ANTITUMOR AND ANTIVIRAL NUCLEOSIDE ANALOGS

抗肿瘤和抗病毒核苷类似物

• 批准号: 3170634
• 负责人: JIRI ZEMLICKA
• 金额: $ 15.8万
• 依托单位: BARBARA ANN KARMANOS CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3170634
• 关键词: adenosine; antiviral agents; cytidine; drug design /synthesis /production; nucleoside analog

Novel nucleoside analogs will be prepared and studied as potential antitumor and antiviral agents. These compounds will include: (i) "Hydroxycarbocyclic" analogs of adenosine and cytidine, (ii) Hydroxycarbocyclic analogs of antitumor and antiviral agents araC [Cytarabine, 1-(Beta-D-arabinofuranosyl)cytosine] and araA [Vidarabine, 9-(Beta-D-arabinofuranosyl)-adenine] related to the neplanocin group of antitumor nucleoside antibiotics, and (iii) neplanocin A (NPC-A) and the corresponding cytidine analog. All compounds will be obtained by chemical synthesis using anti-7-tert-butoxy-5-norbornene-exo-cis-2,3-diol as a key common intermediate. Antitumor activity and mechanism of action of NPC-A and synthetic analogs will be studied in vitro and in vivo in murine leukemia L1210, P388, and sixteen solid tumor systems. Particular attention will be paid to (i) inhibition of macromolecular synthesis, (ii) reversal studies with specific metabolites, (iii) alterations in nucleotide pool sizes, and (iv) effects on RNA maturation. Antiviral activity of the nucleoside analogs will also be investigated.

新颖的核苷类似物将被准备并研究为电势 抗肿瘤和抗病毒药物。 这些化合物将包括：（i） 腺苷和胞丁的“羟基钙循环”类似物，（ii） 抗肿瘤和抗病毒药物ARAC的羟基核细胞类似物 [Cytarabine，1-（β-D-阿拉伯呋喃糖基）胞嘧啶]和Araa [Vidarabine， 9-（β-D-阿拉伯呋喃糖基） - 腺嘌呤]与Neplanocin组有关 抗肿瘤核苷抗生素和（III）内皮素A（NPC-A）和（NPC-A）和 相应的胞苷类似物。 所有化合物将通过化学品获得 使用抗7-TERT-butoxy-5-norbornen-exo-Cis-2,3-二醇合成 普通中间体。 NPC-A和合成类似物的抗肿瘤活性和作用机理 将在体外和体内研究鼠白血病L1210，p388和 十六个实体瘤系统。 特别关注（i） 抑制大分子合成，（ii）特定的逆转研究 代谢物，（iii）核苷酸池大小的改变，（iv）效应 关于RNA成熟。 核苷类似物的抗病毒活性也将 被调查。