Jacobson K A, Kirk K L, Padgett W L, Daly J W
J Med Chem. 1985 Sep;28(9):1341-6. doi: 10.1021/jm00147a039.
A series of functionalized congeners of adenosine based on N6-phenyladenosine, a potent A1-adenosine receptor against, was synthesized. Derivatives of the various congeners should be useful as receptor and histochemical probes and for the preparation of radioligands and affinity columns or as targeted drugs. N6-[4-(Carboxymethyl)phenyl]adenosine served as the starting point for synthesis of the methyl ester, the methyl amide, the ethyl glycinate, and various substituted anilides. One of the latter, N6-[4-[[[4-(carbomethoxymethyl)anilino]carbonyl]methyl]phenyl] adenosine, served as the starting point for the synthesis of another series of congeners including the methyl amide, the hydrazide, and the aminoethyl amide. The terminal amino function of the last congener was acylated to provide further analogues. The various congeners were potent competitive antagonists of binding of N6-[3H]cyclohexyladenosine to A1-adenosine receptors in rat cerebral cortical membranes. The affinity of the congener for the A1 receptor was highly dependent on the nature of the spacer group and the terminal moiety with Ki values ranging 1-100 nM. A biotinylated analogue had a Ki value of 11 nM. A conjugate derived from the Bolton-Hunter reagent had a Ki value of 4.5 nM. The most potent congener contained a terminal [(aminoethyl)amino]carbonyl function and had a Ki value of less than 1 nM.
基于强效A1 - 腺苷受体拮抗剂N6 - 苯基腺苷，合成了一系列腺苷功能化类似物。各种类似物的衍生物可用作受体和组织化学探针，用于制备放射性配体和亲和柱，或用作靶向药物。N6 - [4 - （羧甲基）苯基]腺苷用作合成甲酯、甲酰胺、甘氨酸乙酯和各种取代酰苯胺的起始原料。后者之一，N6 - [4 - [[[4 - （甲氧基羰基甲基）苯胺基]羰基]甲基]苯基]腺苷，用作合成另一系列类似物的起始原料，包括甲酰胺、酰肼和氨乙基酰胺。最后一种类似物的末端氨基功能被酰化以提供更多类似物。各种类似物是N6 - [3H]环己基腺苷与大鼠大脑皮层膜中A1 - 腺苷受体结合的强效竞争性拮抗剂。类似物对A1受体的亲和力高度依赖于间隔基团和末端部分的性质，Ki值范围为1 - 100 nM。一种生物素化类似物的Ki值为11 nM。一种衍生自博尔顿 - 亨特试剂的缀合物的Ki值为4.5 nM。最有效的类似物含有末端[（氨乙基）氨基]羰基功能，Ki值小于1 nM。
