Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany.
Faculty of Chemistry, Chemical Biology Technical University Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany.
J Med Chem. 2023 Sep 28;66(18):12739-12750. doi: 10.1021/acs.jmedchem.3c00689. Epub 2023 Aug 31.
The fraction of sp-hybridized carbons () and the fraction of stereogenic carbons () are two widely employed scores of molecular complexity with strong links to biologically relevant features. However, they do not comprehensively express molecular topology, and they often do not match the chemical intuition of complexity. We propose the spacial score (SPS) as an empirical scoring system that builds upon the principle underlying and and expresses the spacial complexity of a compound in a uniform manner on a highly granular scale. The size-normalized SPS (nSPS) can differentiate distributions of natural products and synthetic compounds and is applicable in the analysis of biological activity data. Analysis of the ChEMBL database revealed general trends of increasing selectivity and potency with increasing nSPS. SPS can also be used advantageously in planning and analysis of synthesis programs for direct comparison of chemical transformations and intermediates in reaction sequences.
sp-杂化碳原子分数（）和手性碳原子分数（）是两个广泛应用于与生物相关特征具有强关联的分子复杂性的指标。然而，它们不能全面地表达分子拓扑，并且它们通常与复杂性的化学直觉不匹配。我们提出了空间分数（SPS）作为一个经验评分系统，它基于和的原理，并以高度细化的方式统一表达化合物的空间复杂性。归一化的空间分数（nSPS）可以区分天然产物和合成化合物的分布，并且适用于生物活性数据的分析。对 ChEMBL 数据库的分析揭示了随着 nSPS 的增加，选择性和效力逐渐增加的一般趋势。SPS 还可以在合成计划的规划和分析中有利地使用，以便直接比较反应序列中的化学转化和中间体。
