Meta -Non-flat substituents: A novel molecular design to improve aqueous solubility in small molecule drug discovery

Yuki Ichikawa, Michiaki Hiramatsu, Yusuke Mita, Makoto Makishima, Yotaro Matsumoto, Yui Masumoto, Atsuya Muranaka, Masanobu Uchiyama, Yuichi Hashimoto, Minoru Ishikawa

Research output: Contribution to journalArticlepeer-review

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. This journal is

Original languageEnglish
Pages (from-to)446-456
Number of pages11
JournalOrganic and Biomolecular Chemistry
Volume19
Issue number2
DOIs
Publication statusPublished - 2021 Jan 14

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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