Discovery of 7-Oxopyrazolo[1,5-a]pyrimidine-6-carboxamides as Potent and Selective CB2 Cannabinoid Receptor Inverse Agonists

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• 作者：Mojgan Aghazadeh Tabrizi ; Pier Giovanni Baraldi ; Giulia Saponaro ; Allan R. Moorman ; Romeo Romagnoli ; Delia Preti ; Stefania Baraldi ; Emanuela Ruggiero ; Cristina Tintori ; Tiziano Tuccinardi ; Fabrizio Vincenzi ; Pier Andrea Borea ; Katia Varani
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：June 13, 2013
• 年：2013
• 卷：56
• 期：11
• 页码：4482-4496
• 全文大小：498K
• 年卷期：v.56,no.11(June 13, 2013)
• ISSN：1520-4804

文摘

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.