取代苄基异喹啉化合物与α-受体的亲和力及构效关系

Affinity to α-Adrenoceptor and QSAR of Some Substituted Benzylisoquinoline

由于粉防己碱裂解产物具有α-受体拮抗活性。结合钙拮抗剂某些结构特征,设计合成了一系列取代的苄基异喹啉衍生物,药理试验表明所合成化合物对α-受体具有不同程度的亲和力。为探索构效关系测定了所合成化合物HPLC保留因子(logK'),以此作为疏水参数结合其它的结构参数与α_1-受体亲和力进行Hansch分析,结果表明活性与取代基的疏水值π,共轭效应R正相关,与摩尔折射度MR负相关。

On the basis of the findings of cleaved products of tetrandrine to possess α-adrenoceptor antagonistic activity and integration of some structural features of calcium antagonists, 41 benzylisoquinoline derivatives were designed and synthesized. Radioreceptor binding assay showed that these compounds exhibited varied degree of affinity to α-adrenoeeptor and some of them possessed calcium antagonistic activity as well. The HPLC retention factor (logK') of these 41 compounds were determined as hydrophobic porameter. Oetanol/water partition coefficient (logP) of some compounds were also determined by shake flask method. QSAR analysis showed that the α_1-adrenoceptor affinity of these compounds increased significantly with the enhancement of π (hydrophobic character of substituents) and R (resonance effect), but reduced with the increase of MR (Molar Refractivity).