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. 2020 Jan 28;12(1):8.
doi: 10.1186/s13321-020-0412-1.

Craig plot 2.0: an interactive navigation in the substituent bioisosteric space

Peter Ertl  1
Affiliations

Craig plot 2.0: an interactive navigation in the substituent bioisosteric space

Peter Ertl. J Cheminform. .

Abstract

Bioisosteric replacement is a standard technique that is used in medicinal chemistry to design analogs of bioactive molecules with similar biological activity and with additional improved characteristics. Successful application of this technique relies on a good knowledge of physicochemical properties of common organic substituents and an efficient way to navigate their space. In this study the properties of the most common substituents present in bioactive molecules are analysed and a freely-available web tool https://bit.ly/craigplot that allows visualization, analysis and selection of bioisosteric substituents is presented.

Keywords: Bioisosteric design; Chemical space; Craig plot; Hammett sigma constant; Hansch–Fujita pi parameter; Visualisation.

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Conflict of interest statement

The author declares that he has no competing interests.

Figures

Fig. 1
Fig. 1
The web interface
Fig. 2
Fig. 2
Craig plot 2.0—visualization of logP and Hammett constants of the 26 substituents used in the original Craig paper [2]
Fig. 3
Fig. 3
The most common substituents extracted from bioactive molecules in ChEMBL. The number indicates the percentage of molecules having this substituent
See this image and copyright information in PMC

References

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    1. Ertl P. Physicochemical properties. In: Brown N, editor. Bioisosteres in medicinal chemistry. Weinheim: Wiley; 2012. pp. 129–139.