Synthesis and Biological Evaluation of Difluoromethylenephosphonic Acid Derivatives

点击翻译按钮获取中文摘要

1.Synthesis and biological evaluation of novel nucleotide analogues possessing difluoromethylene phosphonic acids. Novel nucleotide analogues derived from connecting purine nucleobases and difluoromethylenephosphonic acid (CFィイD22ィエD2POィイD23ィエD2HィイD22ィエD2) with a variety of alkyl spacer were prepared for "multi-substrate analogue" inhibitors of purine nucleoside phosphorylase (PNPs). The cyclopropane and the tetrahydrofuran moieties of the alkyl spacer connecting a nucleobase and CFィイD22ィエD2POィイD23ィエD2HィイD22ィエD2 were found to be effective for good inhibition of PNPs.2.Synthesis of α, α-difluorobenzylphosphonic acid derivatives for inhibitors of purotein-tyrosine phosphatase 1B. A series of α, α-difluorobenzylphosphonic acids having a hydrophobic functional group were prepared via the Stille coupling reaction from halogenated α, α-difluorobenzylphosphonates. Evaluation of inhibitory activity toward protein tyrosine phosphatase (PTP 1B) revealed that the ethynyl, phenylthynyl and (E)-styryl groups on the benzene nuclei increased the inhibitory activity upon α, α-defluorobenzylphosphonic acid. Inhibitory activities significantly increased upon introducing both (E)-styryl and bis-methylsulfonamide functional groups onto the benzene nuclei of α, α-difluorobenzylphosphonic acid.