ENZYME INHIBITORS AS PROTENTIAL ANTICANCER AND ANTIVIRAL DRUGS

本工作继续探索机制基础的效用 对癌症化疗至关重要的酶的抑制剂。 成功的肌苷一磷酸脱氢酶抑制剂， 已经开发，未来的体内研究将尽快安排 随着大量的药物变得可用。 尽可能地合成了几种膦酸酯核苷 嘌呤核苷磷酸化酶的抑制剂，但所述化合物 不活跃。 一种含膦酸酯的2 ′，5 ′-寡腺苷酸， 三聚体被制备成酶稳定的干扰素 诱导剂。 一个制备蛋白激酶C抑制剂的项目， 甘油主链已经被引发。 这项工作旨在 定义关键的空间关系之间存在的 该酶的已知活化剂中的极性和非极性基团。

This work continues to explore the utility of mechanism-base inhibitors against enzymes critical for cancer chemotherapy. Successful inhibitors of inosine monophosphate dehydrogenase have been developed and future in vivo studies will be scheduled as soon as larger quantities of drugs become available. Several phosphonate nucleosides were synthesized as possible inhibitors of purine nucleoside phosphorylase but the compounds were inactive. A phosphonate-containing 2',5'-oligoadenylate trimer is being prepared as an enzymatically stable interferon inducer. A project to prepare protein kinase C inhibitors containing a rigid glycerol backbone has been initiated. The work is intended to define the critical spatial relationships which exist between the polar and non-polar groups in known activators of this enzyme.