@article{20acd87d22b04d95802965e2d97d8ea1,
title = "Meta -Non-flat substituents: A novel molecular design to improve aqueous solubility in small molecule drug discovery",
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 ",
author = "Yuki Ichikawa and Michiaki Hiramatsu and Yusuke Mita and Makoto Makishima and Yotaro Matsumoto and Yui Masumoto and Atsuya Muranaka and Masanobu Uchiyama and Yuichi Hashimoto and Minoru Ishikawa",
note = "Funding Information: The work described in this paper was partially supported by the Grants-in Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Japan Society for the Promotion of Science, Platform for Drug Discovery, Informatics, and Structural Life Science, and The Tokyo Biochemical Research Foundation (KAKENHI Grant No. 17H03996 (Y. H.), no. 17H06173 (M. U.), and no. 25293027 (M. I.)). The authors thank Dr Daisuke Hashizume of RIKEN for the X-ray crystallographic analysis. The DSC measurements were performed at Meiji Seika Pharma Co., Ltd. Publisher Copyright: {\textcopyright} The Royal Society of Chemistry.",
year = "2021",
month = jan,
day = "14",
doi = "10.1039/d0ob02083d",
language = "English",
volume = "19",
pages = "446--456",
journal = "Organic and Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
number = "2",
}