Insilico Medicine Hong Kong Limited (previously Insilico Medicine, Inc.) , Unit 307A, Core Building 1, 1 Science Park East Avenue, Hong Kong Science Park , Pak Shek Kok , Hong Kong.
Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre , Oktyabrya Prospekt 71 , Ufa 450054 , Russian Federation.
J Med Chem. 2019 Nov 27;62(22):10026-10043. doi: 10.1021/acs.jmedchem.9b00004. Epub 2019 Jun 26.
The paradigm of "drug-like-ness" dramatically altered the behavior of the medicinal chemistry community for a long time. In recent years, scientists have empirically found a significant increase in key properties of drugs that have moved structures closer to the periphery or the outside of the rule-of-five "cage". Herein, we show that for the past decade, the number of molecules claimed in patent records by major pharmaceutical companies has dramatically decreased, which may lead to a "chemical singularity". New compounds containing fragments with increased 3D complexity are generally larger, slightly more lipophilic, and more polar. A core difference between this study and recently published papers is that we consider the nature and quality of sp-rich frameworks rather than sp count. We introduce the original descriptor MCE-18, which stands for medicinal chemistry evolution, 2018, and this measure can effectively score molecules by novelty in terms of their cumulative sp complexity.
“类药性”范式在很长一段时间内极大地改变了药物化学界的行为。近年来，科学家们从经验上发现，那些结构更接近“五规则”“笼子”外围的药物的关键性质有了显著提高。在此，我们表明，在过去十年中，大型制药公司在专利记录中声称的分子数量大幅减少，这可能导致“化学奇点”。含有增加 3D 复杂度片段的新化合物通常更大、略亲脂性、极性更强。本研究与最近发表的论文的核心区别在于，我们考虑的是富硫框架的性质和质量，而不是 sp 计数。我们引入了原始描述符 MCE-18，它代表药物化学进化，2018，这个度量可以有效地根据它们的累积 sp 复杂度的新颖性对分子进行评分。
