Late-stage modification of bioactive compounds:Improving druggability through efficient molecular editing

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外文摘要：Synthetic chemistry plays an indispensable role in drug discovery,contributing to hit compounds identification,lead compounds optimization,candidate drugs preparation,and so on.As Nobel Prize laureate James Black emphasized,"the most fruitful basis for the discovery of a new drug is to start with an old drug"1.Late-stage modification or functionalization of drugs,natural products and bioactive compounds have garnered significant interest due to its ability to introduce diverse ele-ments into bioactive compounds promptly.Such modifications alter the chemical space and physio-chemical properties of these compounds,ultimately influencing their potency and druggability.To enrich a toolbox of chemical modification methods for drug discovery,this review focuses on the incorporation of halogen,oxygen,and nitrogen—the ubiquitous elements in pharmacophore compo-nents of the marketed drugs—through late-stage modification in recent two decades,and discusses the state and challenges faced in these fields.We also emphasize that increasing cooperation between chemists and pharmacists may be conducive to the rapid discovery of new activities of the functiona-lized molecules.Ultimately,we hope this review would serve as a valuable resource,facilitating the application of late-stage modification in the construction of novel molecules and inspiring innovative concepts for designing and building new drugs.

外文关键词：

Late-stage modificationDrug spaceHalogenationOxygenationNitrogenationSynthetic chemistry

作者：

Tongyu Huo、Xinyi Zhao、Zengrui Cheng、Jialiang Wei、Minghui Zhu、Xiaodong Dou、Ning Jiao

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作者单位：

State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China

Changping Laboratory,Beijing 102206,China

Shanghai Key Laboratory of Green Chemistry and Chemical Processes,East China Normal University,Shanghai 200062,China

基金：

国家重点研发计划国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金Ministry of Science and Technology of China Changping Laboratory,Peking University Special Fund for COVID-19New Cornerstone Science Foundation through the XPLORER PRIZE are greatly appreciated

项目编号：

2021YFA150170022293014221310022216114201981821004

出版年：

2024

DOI：

10.1016/j.apsb.2023.11.021

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(3)

参考文献量420