Abstract
We report the design, synthesis, and biological evaluation of a novel class of cannabinergic ligands, namely C1'-azacycloalkyl hexahydrocannabinols. Our synthetic approaches utilize an advanced common chiral intermediate triflate from which all analogues could be derived. Key synthetic steps involve microwave-assisted Liebeskind-Srogl C-C cross-coupling and palladium-catalyzed decarboxylative coupling reactions. The C1'-N-methylazetidinyl and C1'-N-methylpyrrolidinyl analogues were found to be high affinity ligands for the CB1 and CB2 cannabinoid receptors.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Cannabinol / analogs & derivatives*
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Cannabinol / chemical synthesis
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Cannabinol / chemistry
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Cannabinol / pharmacology
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Catalysis
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Dose-Response Relationship, Drug
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HEK293 Cells
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Humans
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Ligands
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Mice
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Molecular Conformation
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Palladium / chemistry
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Rats
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
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Receptor, Cannabinoid, CB2 / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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C1'-azacycloalkyl hexahydrocannabinol
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Ligands
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Receptor, Cannabinoid, CB1
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Receptor, Cannabinoid, CB2
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Palladium
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Cannabinol