Daly J W, Padgett W, Thompson R D, Kusachi S, Bugni W J, Olsson R A
Biochem Pharmacol. 1986 Aug 1;35(15):2467-81. doi: 10.1016/0006-2952(86)90042-0.
A series of 145 N6-substituted adenosines have been screened as inhibitors of the binding of [3H]cyclohexyladenosine to an A1-adenosine receptor in rat brain membranes and the results compared to the potencies of these analogs in increasing coronary blood flow via activation of an A2-adenosine receptor. The A1 receptor shows greater stereoselectivity in the N6 region of the receptor towards asymmetric aralkyl substituents, and shows greater bulk tolerance in the N6 region of the receptor such that it retains affinity for certain N6-tertiary alkyladenosines and N6-cycloalkyladenosines that are inactive at the coronary A2 receptor. At the A1 receptor, the most potent analogs have either aliphatic N6-substituents with four or more methylene residues or have an N6-halophenyl substituent. At the A2 receptor, the most potent analogs have an N6-phenethyl or similar heteroarylethyl substituent. Certain sets or series of analogs appear useful for identifying the subtypes of adenosine receptors involved in physiological functions.
一系列145种N6-取代腺苷已被筛选作为[3H]环己基腺苷与大鼠脑膜中A1-腺苷受体结合的抑制剂，并将结果与这些类似物通过激活A2-腺苷受体增加冠状动脉血流量的效力进行比较。A1受体在受体的N6区域对不对称芳烷基取代基表现出更大的立体选择性，并且在受体的N6区域表现出更大的体积耐受性，以至于它对某些在冠状动脉A2受体上无活性的N6-叔烷基腺苷和N6-环烷基腺苷保持亲和力。在A1受体处，最有效的类似物具有带有四个或更多亚甲基残基的脂肪族N6-取代基或具有N6-卤代苯基取代基。在A2受体处，最有效的类似物具有N6-苯乙基或类似的杂芳基乙基取代基。某些组或系列的类似物似乎有助于鉴定参与生理功能的腺苷受体亚型。
