Design, Synthesis, and Evaluation of B-(Trifluoromethyl)phenyl Phosphine–Borane Derivatives as Novel Progesterone Receptor Antagonists
2024
Yu Miyajima | Kotaro Ochiai | Shinya Fujii
We previously revealed that phosphine&ndash:boranes can function as molecular frameworks for biofunctional molecules. In the present study, we exploited the diversity of available phosphines to design and synthesize a series of B-(trifluoromethyl)phenyl phosphine&ndash:borane derivatives as novel progesterone receptor (PR) antagonists. We revealed that the synthesized phosphine&ndash:borane derivatives exhibited LogP values in a predictable manner and that the P&ndash:H group in the phosphine&ndash:borane was almost nonpolar. Among the synthesized phosphine&ndash:boranes, which exhibited PR antagonistic activity, B-(4-trifluoromethyl)phenyl tricyclopropylphosphine&ndash:borane was the most potent with an IC50 value of 0.54 &mu:M. A docking simulation indicated that the tricyclopropylphosphine moiety plays an important role in ligand&ndash:receptor interactions. These results support the idea that phosphine&ndash:boranes are versatile structural options in drug discovery, and the developed compounds are promising lead compounds for further structural development of next-generation PR antagonists.
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