SYNTHESIS OF CERTAIN AZOLO [1,3] OXAZINE NUCLEOSIDES

某些偶氮[1,3]恶嗪核苷的合成

• 批准号: 3168125
• 负责人: LEROY B. TOWNSEND
• 金额: $ 10.97万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-08-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3168125
• 关键词: adenosine deaminase; adenosine kinase; azoles; bicyclic compound; chemical structure function; drug design /synthesis /production; drug screening /evaluation; guanosine; hypoxanthine phosphoribosyltransferase; inosine; nucleoside analog; oxazine; purine nucleoside phosphorylase; tubercidin; uridine

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.

拟议研究的目标将是综合某些 双环二唑并[1，3]恶嗪核苷 核苷 这项研究将提供类似的自然发生的 核苷（肌苷，腺苷，鸟苷和黄苷），然后将 作为腺苷酶的底物和/或抑制剂进行试验 脱氨酶，腺苷激酶，嘌呤核苷磷酸化酶 （PNTR）和次黄嘌呤-鸟嘌呤磷酸核糖基转移酶（HGPRT酶）。 如有必要，将合成其他衍生物， 建立构效关系。 物理化学研究 包括互变异构形式、pKa等，将努力 将这些因素中的一些与它们的生物学和化学治疗相关联 活动 这些核苷也将作为抗癌剂进行评价 体外（内部）和体内（NCI）。 还将进行研究 为了确定这些核苷是否像嘌呤一样 化合物、嘧啶样化合物或可能作为药物的前药。 我们将用它作为我们的起始原料。

项目成果

Synthetic approaches to the guanosine and xanthosine analogues 5-amino-3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazin-7-one and 3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazine-5,7-dione and studies of their antitumor potential.

鸟苷和黄苷类似物 5-氨基-3-β-D-呋喃核糖基吡唑并[3,4-e][1,3]恶嗪-7-酮和 3-β-D-呋喃核糖基吡唑并[3,4-e]的合成方法

• DOI: 10.1021/jm00111a005
• 发表时间: 1991
• 期刊: Journal of medicinal chemistry
• 影响因子: 7.3
• 作者: Zou,RM;Beylin,VG;Groziak,MP;Wotring,LL;Townsend,LB
• 通讯作者: Townsend,LB

Expression of human malaria parasite purine nucleoside phosphorylase in host enzyme-deficient erythrocyte culture. Enzyme characterization and identification of novel inhibitors.

人疟疾寄生虫嘌呤核苷磷酸化酶在宿主酶缺陷红细胞培养物中的表达。

• 发表时间: 1986
• 期刊: The Journal of biological chemistry
• 作者: Daddona,PE;Wiesmann,WP;Milhouse,W;Chern,JW;Townsend,LB;Hershfield,MS;Webster,HK
• 通讯作者: Webster,HK

Synthesis and biological activity of a novel adenosine analogue, 3-beta-D-ribofuranosylthieno[2,3-d]pyrimidin-4-one.

新型腺苷类似物 3-β-D-呋喃核糖基噻吩并[2,3-d]嘧啶-4-酮的合成和生物活性。

• DOI: 10.1021/jm00382a006
• 发表时间: 1985
• 期刊: Journal of medicinal chemistry
• 影响因子: 7.3
• 作者: Patil,VD;Wise,DS;Wotring,LL;Bloomer,LC;Townsend,LB
• 通讯作者: Townsend,LB