Olsson R A, Khouri E M, Bedynek J L, McLean J
Circ Res. 1979 Oct;45(4):468-78. doi: 10.1161/01.res.45.4.468.
Intracoronary adenosine infusions in conscious dogs produced half-maximal coronary vasodilation at 0.57 +/- 0.18 (SD) microns and at 1.01 +/- 0.25 microns in open-chest dogs. In both preparations, adenosine at concentrations in the range found in cardiac muscle by direct analysis produced coronary vasodilation equal to that attained during a maximum reactive hyperemic response. The quantitative structure-activity relationship technique was applied to data on the coronary vasoactivity of 68 adenosine analogs to identify the chemical features of this molecule that determine its vasoactivity. These are: (1) the size of the purine base; (2) the inductive effect of C-2 substituent; (3) the electron-withdrawing effect of the C-6 substituent; (4) the glycosylic torsion angle; (5) the ability of the C-2' and C-3' hydroxyls to participate in hydrogen bonding; (7) the absence of sterically hindering groups in the vicinity of C-2' and, more importantly, C-3'; and (8) the inductive effect of the C-5' substituent. The hydrophobicity of these analogs did not correlate with vasoactivity, suggesting that the hydrophilicity of the ribose moiety overshadows any hydrophobic influence of the very weakly aromatic purine base.
在清醒犬体内进行冠状动脉内腺苷输注时，产生最大冠状动脉扩张作用一半时的腺苷浓度，在清醒犬为0.57±0.18（标准差）微米，在开胸犬为1.01±0.25微米。在这两种制备方法中，通过直接分析在心肌中发现的浓度范围内的腺苷所产生的冠状动脉扩张，与最大反应性充血反应期间所达到的扩张程度相同。将定量构效关系技术应用于68种腺苷类似物的冠状动脉血管活性数据，以确定该分子决定其血管活性的化学特征。这些特征包括：（1）嘌呤碱基的大小；（2）C-2取代基的诱导效应；（3）C-6取代基的吸电子效应；（4）糖苷扭转角；（5）C-2'和C-3'羟基参与氢键形成的能力；（7）C-2'附近，更重要的是C-3'附近不存在空间位阻基团；（8）C-5'取代基的诱导效应。这些类似物的疏水性与血管活性不相关，这表明核糖部分的亲水性掩盖了非常弱的芳香嘌呤碱基的任何疏水影响。
