Synthesis and Pharmacological Evaluation of Dual Acting Antioxidant A2A Adenosine Receptor Agonists

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• 作者：Nicholas E. Hausler ; Shane M. Devine ; Fiona M. McRobb ; Lyndon Warfe ; Colin W. Pouton ; John M. Haynes ; Steven E. Bottle ; Paul J. White ; Peter J. Scammells
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：April 12, 2012
• 年：2012
• 卷：55
• 期：7
• 页码：3521-3534
• 全文大小：572K
• 年卷期：v.55,no.7(April 12, 2012)
• ISSN：1520-4804

文摘

A series of adenosine-5鈥?N-alkylcarboxamides and N⁶-(2,2-diphenylethyl)adenosine-5鈥?N-alkylcarboxamides bearing antioxidant moieties in the 2-position were synthesized from the versatile intermediate, O⁶-(benzotriazol-1-yl)-2-fluoro-2鈥?3鈥?O-isopropylideneinosine-5鈥?N-alkylcarboxamide (1). These compounds were evaluated as A_2A adenosine receptor (A_2AR) agonists in a cAMP accumulation assay, and a number of potent and selective agonists were identified. Three of these compounds were evaluated further in an ischemic injury cell survival assay and a reactive oxygen species (ROS) production assay whereby 15b and 15c were shown to reduce ROS activity and cell death due to ischemia.