摘要
目的 :寻找抑制诱生型一氧化氮合酶 ( i NOS)和血小板活化因子 ( PAF)并能在治疗败血性休克方面优于现有药物的化合物。方法 :以 PAF受体拮抗剂 2 ,4 -二芳基 -1 ,3-二硫戊环化合物为先导物 ,在其结构中引入有抑制 i NOS活性的异硫脲基并测定目标化合物的 i NOS抑制活性。结果和结论 :合成了二硫戊环异硫脲类化合物 ( ZW1～ 2 4) ,其结构均经 MS、1 HNMR、IR及元素分析鉴定。初步药理试验表明一些化合物具有显著的 i NOS抑制活性 ,其中 ZW-6、ZW-9、ZW-1 9、ZW-2 3、ZW-2 4的活性与正在 期临床研究的对照药氨基胍相当 ,ZW-2 1的活性大于氨基胍。
Objective: To search for novel potent compounds with PAF receptor antagonistic and iNOS inhibitory activities for the treatment of septic shock. Method: Isothiourea functional groups were introduced into the structure of PAF receptor antagonists, the iNOS inhibitory activity of the target compounds were measured according to kit method. Results and Conclusion: Twenty four dithiolane isothiourea compounds (ZW1 24) were synthesized, and their structures were confirmed by IR, \+1HNMR, MS spectra and elementary analysis. The results of preliminary pharmacological test showed that ZW 6, ZW 9, ZW 19, ZW 23 and ZW 24 had comparable activity to the control aminoguanidine, while ZW 21 was more potent than aminoguanidine.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2001年第1期1-7,共7页
Journal of China Pharmaceutical University
基金
国家自然科学基金!资助项目 (No.39770 86 9)
