Henkel J G, Sikand N, Makriyannis A, Gianutsos G
J Med Chem. 1981 Oct;24(10):1258-60. doi: 10.1021/jm00142a026.
In order to assess the potential for sympathomimetic or sympatholytic activity within the series of catecholamine beta-sulfonates 3a-c, alpha- and beta-adrenoceptor binding affinities were determined using rat brain homogenate preparations. Furthermore, their potential for indirect activity was assessed by measurement of blockade of norepinephrine uptake into rat synaptosomal preparations. Activity was uniformly low or nonexistent throughout the series. The possibility of unfavorable solution conformational distribution within the series was investigated by examination of the side chain vicinal 1H NMR coupling constants, but no differences that could account for the lack of affinity were found. The observed behavior may be due to receptor intolerance of the bulky beta-sulfonate substituent or an electronic mismatch in which normal H bonding is significantly altered.
为了评估儿茶酚胺β-磺酸盐3a - c系列化合物内拟交感或抗交感活性的潜力，使用大鼠脑匀浆制剂测定了α和β肾上腺素能受体结合亲和力。此外，通过测量大鼠突触体制剂中去甲肾上腺素摄取的阻断情况来评估它们的间接活性潜力。整个系列的活性均一致较低或不存在。通过检查侧链邻位1H NMR耦合常数研究了该系列化合物内不利溶液构象分布的可能性，但未发现可解释亲和力缺乏的差异。观察到的行为可能是由于庞大的β-磺酸盐取代基导致受体耐受性差，或者是由于正常氢键显著改变的电子不匹配。
