Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Czech Republic.
Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branišovská 31, CZ-37005 České Budějovice, Czech Republic.
ACS Infect Dis. 2021 Apr 9;7(4):917-926. doi: 10.1021/acsinfecdis.1c00062. Epub 2021 Mar 26.
Human African Trypanosomiasis caused by species is one of the most damaging neglected tropical diseases. While the number of newly diagnosed cases per year is record low, there is still high interest in the development of new antitrypanosomal agents in case of resistance to currently used drugs and their combinations, and to replace drugs with serious side effects. We report a series of 7-methyl-7-deazapurine (5-methyl-pyrrolo[2,3-]pyrimidine) ribonucleosides bearing alkyl, methylsulfanyl, methylamino, or diverse alkoxy groups at position 6 that was prepared through glycosylation of 6-chloro-7-methyl-7-deazapurine followed by nucleophilic substitutions or cross-coupling reactions at position 6 and deprotection. Most of the title nucleosides displayed significant activity against and at submicromolar or nanomolar concentrations and low cytotoxicity and thus represent promising candidates for further development.
人类非洲锥虫病由 物种引起，是最具破坏性的被忽视热带病之一。虽然每年新诊断病例的数量创历史新低，但人们仍然对开发新的抗锥虫药物感兴趣，以防现有药物及其组合产生耐药性，以及用具有严重副作用的药物替代它们。我们报告了一系列在 6 位带有烷基、甲硫基、甲氨基或各种烷氧基的 7-甲基-7-脱氮嘌呤（5-甲基-吡咯并[2,3-]嘧啶）核苷，它们是通过 6-氯-7-甲基-7-脱氮嘌呤的糖苷化，然后在 6 位进行亲核取代或交叉偶联反应以及脱保护制备得到的。大多数标题核苷在亚微摩尔或纳摩尔浓度下对 和 表现出显著的活性，且细胞毒性低，因此是进一步开发的有希望的候选物。
