Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions.
Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions.
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DOI：
10.1186/1758-2946-1-8
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发表时间：
2009-06-10
影响因子：
8.6
通讯作者：
Schuffenhauer A
中科院分区：
文献类型：
--
作者：
Ertl P;Schuffenhauer A
在药物发现过程的许多领域，需要一种估计药物样分子的合成（合成可及性）的方法。本文描述了这种方法能够将分子合成可及性表征为1（易于制作）和10（非常难以制作）的分子综合可及性的方法的开发和验证。
估计此处描述的合成可及性评分（SASCORE）的方法是基于片段贡献和复杂性惩罚的组合。片段贡献是根据对PubChem的一百万代表分子的分析进行了计算的，因此可以说它们捕获了该数据库中存储的历史合成知识。分子复杂度得分考虑了非标准结构特征的存在，例如大环，非标准环融合，立体声音和分子大小。通过将计算出的Sascore与经验丰富的药物学家对一组40个分子进行比较，该方法已通过将计算出的Sascore与易于合成的比较进行了验证。 R2 = 0.89之间的计算和手动估计合成可及性之间的一致性非常好。
已经开发了一种估计分子合成可及性的新方法。该方法使用通过分析数百万已经合成化学品和考虑的数百万个已经合成的化学物质的信息获得的历史综合知识。该方法足够快，提供了与经验丰富的药物学家估算合成易于性的结果。计算出的SASCORE可用于支持各种药物发现过程，其中需要根据其合成可及性对大量分子进行排名，例如，在购买样品进行筛选时，从高通量筛选中选择击球以进行随访或排名各种从头设计方法产生的分子。
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. 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. 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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影响因子：
5.6
作者：
Ertl, Peter;Roggo, Silvio;Schuffenhauer, Ansgar
通讯作者：
Schuffenhauer, Ansgar
影响因子：
7.3
作者：
Ertl, P;Rohde, B;Selzer, P
通讯作者：
Selzer, P
影响因子：
4
作者：
KANEMASA, S;SAKOH, H;TSUGE, O
通讯作者：
TSUGE, O
DOI：
10.1021/ci970429i
发表时间：
1998-05-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Lewell, XQ;Judd, DB;Hann, MM
通讯作者：
Hann, MM
影响因子：
3.5
作者：
Boda, Krisztina;Seidel, Thomas;Gasteiger, Johann
通讯作者：
Gasteiger, Johann