New 2,6,9-trisubstituted adenines as adenosine receptor antagonists: a preliminary SAR profile

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• 作者：Catia Lambertucci ; Gloria Cristalli ; Diego Dal Ben ; Dhuldeo D. Kachare ; Chiara Bolcato ; Karl-Norbert Klotz ; Giampiero Spalluto and Rosaria Volpini
• 关键词：Adenine derivatives ; Adenosine receptors ; Adenosine receptor antagonists ; Adenosine receptor ligands ; G protein ; coupled receptors
• 刊名：Purinergic Signalling
• 出版年：2007
• 出版时间：September, 2007
• 年：2007
• 卷：3
• 期：4
• 页码：339-346
• 全文大小：220.8 KB

文摘

A new series of 2,6,9-trisubstituted adenines (5–14) have been prepared and evaluated in radioligand binding studies for their affinity at the human A₁, A_2A and A₃ adenosine receptors and in adenylyl cyclase experiments for their potency at the human A_2B subtype. From this preliminary study the conclusion can be drawn that introduction of bulky chains at the N 6 position of 9-propyladenine significantly increased binding affinity at the human A₁ and A₃ adenosine receptors, while the presence of a chlorine atom at the 2 position resulted in a not univocal effect, depending on the receptor subtype and/or on the substituent present in the N 6 position. However, in all cases, the presence in the 2 position of a chlorine atom favoured the interaction with the A_2A subtype. These results demonstrated that, although the synthesized compounds were found to be quite inactive at the human A_2B subtype, adenine is a useful template for further development of simplified adenosine receptor antagonists with distinct receptor selectivity profiles.