SYNTHESIS OF CERTAIN AZOLO [1,3] OXAZINE NUCLEOSIDES

拟议研究的目标将是综合某些 双环重氮并[1，3]恶嗪核苷从适当的单环中分离出来 核苷。这项研究将提供与自然发生的 核苷(肌苷、腺苷、鸟苷和黄苷)，然后 被测试为腺苷酶的底物和/或抑制剂 脱氨酶、腺苷激酶、嘌呤核苷磷酸化酶 (PNPase)和次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HGPRTase)。 将根据需要合成更多的衍生品，以便 建立一种结构活动关系。物理化学研究 涉及互变异构体、PKA等，将努力 这些因素中的一些与它们的生物和化学治疗作用有关 活动。这些核苷也将被评估为抗癌药物。 体外(室内)和体内(NCI)。此外，还将进行研究 为了确定这些核苷是否起到了类似嘌呤的作用 化合物，嘧啶类化合物，或者可能作为一种前药 单环核苷，我们将使用它作为我们的起始材料。

The objective of the proposed research will be to synthesize certain bicyclic diazolo[1,3]oxazine nucleosides from the appropriate monocyclic nucleosides. This study will provide analogs of the naturally occurring nucleosides (inosine, adenosine, guanosine and xanthosine), which will then be tested as substrates and/or inhibitors of the enzymes adenosine deaminase (ADase), adenosine kinase, purine nucleoside phosphorylase (PNPase), and hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). Additional derivatives will be synthesized as deemed necessary in order to establish a structure activity relationship. Physico-chemical studies involving tautomeric forms, pKa's, etc., will be undertaken in efforts to correlate some of these factors with their biological and chemotherapeutic activity. These nucleosides will also be evaluated as anticancer agents both in vitro (in house) and in vivo (NCI). Studies will also be conducted in order to determine if these nucleosides are acting as purine-like compounds, pyrimidine-like compounds or perhaps as a pro-drug of the monocyclic nucleosides which we will be using as our starting materials.