Development of BN Heterocycles for Biomedical Research

用于生物医学研究的氮化硼杂环化合物的开发

• 批准号: 8518381
• 负责人: Shih-Yuan Liu
• 金额: $ 28.41万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8518381
• 关键词: Address; Amino Acids; Aromatic Compounds; Attenuated; Basic Science; Behavior; Benzene; Binding; Biochemical; Biological; Biology; Biomedical Research; Boron; Cations; Chemicals; Chemistry; Development; Drug resistance; Electron Transport; Engineering; Environment; Exhibits; Family; Goals; Growth; Indoles; Investigation; Knowledge; Life; Magnetism; Methods; Modeling; Molecular; Muramidase; Nitrogen; Organism; Pharmaceutical Preparations; Phenylalanine; Positioning Attribute; Preparation; Property; Proteins; Research; Scheme; Shapes; Structure; Structure-Activity Relationship; Synthesis Chemistry; System; Time; Tryptophan; Tryptophan Synthase; Work; base; design; drug development; fitness; improved; interest; novel; pathogen; pharmacophore; programs; public health relevance; research and development; tool

DESCRIPTION (provided by applicant): Boron-containing compounds have recently emerged as useful biologically active substances with unique mechanisms of action. This proposal describes a program in synthetic chemistry geared toward developing boron-nitrogen-containing heterocycles (BN heterocycles) for use in biomedical research. Specifically, we are interested in 1,2-azaborine heterocycles, which are aromatic compounds isosteric with arenes. The broad utility and fundamental importance of arenes combined with the unique elemental and chemical features of boron make 1,2-azaborines attractive targets for biomedical investigations. Potential benefits of research into boron-based drugs include discovery of novel boron-specific mechanisms of biological activity that are unattainable by conventional organic molecules and attenuated development of drug resistance by targeted pathogens. We outline a synthetic program for the preparation of 1,2-azaborine derivatives, a physical organic program that uses a combined synthetic, structural, spectroscopic, and computational approach to address the aromaticity and reactivity of 1,2-azaborines, and a chemical biology program to establish the reactivity and interactions of BN heterocycles in a biological environment. Our proposed studies will enhance the fundamental understanding of the structure, bonding, and aromaticity the 1,2-azaborine heterocycle and illuminate the changes in the properties of classic aromatic organic molecules (e.g., benzene and indole) upon the replacement of a C=C bond with the isostructural inorganic B-N unit. The basic science resulting from the proposed work will bring new impetus to the chemistry of novel aromatics while at the same time promote the design and development of new boron-derived biologically active compounds with improved pharmacological profiles and new mechanistic tools for chemical biology. PUBLIC HEALTH RELEVANCE: This proposal describes a program in synthetic chemistry geared toward developing boron-nitrogen-containing heterocycles (BN heterocycles) for use in biomedical research. Potential benefits of research into boron-based drugs include discovery of novel boron-specific mechanisms of biological activity that are unattainable by conventional organic molecules and attenuated development of drug resistance by targeted pathogens. The proposed basic research will yield new fundamental knowledge and promote the design and development of new boron-derived biologically active compounds with improved pharmacological profiles.

描述（由申请人提供）：含硼的化合物最近已成为具有独特作用机理的有用的生物活性物质。该提案描述了一项旨在开发含硼氮的杂环（BN杂环）的合成化学计划。具体而言，我们对1,2-氮杂核杂环感兴趣，这是芳族化合物与竞技场的芳香化合物。竞技场的广泛效用和基本重要性与硼的独特元素和化学特征相结合，使生物医学研究具有1,2-azaborines的吸引人目标。对基于硼的药物的研究的潜在好处包括发现新型的硼特异性生物学活性机制，这些机制是通过常规有机分子无法实现的，并且靶向病原体对耐药性的发展减弱。我们概述了一个合成程序，用于制备1,2-亚恰当衍生物，该程序使用合成的合成，结构，光谱和计算方法来解决1,2- azaborines的芳香性和反应性，以及一种化学生物学程序来建立BN Heterogodiccles in Ateryodododics oficology Eromity oferications。我们提出的研究将增强对结构，键合和芳香性的基本理解，1,2-氮杂型杂环并阐明与等于ISROCTURATIAL INORETARINE INTORINARINGAIN ININGARINGAIN BN NITIT替换C = C键的经典芳香有机分子（例如苯和吲哚）的特性的变化。拟议工作所产生的基础科学将为新型芳香剂化学带来新的动力，同时促进具有改进的药理学特征和化学生物学的新机械工具的新型硼衍生的生物学活性化合物的设计和开发。 公共卫生相关性：该提案描述了一项旨在开发含硼氮的杂环（BN杂环）的合成化学方案。对基于硼的药物的研究的潜在好处包括发现新型的硼特异性生物学活性机制，这些机制是通过常规有机分子无法实现的，并且靶向病原体对耐药性的发展减弱。拟议的基础研究将产生新的基本知识，并促进具有改进的药理学特征的新的硼衍生的生物学活性化合物的设计和开发。