FLUORONUCLEOSIDES AS CNS TARGETED ANTIHIV AGENTS

中枢神经系统（CNS）HIV感染可导致严重问题 例如艾滋病相关痴呆症。然而，大脑排除了许多活跃的 血脑屏障（BBB）的存在使抗HIV药物的使用受到限制。客观 该项目的主要内容是设计、合成和抗艾滋病毒评价 具有改善的CNS转运性质的前药。F-ddA，LMCH药物， NCI I期临床试验的最后阶段，被用作 原型前药在一个不断发展的数学模型，旨在选择 从一组16种新化合物中选出最佳CNS候选物 为此目的而合成的。这些化合物可以酶促地 由腺苷脱氨酶（ADA）水解为F-ddI，一种抗HIV活性 化合物.化合物性质（亲脂性、酸稳定性）决定 BBB渗透，CNS中ADA催化的水解产生 活性物质（F-ddI）。这些大鼠组织分布数据 化合物的产生是为了与化合物的性质相关联 在一个基于生理学的数学模型中。此外，更高效 2 '-氟苷的合成方法正在研究中， 新发现的化学 艾滋病标题：“氟尿嘧啶作为CNS靶向抗艾滋病药物”

Central nervous system (CNS) HIV infections can cause severe problems such as AIDS-related dementia. The brain, however, excludes many active anti-HIV drugs because of the blood brain-barrier (BBB). The objective of this project is the design, synthesis and anti-HIV evaluation of prodrugs with improved CNS transport properties. F-ddA, a LMCH drug in the final stages of a NCI Phase I clinical trial, is being used as a prototype prodrug in an evolving mathematical model designed to choose an optimum CNS candidate from among a group of 16 new compounds synthesized for that purpose. These compounds can be enzymatically hydrolyzed by adenosine deaminase (ADA) to F-ddI, an anti-HIV-active compound. Compound properties (lipophilicity, acid-stability) determine BBB penetration, with ADA-catalyzed hydrolysis in the CNS generating the active material (F-ddI). Rat tissue distribution data for these compounds are being generated for correlation with compound properties in a physiologic-based mathematical model. In addition, more efficient methods for 2'-fluoronucleoside synthesis are being investigated based on newly discovered chemistry. AIDS title:"Fluoronucleosides as CNS-Targeted Anti-Aids Drugs"