New, non-adenosine, high-potency agonists for the human adenosine A2B receptor with an improved selectivity profile compared to the reference agonist n-ethylcarboxamidoadenosine

被引：140

作者：

Beukers, MW ^{[1
]}

Chang, LCW ^{[1
]}

Künzel, JKVD ^{[1
]}

Mulder-Krieger, T ^{[1
]}

Spanjersberg, RF ^{[1
]}

Brussee, J ^{[1
]}

Ijzerman, AP ^{[1
]}

机构：

[1] Gorlaeus Labs, LACDR, Div Med Chem, NL-2300 RA Leiden, Netherlands

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 15期

关键词：

D O I：

10.1021/jm049947s

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The adenosine A(2B) receptor is the least well characterized of the four known adenosine receptor subtypes because of the absence of potent, selective agonists. Here, we present five non-adenosine agonists. Among them, 2-amino-4-(4-hydroxyphenyl)-6-(1H-imidazol-2-ylmethylsulfanyl)pyridine-3,5.-dicarbonitrile, 17, LUF5834, is a high-efficacy partial agonist with EC50 = 12 nM and 45-fold selectivity over the adenosine A(3) receptor but lacking selectivity versus the A, and A(2A) subtypes. Compound 18, LUF5835, the 3-hydroxyphenyl analogue, is a full agonist with EC50 = 10 nM.

引用

页码：3707 / 3709

页数：3

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