腺苷A2B受体上腺苷类似物的功能筛选：寻找强效激动剂。
A functional screening of adenosine analogues at the adenosine A2B receptor: a search for potent agonists.
作者信息
de Zwart M, Link R, von Frijtag Drabbe Künzel J K, Cristalli G, Jacobson K A, Townsend-Nicholson A, IJzerman A P
机构信息
Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
出版信息
Nucleosides Nucleotides. 1998 Jun;17(6):969-85. doi: 10.1080/07328319808004215.
Abstract
Various adenosine analogues were tested at the adenosine A2B receptor. Agonist potencies were determined by measuring the cyclic AMP production in Chinese Hamster Ovary cells expressing human A2B receptors. 5'-N-Substituted carboxamidoadenosines were most potent. 5'-N-Ethylcarboxamidoadenosine (NECA) was most active with an EC50 value of 3.1 microM. Other ribose modified derivatives displayed low to negligible activity. Potency was reduced by substitution on the exocyclic amino function (N6) of the purine ring system. The most active N6-substituted derivative N6-methyl-NECA was 5 fold less potent than NECA. C8- and most C2-substituted analogues were virtually inactive. 1-Deaza-analogues had a reduced potency, 3- and 7-deazaanalogues were not active.
摘要
在腺苷A2B受体上测试了多种腺苷类似物。通过测量表达人A2B受体的中国仓鼠卵巢细胞中的环磷酸腺苷生成来确定激动剂效力。5'-N-取代的羧酰胺基腺苷效力最强。5'-N-乙基羧酰胺基腺苷（NECA）活性最高，EC50值为3.1微摩尔。其他核糖修饰的衍生物活性低至可忽略不计。嘌呤环系统的环外氨基功能（N6）上的取代会降低效力。活性最高的N6-取代衍生物N6-甲基-NECA的效力比NECA低5倍。C8-和大多数C2-取代的类似物实际上没有活性。1-脱氮类似物效力降低，3-和7-脱氮类似物没有活性。
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