Pitt William R, Parry David M, Perry Benjamin G, Groom Colin R
UCB Celltech, Granta Park, Great Abington, Cambridge CB15 6GS, United Kingdom.
J Med Chem. 2009 May 14;52(9):2952-63. doi: 10.1021/jm801513z.
Small aromatic ring systems are of central importance in the development of novel synthetic protein ligands. Here we generate a complete list of 24,847 such ring systems. We call this list and associated annotations VEHICLe, which stands for virtual exploratory heterocyclic library. Searches of literature and compound databases, using this list as substructure queries, identified only 1701 as synthesized. Using a carefully validated machine learning approach, we were able to estimate that the number of unpublished, but synthetically tractable, VEHICLe rings could be over 3000. However, analysis also shows that the rate of publication of novel examples to be as low as 5-10 per year. With this work, we aim to provide fresh stimulus to creative organic chemists by highlighting a small set of apparently simple ring systems that are predicted to be tractable but are, to the best of our knowledge, unconquered.
小型芳香环系统在新型合成蛋白质配体的开发中至关重要。在此，我们生成了一份包含24,847个此类环系统的完整列表。我们将此列表及相关注释称为VEHICLe，即虚拟探索性杂环文库的缩写。以该列表作为子结构查询条件对文献和化合物数据库进行检索，结果显示仅有1701个已被合成。通过一种经过精心验证的机器学习方法，我们能够估计出尚未发表但具有合成可行性的VEHICLe环的数量可能超过3000个。然而，分析还表明，新实例的发表速率低至每年5 - 10个。通过这项工作，我们旨在通过突出一小部分看似简单但据我们所知尚未被攻克且预计具有合成可行性的环系统，为富有创造力的有机化学家提供新的激励。
