2,5-二芳基-1,3-氧硫戊环化合物的合成及iNOS/PAF双重抑制活性的研究  

Studies on the synthesis and iNOS/PAF dual inhibitory activities of 2,5-diaryl-1,3-oxothiolane compounds

作　　者：章国燕[1] 张奕华[1] 奚涛[2] 彭司勋[1] 

机构地区：[1]中国药科大学新药研究中心,江苏南京210009 [2]中国药科大学生物技术中心,江苏南京210009

出　　处：《中国药物化学杂志》2004年第2期84-90,共7页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金资助项目 (39770 86 9)

摘　　要：目的寻找既能抑制iNOS又能拮抗PAF受体的化合物。方法以具有PAF受体拮抗活性的 2 ,4 二芳基 1,3 二硫戊环为先导物 ,合成其生物电子等排体氧硫戊环化合物 ,并在其 2位芳环上引入具有iNOS抑制活性的基团 ,测定目标化合物的iNOS抑制活性和PAF受体拮抗活性。结果合成了 2 5个未见文献报道的目标物 ,其中 9个化合物 (Ⅰ2 ～Ⅰ7、Ⅰ10 、Ⅱ5、Ⅱ6)的iNOS抑制活性强于正在Ⅲ期临床的iNOS抑制剂氨基胍。PAF受体拮抗活性测试表明 ,Ⅰ4活性高于阳性对照药ZH 2 ,Ⅰ5活性与ZH 2相当 ,Ⅰ2 、Ⅰ6、Ⅰ8、Ⅰ10 和Ⅱ5、Ⅱ6活性稍低于ZH 2。结论Ⅰ4、Ⅰ5具有较高的iNOS/PAF双重抑制活性 ,值得进一步研究。Aim To search for iNOS/PAF dual inhibitors.Methods 2,4-diaryl-1,3-dithiolane was used as a leading compound and its bioisosteres,1,3-oxothiolane compounds were prepared.Some functionals with the iNOS inhibitory activities were introduced into the 2-aryl ring of the 2,5-diaryl-1,3-oxothiolane compounds,and the iNOS inhibitory activity and PAF antagonistic activity of these compounds obtained were biologically evaluated.Results Totally twenty-five target compounds were designed and synthesized.The assays of the iNOS inhibitory effects showed compounds Ⅰ 2～Ⅰ 7,Ⅰ 10 and Ⅱ 5 and Ⅱ 6 were more potent than the control aminoguanidine.The PAF antagonistic activities of the 9 target compounds were evaluated.Ⅰ 4 was more potent than the control ZH-2 and Ⅰ 5 was active and comparable to ZH-2.Ⅰ 2,Ⅰ 6,Ⅰ 8,Ⅰ 10 and Ⅱ 5 and Ⅱ 6 were somewhat less potent than ZH-2.Conclusion Compounds Ⅰ 4 and Ⅰ 5 have proved to be iNOS/PAF dual inhibitors,which are worthy of further study.

关 键 词：药物化学 制备 化学合成 2 5-二芳基-1 3-氧硫戊环 iNOS/PAF双重抑制剂 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]