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

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

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1472-1476
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2012.12.056
Publication status	Published - 2013 Mar 1

Keywords

Antagonist
Metabotropic glutamate receptor
Neuropathic pain
Quinoline
Sonogashira reaction

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2012.12.056

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

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.",

keywords = "Antagonist, Metabotropic glutamate receptor, Neuropathic pain, Quinoline, Sonogashira reaction",

author = "Son, {Myung Hee} and Kim, {Ji Young} and Lim, {Eun Jeong} and Baek, {Du Jong} and Kihang Choi and Lee, {Jae Kyun} and Pae, {Ae Nim} and Min, {Sun Joon} and Cho, {Yong Seo}",

note = "Funding Information: This research was supported by the Korea Institute of Science and Technology (KIST) and by a grant of the Korea Health technology R&D Project, the Ministry of Health and Welfare, Republic of Korea (A111035). ",

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doi = "10.1016/j.bmcl.2012.12.056",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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AU - Son, Myung Hee

AU - Kim, Ji Young

AU - Lim, Eun Jeong

AU - Baek, Du Jong

AU - Choi, Kihang

AU - Lee, Jae Kyun

AU - Pae, Ae Nim

AU - Min, Sun Joon

AU - Cho, Yong Seo

N1 - Funding Information: This research was supported by the Korea Institute of Science and Technology (KIST) and by a grant of the Korea Health technology R&D Project, the Ministry of Health and Welfare, Republic of Korea (A111035).

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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.

AB - 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.

KW - Antagonist

KW - Metabotropic glutamate receptor

KW - Neuropathic pain

KW - Quinoline

KW - Sonogashira reaction

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U2 - 10.1016/j.bmcl.2012.12.056

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AN - SCOPUS:84873744551

SN - 0960-894X

VL - 23

SP - 1472

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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