ИСТИНА

The paradigm of “drug likeness” dramatically influenced 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 beyond the rule-of-five. Herein, we show that for the past decade, the number of molecules claimed in patents by Big Pharma companies has dramatically decreased, which may lead to a “chemical singularity”. New compounds with increased 3D complexity are generally larger, slightly more lipophilic and polar. A core difference between this study and recently published papers is that we consider the nature and quality of sp3-rich frameworks rather than sp3 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 sp3 complexity.