Abstract
We recently described the medicinal chemistry of a new series of heteroaryl-4-oxopyridine/7-oxopyrimidines as CB2 receptor partial agonists, showing that the functionality of these ligands is controlled by the nature of the heteroaryl function condensed with the pyridine ring. We describe herein the design and synthesis of the 7-oxopyrazolo[1,5-a]pyrimidine-6-carboxamides, structural isomers of our previously reported pyrazolo[3,4-b]pyridines. All of the new compounds showed high affinity and selectivity for the CB2 receptor in the nanomolar range. In 3,5-cyclic adenosine monophosphate (cAMP) assays, the novel series shows stimulatory effects on forskolin-induced cAMP production acting as inverse agonists.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Binding, Competitive
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CHO Cells
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Cricetinae
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Cricetulus
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Cyclic AMP / biosynthesis
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Drug Inverse Agonism
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Humans
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Male
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Models, Molecular
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Pyrazoles / chemical synthesis*
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Pyrazoles / chemistry
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Pyrazoles / pharmacology
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptor, Cannabinoid, CB1 / metabolism
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Receptor, Cannabinoid, CB2 / agonists
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Receptor, Cannabinoid, CB2 / antagonists & inhibitors
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Receptor, Cannabinoid, CB2 / metabolism*
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Structure-Activity Relationship
Substances
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Amides
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Anti-Inflammatory Agents, Non-Steroidal
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Pyrazoles
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Pyrimidines
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Receptor, Cannabinoid, CB1
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Receptor, Cannabinoid, CB2
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Cyclic AMP