抗艾滋病药物。第62部分：2'-取代的4-甲基-3',4'-二-O-（-）-樟脑酰基-（+）-顺式凯拉内酯（4-甲基DCK）类似物的抗HIV活性。
Anti-AIDS agents. Part 62: anti-HIV activity of 2'-substituted 4-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs.
作者信息
Zhang Qian, Chen Ying, Xia Peng, Xia Yi, Yang Zheng-Yu, Yu Donglei, Morris-Natschke Susan L, Lee Kuo-Hsiung
机构信息
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 200032, China.
出版信息
Bioorg Med Chem Lett. 2004 Dec 6;14(23):5855-7. doi: 10.1016/j.bmcl.2004.09.032.
Four 4-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs (7a-d) with different alkyl substituents at the 2'-position were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 2'-Methyl-2'-ethyl-4-methyl DCK (7b) was more potent (EC(50)=0.22 microM, TI>175) than the other three compounds (7a, 7c, and 7d), but significantly less potent than 4-methyl DCK (2, EC(50)=0.0059 microM, TI>6600). The bioassay results indicated that the 2'-substituents had a strong effect on the anti-HIV activity, and gem-dimethyl substitution at the 2'-position was greatly preferable to larger alkyl substituents or hydrogen atoms.
合成了4个在2'-位具有不同烷基取代基的4-甲基-3',4'-二-O-(-)-樟脑酰基-(+)-顺式凯刺内酯（4-甲基DCK）类似物（7a-d），并评估了它们对H9淋巴细胞中HIV-1复制的抑制作用。2'-甲基-2'-乙基-4-甲基DCK（7b）比其他三种化合物（7a、7c和7d）更具活性（EC(50)=0.22微摩尔，治疗指数>175），但活性明显低于4-甲基DCK（2，EC(50)=0.0059微摩尔，治疗指数>6600）。生物测定结果表明，2'-位取代基对抗HIV活性有强烈影响，2'-位的偕二甲基取代比更大的烷基取代基或氢原子更具优势。
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