Discovery of 7-(Prolinol-N-yl)-2-phenylamino-thiazolo[5,4-d]pyrimidines as Novel Non-Nucleoside Partial Agonists for the A2A Adenosine Receptor: Prediction from Molecular Modeling

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• 作者：Sandip B. Bharate ; Baljinder Singh ; Sonja Kachler ; Ana Oliveira ; Vikas Kumar ; Sonali S. Bharate ; Ram A. Vishwakarma ; Karl-Norbert Klotz ; Hugo Gutiérrez de Terán
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：June 23, 2016
• 年：2016
• 卷：59
• 期：12
• 页码：5922-5928
• 全文大小：428K
• 年卷期：0
• ISSN：1520-4804

文摘

We describe the identification of 7-(prolinol-N-yl)-2-phenylamino-thiazolo[5,4-d]pyrimidines as a novel chemotype of non-nucleoside partial agonists for the A_2A adenosine receptor (A_2AAR). Molecular-modeling indicated that the (S)-2-hydroxymethylene-pyrrolidine could mimic the interactions of agonists’ ribose, suggesting that this class of compounds could have agonistic properties. This was confirmed by functional assays on the A_2AAR, where their efficacy could be associated with the presence of the 2-hydroxymethylene moiety. Additionally, the best compound displays promising affinity, selectivity profile, and physicochemical properties.