Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Pusztaszeri út 59, H-1025 Budapest, Hungary.
Bioorg Med Chem. 2013 Jul 1;21(13):3760-79. doi: 10.1016/j.bmc.2013.04.034. Epub 2013 Apr 23.
Novel N-hydroxyalkyl-2-aminophenothiazines implying a tetrazole moiety at the alkyl chain have been synthesized by hydroboration-oxidation of dienes followed by Buchwald-Hartwig cross-coupling reaction. Also, some sulfoxide and sulfone derivatives have been prepared by selective oxidations. MDR inhibition studies on rat hepatocyte cell culture revealed that some derivatives exhibit marked biological efficacy exceeding that of the standard verapamil (e.g., 3h, 4h, 16). Selected derivatives were subjected to chemical resolution to provide both enantiomers which were shown of similar activity on P-gp interaction measurements. The new compounds exhibited no toxicity.
新型 N-羟烷基-2-氨基吩噻嗪衍生物在碳链上引入了四唑基团，通过双烯的硼氢化-氧化反应，然后进行 Buchwald-Hartwig 交叉偶联反应合成。此外，还通过选择性氧化制备了一些亚砜和砜衍生物。在大鼠肝细胞培养物的 MDR 抑制研究中，发现一些衍生物表现出明显的生物学功效，超过了标准维拉帕米（例如 3h、4h、16）。选择的衍生物进行化学拆分，提供了两种对映体，它们在 P-糖蛋白相互作用测量中表现出相似的活性。新化合物没有毒性。
