2-(N-Acyl) and 2-N-acyl-N⁶-substituted analogues of adenosine and their affinity at the human adenosine receptors

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• 作者：Jagtap ; Prakash G. ; Chen ; Zhiyu ; Szab&oacute ; Csaba ; Klotz ; Karl-Norbert
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2004
• 出版时间：March 22, 2004
• 年：2004
• 卷：14
• 期：6
• 页码：1495-1498
• 全文大小：177 K

文摘

A series of 2-(N-acyl) and 2-(N-acyl)-N⁶-alkyladenosine analogues have been synthesized from the intermediate 2-amino-6-chloroadenosine derivatives (2b and 7) and evaluated for their affinity at the human A₁, A_2A, and A₃ receptors. We found that 2-(N-acyl) derivatives of adenosine showed relatively low affinity at A_2A and A₃ receptors, while the N⁶-cyclopentyl substituent in 4h and 4i induced high potency [A₁ (K_i)=20.7 and 31.8 nM respectively] at the A₁ receptor and resulted therefore in increased selectivity for this subtype. The general synthetic methods and their binding studies are presented herein.