meta-Non-flat substituents: a novel molecular design to improve aqueous solubility in small molecule drug discovery?
Organic & Biomolecular Chemistry Pub Date: 2020-12-17 DOI: 10.1039/D0OB02083D
Abstract
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.
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Journal Name：Organic & Biomolecular Chemistry
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CAS no.: 89640-58-4
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