摘要
By using active principles of Chinese medicinal materials as lead compounds soquinoline derivatives have been designed and synthesized.Their chemical structures include bisbenzylisoquinoline,benzyl-isoquinoline and protoberberine.Their cardiovascular effects were studied involving α-adrenoceptor,adenosine A_1,A_2 and DPH-calcium channel radioreceptor assays.In addition,calmodulin inhibiting,calcium antagonistic potassium channel blocking and antiplatelet aggre- gation activities were also performed.It was found that compound VI_(19) was a new potassium channe blocker with α-adrenoceptor antagonism,compound V_9,and V_(21) lowered blood pressure on various animal models with negative chronotropic action,compound VI_(13)possessed antiarrhythmic and antifi- brillation action,and it may be a candidate tot clinic evaluation.The structure-activity relationships deduced may provide a theoretical basis for further development of new agents.
本文报道了以中草药有效成分为先导物,设计合成了111个异喹啉衍生物包括双苄基异喹啉、苄基异喹啉、原小檗碱等类型化合物,对所合成衍生物进行α-受体,腺苷A1,A2,DHP钙通道放射受体分析以及其它的心血管活性研究,发现化合物VI_(19)具有α_1-受体拮抗作用新的钾通道阻滞剂,V_9和 V_(21)可降低多种动物模型的血压,而无反射性加速心律的副作用,VI_(13)具有抗心律失常和抗室颤作用,该化合物有可能进入临床试验。本文总结了部分化合物的构效关系为进一步研究新化合物提供理论基础。
