SYNTHESIS OF BIOLOGICALLY SIGNIFICANT INDOLES

具有生物学意义的吲哚的合成

• 批准号: 3755728
• 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/3755728
• 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引入4-氧代-3- 喹啉羧酸--一类新型高效抗菌剂 也称为“4-喹诺酮类”。含胺取代基的吲哚 所有可能的环位置都将被合成并用作 潜在抗菌剂的前体。这些凝结在一起 带有β-二羰基加合物的氨基吲哚将提供丙烯酸酯 可以环合成最终的4-喹诺酮结构。抗菌剂 药敏试验将在子项目的主持下进行 2(乔普拉博士)。 我们还将尝试用结构类似物制备褪黑激素类似物 国家癌症研究所(NCI)研究人员建议的修改 根据目前对细胞有丝分裂抑制的测试结果。 这些新化合物也将作为细胞提交给NCI进行测试 有丝分裂抑制药。我们还希望评估反应的范围。 含有亚硫酸氢钠的吲哚的潜在意义 吲哚和药物化学。 为了完成这项工作，我们打算让本科生参加 这些化合物的合成和表征的方方面面 将利用至少12种不同类型的化学品的化合物 反应，其中一些可能是第一次应用于特定的 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进行检查，这可能证明 有这样的理由。