Lin A J, Lee M, Klayman D L
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
J Med Chem. 1989 Jun;32(6):1249-52. doi: 10.1021/jm00126a017.
A new series of hydrolytically stable and water-soluble dihydroartemisinin derivatives with optically active side chains was prepared as potential antimalarial agents. This was an effort to prepare compounds with activity superior to that of artelinic acid and to examine the impact of the stereospecificity of the introduced alkyl side chain on biological properties. The ester derivatives (6a-d) possess superior in vitro activity to artemisinin, artemether, and arteether against two strains of Plasmodium falciparum (D-6 and W-2); however, conversion of the esters to their corresponding acids drastically reduces their antimalarial activity. None of the new acids possess in vitro antimalarial activity superior to that of artelinic acid. Although there appears to be limited stereospecificity for antimalarial activity among the acids (7a-d) tested, significant differences in antimalarial activity was seen among the esters.
制备了一系列具有光学活性侧链的新型水解稳定且水溶性的双氢青蒿素衍生物作为潜在的抗疟剂。这是为了制备活性优于青蒿琥酯的化合物，并研究引入的烷基侧链的立体特异性对生物学性质的影响。酯衍生物（6a-d）对两株恶性疟原虫（D-6和W-2）具有优于青蒿素、蒿甲醚和蒿乙醚的体外活性；然而，酯转化为相应的酸会大幅降低其抗疟活性。新的酸均不具有优于青蒿琥酯的体外抗疟活性。尽管在所测试的酸（7a-d）中抗疟活性的立体特异性似乎有限，但酯之间的抗疟活性存在显著差异。
