Central pharmacological properties of 38 aminophosphonic acids and their derivatives, mostly newly synthesized, were investigated on mice and rats. Acute toxicity, neurotoxic activity, influence on spontaneous locomotor activity, body temperature, electrogenic and pentetrazol convulsions, on cerebral GABA level were tested. The most active compounds were (in a decreasing order of activity): 2-amino-7-phosphonoheptanoic, 2-amino-5-phosphonovaleric, 2-amino-8-phosphonooctanoic, 2-amino-2-methyl-3-methylphosphonopropionic, and 3-amino-3-hydroxy-5-phosphonovaleric acid.
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Eur J Med Chem
February 2025
Adam Mickiewicz University, Faculty of Chemistry, Uniwersytetu Poznańskiego 8, 61-614, Poznań, Poland. Electronic address:
Phosphonate analogues of α-amino acids are increasingly valued for their significant potential in medicinal chemistry. Fluorine is a "magic" element that plays a huge role in modulating the properties of organic compounds. In this work, we combined the two pharmacophores in the synthesis of three series of new α-aminophosphonates.
View Article and Find Full Text PDFChemMedChem
November 2024
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111, Budapest, Műegyetem rkp. 3., Hungary.
Phosphorus containing small molecules (particularly α-aminophosphonates, α-hydroxyphosphonates and bisphosphonates) represent a unique chemical space among the biologically active compounds. We selected 35 diverse compounds that showed remarkable cytotoxicity effects on various cancer cell lines. However, the exact mechanism of action often requires further investigations, in vitro or in silico target identification even though many target-based activity data were gathered for the above cluster of compounds.
View Article and Find Full Text PDFJ Am Chem Soc
May 2024
Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, Department of Chemistry, School of Science and Research Center for Industries of the Future, Westlake University, Hangzhou 310030, China.
α-Aminophosphonic acids as an important class of bioisosteres of α-amino acids demonstrate various biologically important activities. We report here the development of a highly enantioselective isomerization of α-iminophosphonates enabled by an extraordinarily efficient organocatalyst. This organocatalyst afforded a total turnover number (TON) of 20,000-1,000,000 for a wide range of α-alkyl iminophosphonates.
View Article and Find Full Text PDFOrg Biomol Chem
August 2023
Department of Physical and Quantum Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, ul. Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
α-Amido sulphones have been used as useful starting materials in the preparation of -chiral α-aminophosphonates and α-aminophosphonic acids. The developed methodology is based on a one-pot, base-catalysed generation of an imine intermediate followed by addition of a phosphorus nucleophile. The presented protocol is simple and effective and can be applied to a variety of structurally diverse α-amido sulphones and phosphorus nucleophiles, leading to the desired pure products after simple crystallization in very good yields.
View Article and Find Full Text PDFChemistry
December 2023
Institute of Organic Chemistry, Faculty of Chemistry, University of Vienna, Währingerstraße 38, 1090, Vienna, Austria.
α-Aminophosphonic acids have a remarkably broad bioactivity spectrum. They can function as highly efficient transition state mimics for a variety of hydrolytic and angiotensin-converting enzymes, which makes them interesting target structures for synthetic chemists. In particular, the phosphonic acid analogs to α-aminocarboxylic acids (P AAs) are potent enzyme inhibitors, but many of them are only available by chiral or enzymatic resolution; sometimes only one enantiomer is accessible, and several have never been prepared in enantiopure form at all.
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