Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists

Hoang Nam Vu; Ji Young Kim; Ahmed H.E. Hassan; Kihang Choi; Jong Hyun Park; Ki Duk Park; Jae Kyun Lee; Ae Nim Pae; Hyunah Choo; Sun Joon Min; Yong Seo Cho

doi:10.1016/j.bmcl.2015.11.012

Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists

Hoang Nam Vu, Ji Young Kim, Ahmed H.E. Hassan, Kihang Choi, Jong Hyun Park, Ki Duk Park, Jae Kyun Lee, Ae Nim Pae, Hyunah Choo, Sun Joon Min, Yong Seo Cho

Department of Chemistry

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

7 Citations (Scopus)

Abstract

We described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC₅₀ = 274 and 159 nM) showing excellent in vitro stability profile. Molecular docking study using the crystal structure of mGluR5 revealed that our compounds 6bc and 6bj fit the allosteric binding site of mavoglurant well.

Original language	English
Pages (from-to)	140-144
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	26
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2015.11.012
Publication status	Published - 2016 Jan 1

Keywords

Antagonist
Metabotropic glutamate receptor
Molecular docking
Picolinamides
Thiazole-2-carboxamides

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.2015.11.012

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Vu, H. N., Kim, J. Y., Hassan, A. H. E., Choi, K., Park, J. H., Park, K. D., Lee, J. K., Pae, A. N., Choo, H., Min, S. J., & Cho, Y. S. (2016). Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists. Bioorganic and Medicinal Chemistry Letters, 26(1), 140-144. https://doi.org/10.1016/j.bmcl.2015.11.012

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title = "Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists",

abstract = "We described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC50 = 274 and 159 nM) showing excellent in vitro stability profile. Molecular docking study using the crystal structure of mGluR5 revealed that our compounds 6bc and 6bj fit the allosteric binding site of mavoglurant well.",

keywords = "Antagonist, Metabotropic glutamate receptor, Molecular docking, Picolinamides, Thiazole-2-carboxamides",

author = "Vu, {Hoang Nam} and Kim, {Ji Young} and Hassan, {Ahmed H.E.} and Kihang Choi and Park, {Jong Hyun} and Park, {Ki Duk} and Lee, {Jae Kyun} and Pae, {Ae Nim} and Hyunah Choo and Min, {Sun Joon} and Cho, {Yong Seo}",

note = "Funding Information: This research was supported by the Korea Institute of Science and Technology (KIST, 2E25580 , 2E25473 , 2E25240 , 2V03970 ) and by a Grant of the National Research Foundation of Korea ( NRF-2013R1A1A2005550 and NRF-2015M3A9A8030034 ) funded by the Ministry of Science, ICT and Future Planning . Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd. All rights reserved.",

year = "2016",

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doi = "10.1016/j.bmcl.2015.11.012",

language = "English",

volume = "26",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists

AU - Vu, Hoang Nam

AU - Kim, Ji Young

AU - Hassan, Ahmed H.E.

AU - Choi, Kihang

AU - Park, Jong Hyun

AU - Park, Ki Duk

AU - Lee, Jae Kyun

AU - Pae, Ae Nim

AU - Choo, Hyunah

AU - Min, Sun Joon

AU - Cho, Yong Seo

N1 - Funding Information: This research was supported by the Korea Institute of Science and Technology (KIST, 2E25580 , 2E25473 , 2E25240 , 2V03970 ) and by a Grant of the National Research Foundation of Korea ( NRF-2013R1A1A2005550 and NRF-2015M3A9A8030034 ) funded by the Ministry of Science, ICT and Future Planning . Publisher Copyright: © 2015 Elsevier Ltd. All rights reserved.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - We described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC50 = 274 and 159 nM) showing excellent in vitro stability profile. Molecular docking study using the crystal structure of mGluR5 revealed that our compounds 6bc and 6bj fit the allosteric binding site of mavoglurant well.

AB - We described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC50 = 274 and 159 nM) showing excellent in vitro stability profile. Molecular docking study using the crystal structure of mGluR5 revealed that our compounds 6bc and 6bj fit the allosteric binding site of mavoglurant well.

KW - Antagonist

KW - Metabotropic glutamate receptor

KW - Molecular docking

KW - Picolinamides

KW - Thiazole-2-carboxamides

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IS - 1

ER -

Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists

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