R-group replacement database for medicinal chemistry

Kosuke Takeuchi; Ryo Kunimoto; Jürgen Bajorath

doi:10.2144/fsoa-2021-0062

R-group replacement database for medicinal chemistry

Future Sci OA. 2021 Jun 30;7(8):FSO742. doi: 10.2144/fsoa-2021-0062. eCollection 2021 Sep.

Authors

Kosuke Takeuchi¹, Ryo Kunimoto¹, Jürgen Bajorath¹

Affiliation

¹ Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology & Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Friedrich-Hirzebruch-Allee 6, Bonn, D-53113, Germany.

Abstract

Aim: Generation of an R-group replacement system for compound optimization in medicinal chemistry.

Materials & methods: From bioactive compounds, analogue series (ASs) were systematically extracted and from these ASs, all R-groups were isolated and further analyzed.

Exemplary results & data: From more than 17,000 ASs, more than 50,000 unique R-groups were isolated. For the 500 most frequently used R-groups, preferred replacements were identified and organized in hierarchies. All original data and an R-group replacement database are made available in an open access deposition.

Limitations & next steps: The searchable database has no limitations and can easily be modified using the source data we provide. The next step will be applying this R-group resource in practical medicinal chemistry projects as decision support.

Keywords: R-groups; analogue series; compound optimization; data repository; network data structure; replacements.