Kachkovskyi G. Synthesis and properties of phosphonic acids possessing isoindolin-1-one moiety

The phosphonic acids possessing isoindolin-1-one moiety. Development of methods of synthesis phosphonic the acids modified by a fragment isoindolin-1-one, studying of their properties, inhibitory activity concerning the some people фосфатаз. Chemical synthesis, a nuclear magnetic resonance spectroscopy, chromatomas-spectrometry, PMR research, computer modeling, biological researches in vitro. Convenient approach to the titled compounds was elaborated. It consists in dehydrative aromatization of (2,3,7,7а-tetrahydro-3а,6-epoxyisoindolin-1-one)phosphonates, which are the products of tandem acylation/[4+2]-cycloaddition reaction of furfurylamino-phosphonates with maleic anhydride. It was shown that dehydrative aromatization may be accompanied with dephosphorylation which proceeds with assistance of carboxyl group at the position 7 of isoindolin-1-one ring. Furthermore, phosphonoanalogues of bioactive isoindolinones were synthesized: phosphonoindoprofen and phosphonobenzo[c]pyroglutamic acid. Molecular docking calculations and assays showed that some of compounds synthesized inhibit NPP/PDE 1 and Yersinia PTP with IC50 values in the micromolar range. Sphere of use: bioorganic chemistry.