The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist.

Michael Moir; Samuel  Lane; Andrew P. Montgomery; David Hibbs; Mark Connor; Michael Kassiou

doi:10.1016/j.ejmech.2020.113087

The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist.

Michael Moir, Samuel Lane, Andrew P. Montgomery, David Hibbs, Mark Connor, Michael Kassiou

Faculty of Medicine, Health and Human Sciences

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

3 Citations (Scopus)

Abstract

The development of selective CB₂ receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB₁ receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB₂R EC₅₀ = 19 nM, CB₁R EC₅₀ > 10 μM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.

Original language	English
Article number	113087
Pages (from-to)	1-28
Number of pages	28
Journal	European Journal of Medicinal Chemistry
Volume	210
DOIs	https://doi.org/10.1016/j.ejmech.2020.113087
Publication status	Published - 15 Jan 2021

Keywords

CB(2)R selective;
Cannabinoid
Docking
Pyrazolotriazine
Structure-activity relationship study
Synthesis
CB R selective

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title = "The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist.",

abstract = "The development of selective CB2 receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB1 receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB2R EC50 = 19 nM, CB1R EC50 > 10 μM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.",

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AU - Moir, Michael

AU - Lane, Samuel

AU - Montgomery, Andrew P.

AU - Hibbs, David

AU - Connor, Mark

AU - Kassiou, Michael

PY - 2021/1/15

Y1 - 2021/1/15

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AB - The development of selective CB2 receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB1 receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB2R EC50 = 19 nM, CB1R EC50 > 10 μM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.

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KW - Docking

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KW - Structure-activity relationship study

KW - Synthesis

KW - CB R selective

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The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist.

Abstract

Keywords

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