N,N'-二卤代苯基-4-甲氧基-1,3-苯二磺酰胺类化合物的设计、合成及体外抗血小板聚集活性评价  

Design, synthesis of novel N, N'-bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides and evaluation of their anti-platelet aggregation activity

作　　者：李贵良[1] 王潇[2] 孟侠[1] 林永彬 李旭[1] 刘秀杰[1] 

机构地区：[1]天津理工大学化学化工学院,天津300384 [2]哈尔滨工业大学应用化学系,黑龙江哈尔滨150001

出　　处：《药学学报》2015年第2期185-190,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金主任基金研究项目(21342014)

摘　　要：依据药物化学结构设计中拼合和等排原则,拼合抗血小板聚集药物吡考他胺(picotamide)和利曲他班(linotroban)的结构,用磺酰基代替甲酰基,设计合成了N,N'-二卤代苯基-4-甲氧基-1,3-苯二磺酰胺系列化合物(4a^4m、5a^5n),各化合物的结构由IR、1H NMR和HR-MS光谱确证。以吡考他胺为阳性对照药,采用Born比浊法检测目标化合物抗二磷酸腺苷(ADP)诱导的体外抗血小板聚集活性,结果显示其中12个化合物(4b、4f、4l、5b、5d^5g、5j、5k、5m和5n)对ADP诱导的血小板聚集的抑制活性优于阳性对照药吡考他胺。此外,初步探讨了目标化合物的构效关系。Combining the structural features of picotamide and linotroban, a series of N, N ＇-bis-（halogenophenyl）-4-methoxybenzene-1, 3-disulfonamides were designed and synthesized on the basic principles of drug design. The structures of target compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet aggregation activity was evaluated by Born turbidimetric method with adenosine diphosphate（ADP） as the platelet aggregation inducers. The assay results showed that twelve compounds（4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n） were found to have superior anti-platelet aggregation activities than the positive drug picotamide. The preliminary structure-activity relationship（SAR） has been explored.

关 键 词：合成 4-甲氧基-1 3-苯二磺酰胺 吡考他胺 利曲他班 抗血小板聚集 

分 类 号：R916[医药卫生—药学]