Phosphine boranes as less hydrophobic building blocks than alkanes and silanes: Structure-property relationship and estrogen-receptor-modulating potency of 4-phosphinophenol derivatives

  • Bioorg Med Chem. 2020 Feb 15;28(4):115310. doi: 10.1016/j.bmc.2020.115310.
Hiroki Saito  1 ,  Yuichiro Matsumoto  1 ,  Yuichi Hashimoto  1 ,  Shinya Fujii  2
Affiliations
  • 1. Institute for Quantitative Biosciences, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
  • 2. Institute for Quantitative Biosciences, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan; Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. Electronic address: [email protected].
PMID: 31980362 DOI: 10.1016/j.bmc.2020.115310
Abstract

Increasing structural options in medicinal chemistry is important for the development of novel and distinctive drug candidates. In this study, we focused on phosphorus-containing functionalities. We designed and synthesized a series of phosphinophenol derivatives and determined their physicochemical properties, including hydrophobicity parameter LogP, and their biological activity toward Estrogen receptor (ER). Notably, the phosphine borane derivatives (9 and 14) exhibited potent ER-antagonistic activity, exceeding the potency of the corresponding alkane (15) and silane (16) derivatives, despite having a less hydrophobic nature. The determined physicochemical parameters will be helpful for the rational design of phosphorus-containing biologically active compounds. Our results indicate that phosphine boranes are a promising new chemical entry in the range of structural options for drug discovery.

Keywords
Estrogen receptor; Hydrophobicity; Phosphine; Phosphine borane; Phosphorus.
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