腺苷酸受体:选择性受体激动剂和拮抗剂的发展。
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戴利JW,雅各布森KA, Ukena D
腺苷酸受体:选择性受体激动剂和拮抗剂的发展。
尖端生物研究1987;230:41 - 63。
- PubMed ID
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3588607 (在PubMed]
- 文摘
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腺苷调节各种生理功能通过与A1和A2腺苷酸受体,受体激动剂调节抑制和刺激,腺苷酸环化酶的分别。在心血管系统、A2受体调节血管舒张和降低血压,而A1受体调节心脏萧条。腺苷酸环化酶的参与在这些反应仍未得到解决。腺苷类似物特别是N6-substituted化合物在A1受体比A2受体更有效。腺苷受体的次区域与N6-substituent交互A1和A2受体不同,特别是对苯交互,宽容和立体选择性。合成了一系列para-substituted N6-phenyladenosines基于“功能化同类”的方法,化学活性基团,如胺和羧酸,介绍的终点站链。从“功能化同类”合成各种配合每个包含一个常见的药效团。特定的腺苷A1受体轭合物是高度选择性。黄嘌呤是古典为腺苷酸受体拮抗剂对他们的许多药理的行为可能是由于腺苷酸受体的封锁。咖啡因和茶碱是A2和A2受体几乎无选择性。 Replacement of the methyl groups of theophylline with n-propyl or larger alkyl groups yields xanthines with selectivity for A1 receptors, particularly when combined with an 8-phenyl moiety. Most 1,3-dialkyl-8-phenyl xanthines are very insoluble, but incorporation of polar aryl substituents, such as sulfo or carboxy to increase solubility, results in marked reduction in potency and selectivity. A new series of more hydrophilic 1,3-dipropyl-8-phenylxanthines has been synthesized using the "functionalized congener" approach. Certain conjugates of 8-[4-(carboxymethyloxy)phenyl 1]1,3-dipropylxanthine display A1 selectivity in biochemical and cardiovascular models. Certain analogs of caffeine in which the methyl group at the 1- or 7-position is replaced with a propargyl or propyl group display selectivity for A2 receptors. The profile of a series of adenosine analogs or of xanthine antagonists can be used to define the nature of adenosine receptors.