黄嘌呤衍生物的设计、合成及抗血小板聚集与神经保护活性研究  

Design,Synthesis and Anti-platelet Aggregation and Neuroprotection Activities Study of Xanthine Derivatives

作　　者：崔恩静 王宏伟 李家明 金凡 CUI En-jing;WANG Hong-wei;LI Jia-ming;JIN Fan(College of Pharmacy,Anhui University of Chinese Medicine,Hefei 230038,China;Department of Medicinal Chemistry,Anhui Academy of Chinese Medicine,Hefei 230012,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230038 [2]安徽省中医药科学院药物化学研究所,安徽合肥230012

出　　处：《化学试剂》2023年第8期57-64,共8页Chemical Reagents

基　　金：安徽省重大科技专项基金项目(15czz01077)。

摘　　要：为发现具有抗血小板聚集与神经保护作用的缺血性脑卒中候选药物,以可可碱、茶碱为原料,经取代、醚化、水解以及酸化反应,得到14个新型黄嘌呤芳酸类衍生物,并通过1HNMR、^(13)CNMR和ESI-MS对其进行结构确证。采用Bron比浊法测定目标化合物抗血小板聚集活性;进一步使用氧糖剥夺/复氧(Oxygen-glucose deprivation/reperfusion,OGD/R)诱导的大鼠大脑皮层神经元损伤模型对优选化合物进行神经保护活性测试。4-(3-(1,3-二甲基-2,6-二氧代-1,2,3,6-四氢-7H-嘌呤-7-基)丙氧基)3-甲氧基苯甲酸对花生四烯酸(Arachidonic acid,AA)和二磷酸腺苷(Adenosine diphosphate,ADP)诱导的血小板聚集均具有显著的抑制活性。4-(3-(1,3-二甲基-2,6-二氧代-1,2,3,6-四氢-7H-嘌呤-7-基)丙氧基)苯甲酸表现出与丁苯酞无显著性差异的神经保护活性。To develop ischemic stroke candidates with antiplatelet aggregation and neuroprotection,14 novel xanthine derivatives were obtained by substitution,etherification,hydrolysis and acidification reaction with theobromine and theophylline as starting materials,which were confirmed by 1HNMR,^(13)CNMR and ESI-MS.The antiplatelet aggregation activity of the target compounds were measured by Bron turbidimetry and further tested for neuroprotective activity against oxygen and glucose deprivation/reperfusion(OGD/R)-induced neurotoxicity in rat cortical neurons.4-(3-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7 H-purin-7-yl)propoxy)-3-methoxybenzoic acid had significant inhibitory activity on platelet aggregation induced by arachidonic acid(AA)and adenosine diphoshate(ADP).4-(3-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7 H-purin-7-yl)propoxy)benzoic acid presented no significant difference in neuroprotective activity compared with n-butylphthalide(NBP).

关 键 词：黄嘌呤衍生物 缺血性脑卒中 抗血小板聚集 神经保护 合成 

分 类 号：R914.5[医药卫生—药物化学]