Design, Synthesis, and Evaluation of <i>B</i>-(Trifluoromethyl)phenyl Phosphine–Borane Derivatives as Novel Progesterone Receptor Antagonists
We previously revealed that phosphine–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 <i>B</i>-(trifluoromethyl)phenyl phosphine–borane derivatives as n...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/7/1587 |
| _version_ | 1797212218244202496 |
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| author | Yu Miyajima Kotaro Ochiai Shinya Fujii |
| author_facet | Yu Miyajima Kotaro Ochiai Shinya Fujii |
| author_sort | Yu Miyajima |
| collection | DOAJ |
| description | We previously revealed that phosphine–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 <i>B</i>-(trifluoromethyl)phenyl phosphine–borane derivatives as novel progesterone receptor (PR) antagonists. We revealed that the synthesized phosphine–borane derivatives exhibited Log<i>P</i> values in a predictable manner and that the P–H group in the phosphine–borane was almost nonpolar. Among the synthesized phosphine–boranes, which exhibited PR antagonistic activity, <i>B</i>-(4-trifluoromethyl)phenyl tricyclopropylphosphine–borane was the most potent with an IC<sub>50</sub> value of 0.54 μM. A docking simulation indicated that the tricyclopropylphosphine moiety plays an important role in ligand–receptor interactions. These results support the idea that phosphine–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. |
| first_indexed | 2024-04-24T10:38:53Z |
| format | Article |
| id | doaj.art-395aeb94626b4dcdb4a981e3e0150a94 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-24T10:38:53Z |
| publishDate | 2024-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-395aeb94626b4dcdb4a981e3e0150a942024-04-12T13:23:30ZengMDPI AGMolecules1420-30492024-04-01297158710.3390/molecules29071587Design, Synthesis, and Evaluation of <i>B</i>-(Trifluoromethyl)phenyl Phosphine–Borane Derivatives as Novel Progesterone Receptor AntagonistsYu Miyajima0Kotaro Ochiai1Shinya Fujii2Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, JapanInstitute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, JapanInstitute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, JapanWe previously revealed that phosphine–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 <i>B</i>-(trifluoromethyl)phenyl phosphine–borane derivatives as novel progesterone receptor (PR) antagonists. We revealed that the synthesized phosphine–borane derivatives exhibited Log<i>P</i> values in a predictable manner and that the P–H group in the phosphine–borane was almost nonpolar. Among the synthesized phosphine–boranes, which exhibited PR antagonistic activity, <i>B</i>-(4-trifluoromethyl)phenyl tricyclopropylphosphine–borane was the most potent with an IC<sub>50</sub> value of 0.54 μM. A docking simulation indicated that the tricyclopropylphosphine moiety plays an important role in ligand–receptor interactions. These results support the idea that phosphine–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.https://www.mdpi.com/1420-3049/29/7/1587phosphorusphosphine–boranehydrophobicityprogesterone receptorantagoniststructural optimization |
| spellingShingle | Yu Miyajima Kotaro Ochiai Shinya Fujii Design, Synthesis, and Evaluation of <i>B</i>-(Trifluoromethyl)phenyl Phosphine–Borane Derivatives as Novel Progesterone Receptor Antagonists Molecules phosphorus phosphine–borane hydrophobicity progesterone receptor antagonist structural optimization |
| title | Design, Synthesis, and Evaluation of <i>B</i>-(Trifluoromethyl)phenyl Phosphine–Borane Derivatives as Novel Progesterone Receptor Antagonists |
| title_full | Design, Synthesis, and Evaluation of <i>B</i>-(Trifluoromethyl)phenyl Phosphine–Borane Derivatives as Novel Progesterone Receptor Antagonists |
| title_fullStr | Design, Synthesis, and Evaluation of <i>B</i>-(Trifluoromethyl)phenyl Phosphine–Borane Derivatives as Novel Progesterone Receptor Antagonists |
| title_full_unstemmed | Design, Synthesis, and Evaluation of <i>B</i>-(Trifluoromethyl)phenyl Phosphine–Borane Derivatives as Novel Progesterone Receptor Antagonists |
| title_short | Design, Synthesis, and Evaluation of <i>B</i>-(Trifluoromethyl)phenyl Phosphine–Borane Derivatives as Novel Progesterone Receptor Antagonists |
| title_sort | design synthesis and evaluation of i b i trifluoromethyl phenyl phosphine borane derivatives as novel progesterone receptor antagonists |
| topic | phosphorus phosphine–borane hydrophobicity progesterone receptor antagonist structural optimization |
| url | https://www.mdpi.com/1420-3049/29/7/1587 |
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