Phosphine boranes as less hydrophobic building blocks than alkanes and silanes: Structure-property relationship and estrogen-receptor-modulating potency of 4-phosphinophenol derivatives |
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| Institution: | 1. Institute for Quantitative Biosciences, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan;2. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan;1. School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China;2. Department of Medicinal, The Second Clinical Medical College of Northwest Minzu University & The Second Provincial People’s Hospital of Gansu Province, Lanzhou 730000, PR China;1. Department of Chemistry, Centre for Advanced Studies, Guru Nanak Dev University, Amritsar 143005, India;2. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India;1. Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China;2. Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, PR China;1. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China;2. Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;1. School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400 USA;2. School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332-0400 USA;3. Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0400 USA;4. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0400 USA;1. Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China;2. School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China;3. Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai 201203, PR China |
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| 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. |
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| Keywords: | Phosphorus Phosphine Phosphine borane Hydrophobicity Estrogen receptor |
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