Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing
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 w...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383523004446 |
| _version_ | 1797271332231053312 |
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| author | Tongyu Huo Xinyi Zhao Zengrui Cheng Jialiang Wei Minghui Zhu Xiaodong Dou Ning Jiao |
| author_facet | Tongyu Huo Xinyi Zhao Zengrui Cheng Jialiang Wei Minghui Zhu Xiaodong Dou Ning Jiao |
| author_sort | Tongyu Huo |
| collection | DOAJ |
| description | 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 elements into bioactive compounds promptly. Such modifications alter the chemical space and physiochemical 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 components 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 functionalized 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. |
| first_indexed | 2024-03-07T14:02:09Z |
| format | Article |
| id | doaj.art-80061318a85c4fe486569719e3a606ea |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-07T14:02:09Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-80061318a85c4fe486569719e3a606ea2024-03-07T05:27:34ZengElsevierActa Pharmaceutica Sinica B2211-38352024-03-0114310301076Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editingTongyu Huo0Xinyi Zhao1Zengrui Cheng2Jialiang Wei3Minghui Zhu4Xiaodong Dou5Ning Jiao6State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Changping Laboratory, Beijing 102206, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Corresponding authors.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; Corresponding authors.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 elements into bioactive compounds promptly. Such modifications alter the chemical space and physiochemical 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 components 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 functionalized 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.http://www.sciencedirect.com/science/article/pii/S2211383523004446Late-stage modificationDrug spaceHalogenationOxygenationNitrogenationSynthetic chemistry |
| spellingShingle | Tongyu Huo Xinyi Zhao Zengrui Cheng Jialiang Wei Minghui Zhu Xiaodong Dou Ning Jiao Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing Acta Pharmaceutica Sinica B Late-stage modification Drug space Halogenation Oxygenation Nitrogenation Synthetic chemistry |
| title | Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing |
| title_full | Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing |
| title_fullStr | Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing |
| title_full_unstemmed | Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing |
| title_short | Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing |
| title_sort | late stage modification of bioactive compounds improving druggability through efficient molecular editing |
| topic | Late-stage modification Drug space Halogenation Oxygenation Nitrogenation Synthetic chemistry |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523004446 |
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