SYNTHESIS OF BIOLOGICALLY SIGNIFICANT INDOLES

具有生物学意义的吲哚的合成

• 批准号: 3777765
• 负责人: H F RUSSELL
• 金额: --
• 依托单位: JOHNSON C. SMITH UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3777765
• 关键词: acetylation; antibacterial agents; autoradiography; chemical structure function; drug design /synthesis /production; histochemistry /cytochemistry; hormone analog; indoleamine; indoles; ion exchange chromatography; melatonin; quinolinate

We propose to incorporate the indole moiety into 4-oxo-3- quinolinecarboxylic acids, a new class of potent antimicrobial agents also called "4-quinolones". Indoles having amine groups substituted in all possible ring positions will be synthesized and utilized as precursors of the potential antimicrobials. Condensation of these aminoindoles with beta-dicarbonyl adducts will provide acrylates which may be cyclized to the final 4-quinolone structure. Antimicrobial susceptibility testing will take place under the auspices of sub-project 2 (Dr. Chopra). We will also attempt to prepare Melatonin analogs with structural modifications as suggested by National Cancer Institute (NCI) researchers based upon the results of current testing for cell mitosis inhibition. These new compounds will also be submitted to NCI for testing as cell mitosis inhibitors. We also hope to evaluate the scope of the reaction of indoles with sodium bisulfite due to its potential significance to indole and medicinal chemistry. To accomplish this work, we intend involving undergraduate students in all aspects of the synthesis and characterization of these chemical compounds which will utilize at least 12 different types of chemical reactions some of which may be first-time applications in a specific area. The project allows room for expansion and/or more detailed examination of any particular facet of the research which may prove to warrant such.

我们建议将吲哚部分并入 4-oxo-3- 喹啉羧酸，一类新型强效抗菌剂 也称为“4-喹诺酮类”。 具有取代基胺基的吲哚 所有可能的环位置将被合成并利用为 潜在抗菌剂的前体。 这些的凝结 氨基吲哚与β-二羰基加合物将提供丙烯酸酯， 可以环化成最终的4-喹诺酮结构。 抗菌 敏感性测试将在子项目的主持下进行 2（乔普拉博士）。 我们还将尝试制备具有结构的褪黑素类似物 根据美国国家癌症研究所 (NCI) 研究人员的建议进行修改 基于当前细胞有丝分裂抑制测试的结果。 这些新化合物也将提交给 NCI 进行细胞测试 有丝分裂抑制剂。 我们也希望评估反应的范围 吲哚与亚硫酸氢钠的潜在意义 吲哚和药物化学。 为了完成这项工作，我们打算让本科生参与 这些化学品的合成和表征的各个方面 将使用至少 12 种不同类型化学品的化合物 反应其中一些可能是特定领域的首次应用 区域。 该项目允许扩展和/或更详细的空间 对研究的任何特定方面的检查可能证明 保证这样的。