FLUORONUCLEOSIDES AS CNS TARGETED ANTIHIV AGENTS

中枢神经系统(CNS)艾滋病毒感染可导致严重问题 例如与艾滋病相关的痴呆症。然而，大脑排除了许多活跃的 抗HIV药物因为血脑屏障(BBB)。目标是 该项目的主要内容是设计、合成和抗艾滋病毒评价。 具有改善的中枢神经系统转运特性的前药。F-Dda，一种LMCH药物 NCI I期临床试验的最后阶段正被用作 进化数学模型中的原型前药，旨在选择 从16个新化合物中选出最佳的CNS候选化合物 为此目的而合成的。这些化合物可以在酶的作用下 被腺苷脱氨酶(ADA)水解为抗HIV活性的F-DDI 化合物。化合物的性质(亲油性、酸稳定性)决定 血脑屏障穿透，与ADA催化的中枢神经系统的水解产生 活性物质(F-DDI)。这些物质的大鼠组织分布数据 生成化合物是为了与化合物性质相关联 在一个基于生理的数学模型中。此外，更高效 合成2‘-氟核苷的方法正在研究中。 关于新发现的化学。 艾滋病题：《作为中枢神经系统靶向抗艾滋病药物的氟核苷》

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"