Non-xanthine heterocycles: activity as antagonists of A1- and A2-adenosine receptors.
Non-xanthine heterocycles: activity as antagonists of A1- and A2-adenosine receptors.
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非黄嘌呤杂环化合物：作为 A1- 和 A2- 腺苷受体拮抗剂的活性。
DOI：
10.1016/0006-2952(88)90139-6
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发表时间：
1988
影响因子：
5.8
通讯作者：
Ukena,D
中科院分区：
文献类型：
--
作者：
Daly,JW;Hong,O;Padgett,WL;Shamim,MT;Jacobson,KA;Ukena,D
在人血小板和大鼠嗜铬细胞瘤细胞膜上发现了多种非黄嘌呤杂环化合物，它们可拮抗[~ 3 H]苯基异丙基腺苷与大鼠脑A_1-腺苷受体的结合，并通过N-乙基羧酰胺腺苷与A_2-腺苷受体的相互作用激活腺苷酸环化酶。在A1和A2-腺苷受体上，吡唑并吡啶类药物曲唑酯、卡他唑酯和依他唑酯比茶碱强几倍。然而，吡唑并吡啶的效力仍然比8-苯基茶碱和其它8-苯基-1，3-二烷基黄嘌呤低许多倍。结构相关的N6-取代的9-甲基腺嘌呤也是一种有效的腺苷拮抗剂，对A1受体具有选择性。没有几个芳基取代的杂环，包括噻唑并嘧啶，咪唑并吡啶，苯并咪唑，吡唑并喹啉，介离子黄嘌呤类似物和三唑并哒嗪表现出典型的8-苯基-1，3-二烷基黄嘌呤的高效力。呋喃基取代的三唑并喹唑啉对A1和A2受体都非常有效。一个蝶啶-2，4-二酮，1，3-dipropyllumazine，在A1-和A2-腺苷受体的效力略低于茶碱，而1，3-dimethyllumazine的效力要低得多。苯并喋啶-2，4-二酮，咯嗪，比茶碱更有效。其他具有拮抗活性的杂环化合物为二苯并氮杂卓、卡马西平和β-咔啉-3-羧酸乙酯。苯基咪唑啉可乐定没有活性，而相关的二羟苯基咪唑啉是一个弱的非竞争性腺苷拮抗剂。
A variety of non-xanthine heterocycles were found to be antagonists of binding of [3H]phenylisopropyladenosine to rat brain A1-adenosine receptors and of activation of adenylate cyclase via interaction ofN-ethylcarboxamidoadenosine with A2-adenosine receptors in human platelet and rat pheochromocytoma cell membranes. The pyrazolopyridines tracazolate, cartazolate and etazolate were several fold more potent than theophylline at both A1and A2-adenosine receptors. The pyrazolopyridines, however, were still many fold less potent than 8-phenyltheophylline and other 8-phenyl-1,3-dialkylxanthines. A structurally relatedN6-substituted 9-methyladenine was also a potent adenosine antagonist with selectivity for A1receptors. None of several aryl-substituted heterocycles, including a thiazolopyrimidine, imidazopyridines, benzimidazoles, a pyrazoloquinoline, a mesoionic xanthine analog and a triazolopyridazine exhibited the high potency typical of 8-phenyl-1,3-dialkylxanthines. A furyl-substituted triazoloquinazoline was very potent at both A1and A2receptors. A pteridin-2,4-dione, 1,3-dipropyllumazine, was somewhat less potent than theophylline at A1- and A2-adenosine receptors, whereas 1,3-dimethyllumazine was much less potent. A benzopteridin-2,4-dione, alloxazine, was somewhat more potent than theophylline. Other heterocycles with antagonist activity were the dibenzazepine carbamazepine and β-carboline-3-ethyl carboxylate. The phenylimidazoline clonidine had no activity, whereas a related dihydroxyphenylimidazoline was a weak non-competitive adenosine antagonist.