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ABSTRACT: BACKGROUND: A method to estimate ease of synthesis (synthetic accessibility) of drug-like molecules is needed in many areas of the drug discovery process. The development and validation of such a method that is able to characterize molecule synthetic accessibility as a score between 1 (easy to make) and 10 (very difficult to make) is described in this article. RESULTS: The method for estimation of the synthetic accessibility score (SAscore) described here is based on a combination of fragment contributions and a complexity penalty. Fragment contributions have been calculated based on the analysis of one million representative molecules from PubChem and therefore one can say that they capture historical synthetic knowledge stored in this database. The molecular complexity score takes into account the presence of non-standard structural features, such as large rings, non-standard ring fusions, stereocomplexity and molecule size. The method has been validated by comparing calculated SAscores with ease of synthesis as estimated by experienced medicinal chemists for a set of 40 molecules. The agreement between calculated and manually estimated synthetic accessibility is very good with r2 = 0.89. CONCLUSION: A novel method to estimate synthetic accessibility of molecules has been developed. This method uses historical synthetic knowledge obtained by analyzing information from millions of already synthesized chemicals and considers also molecule complexity. The method is sufficiently fast and provides results consistent with estimation of ease of synthesis by experienced medicinal chemists. The calculated SAscore may be used to support various drug discovery processes where a large number of molecules needs to be ranked based on their synthetic accessibility, for example when purchasing samples for screening, selecting hits from high-throughput screening for follow-up, or ranking molecules generated by various de novo design approaches.

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As part of a project I was wondering about reports of surveys that collected chemists assessments of differnt things. More specifically, I wasn’t looking for crowd-sourcing efforts for data curation (such as the in the Spectral Game) or data collection....
After screening a panel of substances for activity, one of the most important questions to answer revolves around the relative synthetic accessibility of the most interesting hits. Synthetic accessibility is critical in both re-synthesis of hits and in preparing...
After screening a panel of substances for activity, one of the most important questions to answer revolves around the relative synthetic accessibility of the most interesting hits. Synthetic accessibility is critical in both re-synthesis of hits and in preparing...
Take a look at our ten most accessed papers for January.The most accessed article last month describes the implementation of a Chemically Aware system to supplement the content management program, SharePoint. The system allows users to tag documents by drawing...
Take a look at our ten most accessed articles for September.The majority of the highly accessed articles last month were published in Journal of Cheminformatics, and include Shoba Ranganathans comparative analysis of pharmaceutically relevant datasets, as well...