Meta-Non-flat substituents: a novel molecular design to improve aqueous solubility in small molecule drug discovery. Issue 2 (17th December 2020)

• Record Type: Journal Article
• Authors: Ichikawa, Yuki; Hiramatsu, Michiaki; Mita, Yusuke; Makishima, Makoto; Matsumoto, Yotaro; Masumoto, Yui; Muranaka, Atsuya; Uchiyama, Masanobu; Hashimoto, Yuichi; Ishikawa, Minoru
• Is Part Of: Organic & biomolecular chemistry. Volume 19:Issue 2(2020)
• Page Start: 446
• Page End: 456
• Publication Date: 2020-12-17
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d0ob02083d
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : We found a novel molecular design for improvement in the aqueous solubility of small molecule drugs. 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.