L B Townsend, K S Gudmundsson, S M Daluge, J J Chen, Z Zhu, G W Koszalka, L Boyd, S D Chamberlain, G A Freeman, K K Biron, J C Drach
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引用次数: 17
Abstract
The potent activity of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) against Human Cytomegalovirus with the concomitant low cellular toxicity at concentrations that inhibit viral growth prompted considerable interest in this research area. This interest was moderated by the pharmacokinetic studies of TCRB in rats and monkeys that revealed the instability of TCRB in vivo. These studies suggested that the instability was due to a cleavage of the glycosidic bond in vivo which released the heterocycle (2,5,6-trichlorobenzimidazole) into the bloodstream. This prompted us to initiate synthetic studies designed to increase the stability of the glycosidic bond of TCRB and BDCRB. Several synthetic approaches to address this and other problems are presented.
2,5,6-三氯-1-(β - d -核呋喃基)苯并咪唑(TCRB)对人巨细胞病毒的有效活性，以及在抑制病毒生长的浓度下伴随的低细胞毒性，引起了人们对这一研究领域的极大兴趣。这种兴趣被TCRB在大鼠和猴子身上的药代动力学研究所缓和，这些研究揭示了TCRB在体内的不稳定性。这些研究表明，这种不稳定性是由于体内糖苷键的断裂释放了杂环(2,5,6-三氯苯并咪唑)进入血液。这促使我们开始了旨在提高TCRB和BDCRB糖苷键稳定性的合成研究。提出了几种综合方法来解决这个问题和其他问题。
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