Guasch Laura, Yapamudiyansel Waruna, Peach Megan L, Kelley James A, Barchi Joseph J, Nicklaus Marc C
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland 21702, United States.
Basic Science Program, Chemical Biology Laboratory, Leidos Biomedical Inc., Frederick National Laboratory for Cancer Research , Frederick, Maryland 21702, United States.
J Chem Inf Model. 2016 Nov 28;56(11):2149-2161. doi: 10.1021/acs.jcim.6b00338. Epub 2016 Oct 16.
We investigated how many cases of the same chemical sold as different products (at possibly different prices) occurred in a prototypical large aggregated database and simultaneously tested the tautomerism definitions in the chemoinformatics toolkit CACTVS. We applied the standard CACTVS tautomeric transforms plus a set of recently developed ring-chain transforms to the Aldrich Market Select (AMS) database of 6 million screening samples and building blocks. In 30 000 cases, two or more AMS products were found to be just different tautomeric forms of the same compound. We purchased and analyzed 166 such tautomer pairs and triplets by H and C NMR to determine whether the CACTVS transforms accurately predicted what is the same "stuff in the bottle". Essentially all prototropic transforms with examples in the AMS were confirmed. Some of the ring-chain transforms were found to be too "aggressive", i.e. to equate structures with one another that were different compounds.
我们研究了在一个典型的大型汇总数据库中，作为不同产品（可能价格也不同）出售的同一种化学品出现了多少案例，并同时测试了化学信息学工具包CACTVS中的互变异构定义。我们将标准的CACTVS互变异构转换以及一组最近开发的环链转换应用于包含600万个筛选样本和构建模块的Aldrich市场精选（AMS）数据库。在30000个案例中，发现两种或更多的AMS产品只是同一化合物的不同互变异构形式。我们通过氢和碳核磁共振购买并分析了166对这样的互变异构体对和三联体，以确定CACTVS转换是否准确预测了“瓶子里的东西”是相同的。基本上，AMS中所有具有示例的质子转移转换都得到了证实。发现一些环链转换过于“激进”，即把不同化合物的结构彼此等同起来。
