DIDEOXYNUCLEOSIDES AS POTENTIAL ANTI-AIDS DRUGS

双脱氧嘧啶和嘌呤核苷已被合成 作为保护ATH 8细胞免受细胞病变作用的试剂， 导致艾滋病（HIV）的病毒。 5-氟-2 '，3'-二脱氧胞苷（5- F-ddC）与母体药物一样有效和具有保护作用， 双脱氧胞苷（ddC）。 含氟化合物的碱性低30倍 比ddC，似乎有大约三倍的口服 ddC在小鼠中的生物利用度。 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是否优于ddC。 5-F-ddC还 应该是一种有用的PET扫描药物，用于研究 ddC。 几种其他的嘧啶双脱氧核苷已经被 准备进行抗艾滋病试验和药理学评价。 双脱氧腺苷（ddA）是一种抗艾滋病药物， 87财年的临床试验 在酸性条件下极不稳定 条件，使得药物的口服制剂困难。 2', 3 '-双脱氧-2'-β-氟腺苷（2 '-F-ddA）已被 合成并发现与ddA一样有效， 艾滋病毒检测。 此外，2 '-F-ddA在以下条件下不发生分解： 在酸性条件下24小时，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.