Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
Org Biomol Chem. 2021 Jan 21;19(2):446-456. doi: 10.1039/d0ob02083d.
Aqueous solubility is a key requirement for small-molecule drug candidates. Here, we investigated the regioisomer-physicochemical property relationships of disubstituted benzenes. We found that meta-isomers bearing non-flat substituents tend to possess the lowest melting point and the highest thermodynamic aqueous solubility among the regioisomers. The examination of pharmaceutical compounds containing a disubstituted benzene moiety supported the idea that the introduction of a non-flat substituent at the meta position of a benzene substructure would be a promising approach for medicinal chemists aiming to improve the thermodynamic aqueous solubility of drug candidates, even though it might not be universally effective.
水溶性是小分子药物候选物的关键要求。在这里，我们研究了二取代苯的位置异构体-物理化学性质关系。我们发现，带有非平面取代基的间位异构体往往具有最低的熔点和最高的热力学水溶性。含有二取代苯部分的药物化合物的考察支持了这样一种观点，即在苯亚结构的间位引入非平面取代基对于旨在提高药物候选物热力学水溶性的药物化学家来说是一种有前途的方法，尽管它可能不是普遍有效的。
