1,2,3-Triazole derivatives as new cannabinoid CB1 receptor antagonists

Duen Ren Hou; Safiul Alam; Ting Chun Kuan; Mani Ramanathan; Tsung Pang Lin; Ming Shiu Hung

doi:10.1016/j.bmcl.2008.11.029

1,2,3-Triazole derivatives as new cannabinoid CB1 receptor antagonists

Duen Ren Hou, Safiul Alam, Ting Chun Kuan, Mani Ramanathan, Tsung Pang Lin, Ming Shiu Hung

Department of Chemistry

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

60 Scopus citations

Abstract

This letter reports the new entry of novel 1,2,3-triazole derivatives as CB1 receptor antagonists. The design, synthesis and biological evaluation of N1 and N2 substituted 1,2,3-trizoles are described. The N2 substituted, symmetrical 1,2,3-triazoles are more potent ligands than the unsymmetrical analogues. The in vitro activity of these triazoles is further improved by inserting a methylene group between the central core and the carbonyl side chain. The most potent antagonists prepared in this series (IC₅₀ < 20 nM) are the triazoles containing benzyl amides. These triazoles also show excellent selectivity between CB1 and CB2 receptors (IC₅₀ > 10 μM for CB2; CB2/CB1 > 1000).

Original language	English
Pages (from-to)	1022-1025
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2008.11.029
State	Published - 1 Feb 2009

Keywords

Cannabinoid
Obesity
Triazole

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10.1016/j.bmcl.2008.11.029

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title = "1,2,3-Triazole derivatives as new cannabinoid CB1 receptor antagonists",

abstract = "This letter reports the new entry of novel 1,2,3-triazole derivatives as CB1 receptor antagonists. The design, synthesis and biological evaluation of N1 and N2 substituted 1,2,3-trizoles are described. The N2 substituted, symmetrical 1,2,3-triazoles are more potent ligands than the unsymmetrical analogues. The in vitro activity of these triazoles is further improved by inserting a methylene group between the central core and the carbonyl side chain. The most potent antagonists prepared in this series (IC50 < 20 nM) are the triazoles containing benzyl amides. These triazoles also show excellent selectivity between CB1 and CB2 receptors (IC50 > 10 μM for CB2; CB2/CB1 > 1000).",

keywords = "Cannabinoid, Obesity, Triazole",

author = "Hou, {Duen Ren} and Safiul Alam and Kuan, {Ting Chun} and Mani Ramanathan and Lin, {Tsung Pang} and Hung, {Ming Shiu}",

note = "Funding Information: This research was supported by the National Science Council (NSC 95-2323-B-007-005, NSC 96-2323-B-007-001 and NSC 95-2133-M-008-007-MY3), and National Health Research Institutes (NHRI), Taiwan, ROC. We are grateful to Ms. Ping-Yu Lin at the Institute of Chemistry, Academia Sinica, Ms. Wen-Chi Hsiao at NHRI, and Valuable Instrument Center in National Central University for obtaining mass analysis. ",

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AU - Hou, Duen Ren

AU - Alam, Safiul

AU - Kuan, Ting Chun

AU - Ramanathan, Mani

AU - Lin, Tsung Pang

AU - Hung, Ming Shiu

N1 - Funding Information: This research was supported by the National Science Council (NSC 95-2323-B-007-005, NSC 96-2323-B-007-001 and NSC 95-2133-M-008-007-MY3), and National Health Research Institutes (NHRI), Taiwan, ROC. We are grateful to Ms. Ping-Yu Lin at the Institute of Chemistry, Academia Sinica, Ms. Wen-Chi Hsiao at NHRI, and Valuable Instrument Center in National Central University for obtaining mass analysis.

PY - 2009/2/1

Y1 - 2009/2/1

N2 - This letter reports the new entry of novel 1,2,3-triazole derivatives as CB1 receptor antagonists. The design, synthesis and biological evaluation of N1 and N2 substituted 1,2,3-trizoles are described. The N2 substituted, symmetrical 1,2,3-triazoles are more potent ligands than the unsymmetrical analogues. The in vitro activity of these triazoles is further improved by inserting a methylene group between the central core and the carbonyl side chain. The most potent antagonists prepared in this series (IC50 < 20 nM) are the triazoles containing benzyl amides. These triazoles also show excellent selectivity between CB1 and CB2 receptors (IC50 > 10 μM for CB2; CB2/CB1 > 1000).

AB - This letter reports the new entry of novel 1,2,3-triazole derivatives as CB1 receptor antagonists. The design, synthesis and biological evaluation of N1 and N2 substituted 1,2,3-trizoles are described. The N2 substituted, symmetrical 1,2,3-triazoles are more potent ligands than the unsymmetrical analogues. The in vitro activity of these triazoles is further improved by inserting a methylene group between the central core and the carbonyl side chain. The most potent antagonists prepared in this series (IC50 < 20 nM) are the triazoles containing benzyl amides. These triazoles also show excellent selectivity between CB1 and CB2 receptors (IC50 > 10 μM for CB2; CB2/CB1 > 1000).

KW - Cannabinoid

KW - Obesity

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DO - 10.1016/j.bmcl.2008.11.029

M3 - 期刊論文

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AN - SCOPUS:58549117673

SN - 0960-894X

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 3

ER -

1,2,3-Triazole derivatives as new cannabinoid CB1 receptor antagonists

Abstract

Keywords

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