DIDEOXYNUCLEOSIDES AS POTENTIAL ANTI-AIDS DRUGS

合成了二脱氧嘧啶和嘌呤核苷 作为保护ATH8细胞免受 导致艾滋病的病毒(HIV)。5-氟-2‘，3’-二脱氧胞苷 F-ddC)与母药一样有效和具有保护作用， 二脱氧胞苷(DdC)。这种含氟化合物的碱性要低30倍。 似乎有大约三倍于口腔的 二氯甲烷在小鼠体内的生物利用度。所有其他比较显示 本质上相同的属性。将设计毒性研究 以确定5-F-ddC是否比ddC有优势。5-F-ddC也 是研究黄连药理作用的一种有用的正电子发射断层扫描药物 DDC。其他几种嘧啶二脱氧核苷已经被 为抗艾滋病检测和药理评估做准备。 二脱氧腺苷(DDA)是一种抗艾滋病药物，计划用于 87财年的临床试验。它在酸性条件下很不稳定 条件，使口服制剂药物变得困难。2‘， 3‘-二脱氧-2’-β-氟腺苷(2‘-F-Dda) 合成并发现与dda一样的活性和效力 艾滋病毒检测。此外，2‘-F-Dda在此之后不发生分解 24小时的酸性条件，使DDA的半衰期为 35秒。

Dideoxypyrimidine and purine nucleosides have been synthesized as agents to protect ATH8 cells from the cytopathic effect of the virus which causes AIDS (HIV). 5-Fluoro-2', 3'-dideoxycytidine (5- F-ddC) is as potent and protective as the parent drug, dideoxycytidine (ddC). The fluoro compound is 30 times less basic than the ddC and appears to have about three times the oral bioavailability of ddC in the mouse. All other comparisons show essentially identical properties. Toxicity studies will be designed to determine if 5-F-ddC has an advantage over ddC. 5-F-ddC also should be a useful PET scan drug for studying the pharmacology of ddC. Several other pyrimidine dideoxynucleosides have been prepared for anti-AIDS testing and pharmacological evaluation. Dideoxyadenosine (ddA) is an anti-AIDS drug scheduled for clinical trial during FY 87. It is very unstable under acidic conditions, making an oral formulation of the drug difficult. 2', 3'-dideoxy-2'-beta-fluoroadenosine (2'-F-ddA) has been synthesized and found to be just as active and potent as ddA in HIV tests. In addition, 2'-F-ddA undergoes no decomposition after 24 hours under the acidic conditions which give ddA a half-life of 35 seconds.