作用于配体门控氯离子通道3-羟基异噁(噻)唑衍生物的研究进展  

Advances in 3-Hydroxyisoxazole(3-Hydroxyisothiazole)Analogues Acting on Ligand-Gated Chloride Channels

作　　者：肖胜 王倩 钟慧勉 巨修练[1] 刘根炎 XIAO Sheng;WANG qian;ZHONG Huimian;JU Xiulian;LIU Genyan(School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430205,China)

机构地区：[1]武汉工程大学化工与制药学院,湖北武汉430205

出　　处：《武汉工程大学学报》2020年第4期360-365,共6页Journal of Wuhan Institute of Technology

基　　金：国家自然科学基金(21807082);国家级大学生创新创业训练计划(201910490003);湖北省自然科学基金(2017CFB121);湖北省教育厅科学技术研究项目(Q20171503)。

摘　　要：3-羟基异噁(噻)唑衍生物是一类重要的五元杂环化合物,具有丰富的药理和生理活性,在医药、农药、化工等领域有广泛的应用。部分3-羟基异噁(噻)唑化合物对γ-氨基丁酸和谷氨酸门控氯离子通道受体有显著的激动或拮抗作用。综述了三类典型的3-羟基异噁(噻)唑衍生物:蝇蕈醇类,5-(4-哌啶基)-3-羟基异噁唑类和鹅膏氨酸类,介绍了这三类化合物作为γ-氨基丁酸和谷氨酸受体激动剂或拮抗剂的应用,并对这些化合物的进一步分子设计进行了展望。对异噁(噻)唑环进行结构修饰是设计配体门控氯离子通道激动剂或拮抗剂的关键,在环上引入不同取代基或构造双环可能导致3-羟基异噁(噻)唑衍生物的药理活性发生显著变化,有助于发现药物或农药的苗头化合物。3-Hydroxyl isoxazoles(or isothiazoles) are an important class of five-membered heterocyclic compounds with pharmacological and physiological activities,and have been widely applied in the fields of medicine,pesticide,and chemical engineering. 3-Hydroxyl isoxazoles(or isothiazoles) have significant agonism or antagonism effect on γ-aminobutyric acid-and glutamate-gated chloride ion channels. We reviewed three representative types of 3-hydroxyl isoxazoles(or isothiazoles):muscimols,5-(4-piperidyl)-3-isoxazolols and ibotenic acids,and described their applications as agonist or antagonist leads of γ-aminobutyric acid and glutamate receptors,and prospected their further molecular design. The key strategy for designing the agonists or antagonists of ligand-gated chloride ion channels is to modify the isothiazole or isoxazole ring. The introduction of different substituents on the ring or the construction of a bicyclic ring might lead to great changes in the pharmacological activity of these 3-hydroxyl isoxazoles(or isothiazoles),which could be helpful in finding hit compounds of drugs or pesticides.

关 键 词：3-羟基异噁唑 3-羟基异噻唑 Γ-氨基丁酸受体 谷氨酸受体 

分 类 号：O626[理学—有机化学]