Tanaka Hiromichi, Haraguchi Kazuhiro, Kumamoto Hiroki, Baba Masanori, Cheng Yung-Chi
School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Antivir Chem Chemother. 2005;16(4):217-21. doi: 10.1177/095632020501600402.
A nucleoside analogue 4'-ethynylstavudine (4'-Ed4T) was recently synthesized during chemical studies directed towards the development of a new route to 4'-carbon-substituted nucleosides. This compound was found to be more anti-HIV-1 active than the parent compound stavudine (d4T) and much less toxic to various cells and also to mitochondrial DNA synthesis. It became apparent that 4'-Ed4T is a better substrate for human thymidine kinase than d4T, and very much more resistant to catabolism by thymidine phosphorylase. The study of 4'-Ed4T against various drug-resistant HIV-1 mutants has disclosed its unique activity profile.
一种核苷类似物4'-乙炔基司他夫定（4'-Ed4T）最近在旨在开发一条合成4'-碳取代核苷新路线的化学研究过程中被合成出来。发现该化合物比母体化合物司他夫定（d4T）具有更强的抗HIV-1活性，并且对各种细胞以及线粒体DNA合成的毒性要小得多。很明显，4'-Ed4T比d4T是人类胸苷激酶更好的底物，并且对胸苷磷酸化酶的分解代谢具有更强的抗性。对4'-Ed4T针对各种耐药HIV-1突变体的研究揭示了其独特的活性特征。
