Abstract
Quinoline, isoquinoline, quinoxaline, and quinazoline derivatives were synthesized using microwave-assisted synthesis and their CB1/CB2 receptor activities were determined using the [³⁵S]GTPγS binding assay. Most of the prepared quinoline, isoquinoline, and quinoxalinyl phenyl amines showed low-potency partial CB2 receptor agonists activity. The most potent CB2 ligand was the 4-morpholinylmethanone derivative (compound 40e) (-log EC₅₀ = 7.8; E(max) = 75%). The isoquinolin-1-yl(3-trifluoromethyl-phenyl)amine (compound 26c) was a high efficacy CB2 agonist (-log EC₅₀ = 5.8; E(max) = 128%). No significant CB1 receptor activation or inactivation was shown in these studies, except 40e, which showed weak CB1 agonist activity (CB1 -log EC₅₀ = 5.0). These ligands serve as novel templates for the development of selective CB2 receptor agonist.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Isoquinolines / chemical synthesis*
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Isoquinolines / chemistry*
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Isoquinolines / pharmacology
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Microwaves*
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Morpholines / chemical synthesis*
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Morpholines / chemistry
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Morpholines / pharmacology
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Quinazolines / chemical synthesis
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Quinazolines / chemistry*
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Quinazolines / pharmacology
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / pharmacology
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Quinoxalines / chemical synthesis
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Quinoxalines / chemistry*
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Quinoxalines / pharmacology
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Receptor, Cannabinoid, CB1 / agonists
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Receptor, Cannabinoid, CB1 / metabolism
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Receptor, Cannabinoid, CB2 / agonists*
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Receptor, Cannabinoid, CB2 / metabolism
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Structure-Activity Relationship
Substances
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Isoquinolines
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Morpholines
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N-(morpholinyl)-1-(3-(trifluoromethyl)phenylamino)isoquinoline-4-carboxamide
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Quinazolines
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Quinolines
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Quinoxalines
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Receptor, Cannabinoid, CB1
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Receptor, Cannabinoid, CB2
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quinoline
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isoquinoline