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A Close-up Look at the Chemical Space of Commercially Available Building Blocks for Medicinal Chemistry
| Title: | A Close-up Look at the Chemical Space of Commercially Available Building Blocks for Medicinal Chemistry |
| Authors: | Zabolotna, Yuliana Browse this author | | Volochnyuk, Dmitriy M. Browse this author | | V. Ryabukhin, Sergey Browse this author | | Horvath, Dragos Browse this author | | Gavrilenko, Konstantin S. Browse this author | | Marcou, Gilles Browse this author | | Moroz, Yurii S. Browse this author | | Oksiuta, Oleksandr Browse this author | | Varnek, Alexandre Browse this author |
| Keywords: | Medicinal chemistry | | Reagents,Chemical reactions | | Organic synthesis | | Anions |
| Issue Date: | 20-Dec-2021 |
| Publisher: | American Chemical Society |
| Journal Title: | Journal of chemical information and modeling |
| Volume: | 62 |
| Issue: | 9 |
| Start Page: | 2171 |
| End Page: | 2185 |
| Publisher DOI: | 10.1021/acs.jcim.1c00811 |
| Abstract: | The ability to efficiently synthesize desired compounds can be a limiting factor for chemical space exploration in drug discovery. This ability is conditioned not only by the existence of wellstudied synthetic protocols but also by the availability of corresponding reagents, so-called building blocks (BBs). In this work, we present a detailed analysis of the chemical space of 400 000 purchasable BBs. The chemical space was defined by corresponding synthonsfragments contributed to the final molecules upon reaction. They allow an analysis of BB physicochemical properties and diversity, unbiased by the leaving and protective groups in actual reagents. The main classes of BBs were analyzed in terms of their availability, rule-oftwo-defined quality, and diversity. Available BBs were eventually compared to a reference set of biologically relevant synthons derived from ChEMBL fragmentation, in order to illustrate how well they cover the actual medicinal chemistry needs. This was performed on a newly constructed universal generative topographic map of synthon chemical space that enables visualization of both libraries and analysis of their overlapped and library-specific regions. |
| Rights: | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of chemical information and modeling, copyright c American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/articlesonrequest/AOR-8I9JU9NYIEPICSWP4865 . |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/87610 |
| Appears in Collections: | 化学反応創成研究拠点：ICReDD (Institute for Chemical Reaction Design and Discovery : ICReDD) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: Alexandre Varnek
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