Beauchamp L M, Dolmatch B L, Schaeffer H J, Collins P, Bauer D J, Keller P M, Fyfe J A
J Med Chem. 1985 Aug;28(8):982-7. doi: 10.1021/jm00146a002.
A group of compounds was prepared in which variations of the ring portion of the acyclovir (ACV) structure were made. These modifications included monocyclic (isocytosine, triazole, imidazole), bicyclic (8-azapurine, pyrrolo[2,3-d]pyrimidine, pyrazolo[3,4-d]pyrimidine) and tricyclic (linear benzoguanine) congeners. The derivatives were evaluated against herpes simplex virus type 1 (HSV-1) by the plaque-inhibition and plaque-reduction methods with only the 8-azapurine analogue 28 showing some activity. In a test measuring the ability of these compounds to inhibit the HSV-1 thymidine kinase, 28 and the tricyclic derivative 38 exhibited competition with ACV for binding to the enzyme. The inability of the group to exert significant antiherpetic action is attributed to their lack of phosphorylation to the requisite triphosphate stage.
制备了一组化合物，其中对阿昔洛韦（ACV）结构的环状部分进行了变化。这些修饰包括单环（异胞嘧啶、三唑、咪唑）、双环（8-氮杂嘌呤、吡咯并[2,3-d]嘧啶、吡唑并[3,4-d]嘧啶）和三环（线性苯并鸟嘌呤）类似物。通过噬斑抑制和噬斑减少方法对这些衍生物进行了抗1型单纯疱疹病毒（HSV-1）评估，只有8-氮杂嘌呤类似物28显示出一定活性。在一项测量这些化合物抑制HSV-1胸苷激酶能力的试验中，28和三环衍生物38表现出与ACV竞争结合该酶。该组化合物无法发挥显著的抗疱疹作用归因于它们缺乏磷酸化至必需的三磷酸阶段。
