Topliss Batchwise Schemes Reviewed in the Era of Open Data Reveal Significant Differences between Enzymes and Membrane Receptors
- Author(s)
- Lars Richter
- Abstract
In 1977, John G. Topliss introduced the Topliss Batchwise Scheme, a straightforward nonmathematical procedure to assist medicinal chemists in optimizing the substitution pattern of a phenyl ring. Despite its long period of application, a thorough validation of this method has been missing so far. Here, we address this issue by gathering 129 congeneric series from the ChEMBL database, suitable to retrospectively assess the approach. Frequency analysis of Topliss' schemes showed that the π, Es, σ, and σ scheme occurred in 17, 20, 6, and 4 congeneric series, respectively. We observed a significant difference of π scheme frequency in enzymes versus membrane receptors, with 12 versus only 2 occurrences. Validation of Topliss schemes in potency optimization showed a remarkable performance increase after restricting the data set to analogue series tested solely against enzymes. In this setting, the Es and the π scheme were successful in 50% and 56% of the analogue series, respectively.
- Organisation(s)
- Journal
- Journal of Chemical Information and Modeling
- Volume
- 57
- Pages
- 2575–2583
- No. of pages
- 9
- ISSN
- 1549-9596
- DOI
- https://doi.org/10.1021/acs.jcim.7b00195
- Publication date
- 10-2017
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301207 Pharmaceutical chemistry
- Keywords
- ASJC Scopus subject areas
- Chemical Engineering(all), Chemistry(all), Library and Information Sciences, Computer Science Applications
- Portal url
- https://ucris.univie.ac.at/portal/en/publications/topliss-batchwise-schemes-reviewed-in-the-era-of-open-data-reveal-significant-differences-between-enzymes-and-membrane-receptors(31930242-546f-40e4-bd9f-f05bf9cb5098).html