New Iridium-catalysed Methods for C-H Activation and Hydrogen-Isotope Exchange towards Labelled Oligonucleotides and Other Heterocycles
用于标记寡核苷酸和其他杂环的 C-H 激活和氢同位素交换的新铱催化方法
基本信息
- 批准号:2268769
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:英国
- 项目类别:Studentship
- 财政年份:2019
- 资助国家:英国
- 起止时间:2019 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
New Iridium-catalysed Methods for C-H Activation and Hydrogen-Isotope Exchange towards Labelled Oligonucleotides and Other Heterocycles of Elevated Importance in Drug Discovery.Recently established iridium species from the Kerr laboratories at Strathclyde have emerged to become some of the most active species in isotope labelling chemistry, an area of significant importance within drug design and synthesis. Building on these studies, it is now proposed that, as part of extended collaborations with AstraZeneca, this field of iridium catalysis is further and extensively diversified, in terms of catalyst structure, key substrate scope, and mode of labelling. The objectives of this research project are to:- Extend the recently-developed sp3 labelling towards oligonucleotide units of direct importance and relevance to AstraZeneca;- Expand directed sp2 labelling to an appreciably broader range of pharmaceutically-important N-heterocycles; and- Develop a general and presently sought-after method for the non-directed, C-2 labelling of pyridines.The research described in this programme of work will deliver a flexible range of stable, highly active catalysts of appreciable utility in ongoing selective and functional group tolerant C-H activation and hydrogen isotope exchange processes. Capitalising on emerging techniques from Strathclyde laboratories, a variety of labelled new chemical entities will become accessible via this collaborative research project. More specifically, this will include extremely valuable and selectively labelled oligonucleotide units, as well as a series of heterocycles of elevated pharmaceutical importance and potential application in bioconjugation processes. As part of these research approaches and as routinely applied within our laboratory in this area, the application of computational methods combined with experimental mechanistic modelling and kinetic studies will form a core component of this programme.
新的铱催化C-H活化和氢同位素交换方法在药物发现中具有重要意义的标记寡核苷酸和其他杂环。最近在斯特拉斯克莱德克尔实验室建立的铱物种已经成为同位素标记化学中最活跃的物种,这是药物设计和合成中一个重要的领域。在这些研究的基础上,现在建议,作为与阿斯利康扩展合作的一部分,在催化剂结构、关键底物范围和标记模式方面,该领域的铱催化将进一步广泛多样化。该研究项目的目标是:-将最近开发的sp3标签扩展到与阿斯利康直接重要和相关的寡核苷酸单位;-将定向sp2标签扩展到更广泛的具有重要药用价值的n -杂环;开发一种通用的、目前广受欢迎的非定向、C-2标记吡啶的方法。本项目所描述的研究将提供一系列稳定、高活性的催化剂,在持续的选择性和官能团耐受C-H活化和氢同位素交换过程中具有可观的效用。利用斯特拉斯克莱德实验室的新兴技术,各种标记的新化学实体将通过这个合作研究项目获得。更具体地说,这将包括极有价值和选择性标记的寡核苷酸单位,以及一系列具有提高药物重要性和潜在应用于生物偶联过程的杂环。作为这些研究方法的一部分,以及我们实验室在该领域的常规应用,将计算方法与实验机械建模和动力学研究相结合的应用将构成本课程的核心组成部分。
项目成果
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其他文献
吉治仁志 他: "トランスジェニックマウスによるTIMP-1の線維化促進機序"最新医学. 55. 1781-1787 (2000)
Hitoshi Yoshiji 等:“转基因小鼠中 TIMP-1 的促纤维化机制”现代医学 55. 1781-1787 (2000)。
- DOI:
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LiDAR Implementations for Autonomous Vehicle Applications
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
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吉治仁志 他: "イラスト医学&サイエンスシリーズ血管の分子医学"羊土社(渋谷正史編). 125 (2000)
Hitoshi Yoshiji 等人:“血管医学与科学系列分子医学图解”Yodosha(涉谷正志编辑)125(2000)。
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Effect of manidipine hydrochloride,a calcium antagonist,on isoproterenol-induced left ventricular hypertrophy: "Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,K.,Teragaki,M.,Iwao,H.and Yoshikawa,J." Jpn Circ J. 62(1). 47-52 (1998)
钙拮抗剂盐酸马尼地平对异丙肾上腺素引起的左心室肥厚的影响:“Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,
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