关于不同取代的d4T环状和非环状苄基前核苷酸的水解稳定性和抗病毒活性的研究。

Study of different substituted cyclic and acyclic benzylpronucleotides of d4T relative to their hydrolytic stability and antiviral activity.

作者信息

Muus U, De Clercq E, Balzarini J, Naesens L, Meier C

机构信息

Institute of Organic Chemistry, University of Hamburg, Hamburg, Germany.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2003 May-Aug;22(5-8):791-5. doi: 10.1081/ncn-120022636.

DOI:10.1081/ncn-120022636

PMID:14565280

Abstract

CycloSal-d4TMP and two different bis(benzyl) phosphate triesters of the antivirally active nucleoside analog d4T were studied with regard to their chemical hydrolysis behavior at pH 7.3, in CEM/0 cell extracts, and their anti-HIV activity. In contrast to triesters 2-4, bis-(o-AB)-d4TMP 1 was found to be chemically exquisitely stable. All compounds led to the formation of d4TMP in cell extracts and all triesters achieved the TK-bypass.

摘要

研究了环戊基水杨酸-d4TMP以及抗病毒活性核苷类似物d4T的两种不同的双（苄基）磷酸三酯在pH 7.3条件下于CEM/0细胞提取物中的化学水解行为及其抗HIV活性。与三酯2-4不同，双（邻-AB）-d4TMP 1在化学上表现出极高的稳定性。所有化合物在细胞提取物中均导致d4TMP的形成，并且所有三酯均实现了胸苷激酶（TK）旁路。