 5n has excellent stability profile. Finally, this compound exhibited favorable analgesic effects in spinal nerve ligation model of neuropathic pain, which is comparable to gabapentin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylene / analogs & derivatives*
Acetylene / chemistry
Acetylene / pharmacology
HEK293 Cells
Humans
Neuralgia / drug therapy*
Quinolines / chemical synthesis*
Quinolines / chemistry
Quinolines / pharmacology*
Receptor, Metabotropic Glutamate 5 / antagonists & inhibitors*

Substances

Quinolines
Receptor, Metabotropic Glutamate 5
Acetylene