4-甲(乙)氧基-1,3-苯二甲酰胺类化合物的合成及其体外抗血小板聚集活性

Synthesis and in vitro antiplatelet aggregation activities of 4-methoxy( ethoxy)-1,3-isophthalamide derivatives

目的本文参照前期吡考他胺衍生物的构效关系,设计制得10个4-乙氧基-1,3-苯二甲酰胺类化合物(系列2);为了评价和比较其体外抗血小板聚集活性,同时进行了相应10个4-甲氧基-1,3-苯二甲酰胺类化合物(系列1)的合成,以期寻找新的抗血栓药物。方法以2,4-二甲基苯酚为起始原料,经Willianmson反应、氧化、氯代和胺解反应共制得10个未见文献报道的目标化合物(系列2),各化合物结构均经1H-NMR、IR和MS确证。采用Born比浊法对20个目标化合物进行了体外抗血小板聚集活性初筛。结果与结论在新制得的10个4-乙氧基系列化合物中,2b的活性最高,2a、2b、2d、2f的活性优于阳性对照药物吡考他胺。结果表明,新制得的4-乙氧基系列化合物与系列1各化合物相比,在抗血小板聚集方面同样具有研究价值。

Picotamide was synthesized as an anti-platelet aggregation drug in 1987. Its ability to inhibit both TXA2 platelet synthase and platelet TXA2 receptors attracted the attention of researchers. To obtain new anti- platelet drugs ,20 target compounds were designed and synthesized, including 10 unreported compounds of 4- ethoxyisophthalamides（ series 2）. The structures of target compounds were identified by MS, 1H-NMR and IR. In vitro anti-platelet aggregation activities assessed by using Born test. The results revealed that six deri- vatives（2a,2b, 2d, 2f, 2i, 2j ）showed high platelet aggregation inhibitory activities in ten 4-ethoxyisoph- thalamides. The frist four compounds have superior anti-platelet aggregation activities than the reference drug picotamide and 2b was the best. These consequences suggested that this novel series has potential as struc- tural templates for the design of new platelet antiaggregatory drugs as the same as series 1 at least.