昆虫神经活性物质章鱼胺受体激动剂的设计、合成及其构效关系研究

Study on the Design,Synthesis and Structure-Activity Relationship of Some Potent Agonists Acting on Insect Neuroactive Octopaminergic Receptors

以章鱼胺能系统为靶标,设计并合成了72个取代苄基亚胺基-2-(口恶)唑烷和取代苯胺基2-(口恶)唑啉化合物。测定了目标化合物对美州大蠊神经索腺苷酸环化酶的活化作用。结果发现配体取代基的变化可引起对章鱼胺受体活性的较大幅度改变。邻氯苄基亚胺基-4-苯基-2-(口恶)唑啉显示与 OA 受体的较高亲和力(V_(max)=33.39,Km=0.33μmol·L^(-1)。应用 Hansch-Fujita 方法、RSA、MFA、药效团分析和分子模型技术等计算机辅助设计方法对它们的结构活性关系进行剖析并建立了一些可信度高的模型。

With the biorational objective of designing octopaminergic insecticides,some new types of agonists such as substituted benzylamino-2-oxazolines and arylimino-2-oxazolidines were designed and synthesized.These novel compounds were tested the cAMP increasing level against adenylate-cyclase in the nerve cord of American cockroach,Periplaneta americana L. The results showed that the potential activity with the OA receptors differed a lot with the groups substituted at the phenyl moiety,o-Benzylamino-4-phenyl-2-oxazoline displayed high potency with OA receptors(V_(max)=33.39,Km=0.33μmol·L^(-1)).Furthermore,an exten- sive approach on the structure-activity relationship was performed by Hansch-Fujita 2D- QSAR,RSA,MFA,Pharmacophore analysis and Molecular Modeling techniques.Some models established in this study were proved to he useful and reliable.