摘要
目的 寻找克鲁斯氏锥体虫体半胱氨酸蛋白酶Cruzain的小分子抑制剂。方法 根据对Cruzain分子结构的计算机模拟设计结果 ,选用N ,N 双取代脲为先导结构 ,目标化合物的合成采用Curtius重排反应 ,测定了化合物的体外抑制Cruzain的IC50 值。结果 设计并合成了 2 1个未见文献报道的双取代脲衍生物 ,确证了它们的化学结构。结论 生物活性测定结果显示 ,所合成的化合物均有不同程度的抑制Cruzain的活性 ,其中化合物IV9和IV17的活性好于对照药tf 175。IV8的活性与对照药tf
OBJECTIVE To search the small molecular inhibitors of cysteine protease of Tryponosoma cruzi.METHOD The N,N-bis-substituted urea was chosen as the lead scaffold based on the computational molecular modeling of cruzain. The target compounds were synthesized through the Curtius rearrangement, The IC_(50) values of the compounds against cruzain in vitro have also been determined.RESULTS Total 21 new compounds that had never been reported were designed and synthesized, the structures of synthesized compounds were confirmed by ()~1H-NMR spectroscopy and HRMS(EI).CONCLUSION All synthesized compounds exhibited certain activities against cruzain in vitro, in which the compound IV_9 and IV_(17) exhibited better activity than the control drug, tf-175. The IC_(50) value of compound IV_8 was as same as that of tf-175.
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2004年第5期361-365,共5页
Chinese Journal of Modern Applied Pharmacy
