ENZYME INHIBITORS AS PROTENTIAL ANTICANCER AND ANTIVIRAL DRUGS

1-（2 '-脱氧-BETA-D-呋喃核糖基）-1，2-二氢嘧啶-2-酮-5'- 一磷酸（2 '-脱氧zebularine一磷酸）被鉴定为一种非常 脱氧胞苷酸脱氨酶的有效抑制剂。 母体核苷是 通过新的合成方法制备。 一个大规模的适应 2 ′-脱氧zebularine的合成工作良好。 合成5 '- 生物学测试中所需的足够量的单磷酸盐， 中求进工作总 与5 '-单磷酸酯的比较研究 四氢尿苷的计划。 已经合成了大量的单-和双-丁内酯， 在它们激活的方式上显示出非常立体选择性 蛋白激酶C（PK-C）。 这些化合物的功能是构象 甘油二酯的受限类似物。 达到的效力水平 现在是亚微摩尔的 更精确的结构活性分析是 预期产生在纳摩尔浓度下有效的化合物。 这 在PK-C的设计中，将使用结构上重要的信息 抑制剂的

1-(2'-deoxy-BETA-D-ribofuranosyl)-1,2-Dihydropyrimidine-2-one-5'- monophosphate (2'-deoxyzebularine monophosphate) was identified as a very potent inhibitor of deoxycytidilate deaminase. The parent nucleoside was prepared by a new synthetic approach. A large-scale adaptation of the synthesis of 2'-deoxyzebularine worked well. Synthesis of the 5'- monophosphate in sufficient amounts for biological testing is in progress. Comparative studies with the 5'-monophosphate of tetrahydrouridine are planned. A large number of mono- and bis-butyrolactones have been synthesized and shown to be very stereoselective in the manner in which they activate protein kinase C (PK-C). These compounds function as conformationally constrained analogues of diacylglycerol. The level of potency achieved is now submicromolar. A more refined structure-activity analysis is expected to yield compounds effective at nanomolar concentrations. This structurally vital information will be put to use in the design of PK-C inhibitors.