Synthesis and biological evaluation of alpha,alpha-difluorobenzylphosphonic acid derivatives as small molecular inhibitors of protein-tyrosine phosphatase 1B.
A series of alpha,alpha-difluorobenzylphosphonic acids having a hydrophobic functional group were prepared via the Stille coupling reaction from halogenated alpha,alpha-difluorobenzylphosphonates. Evaluation of inhibitory activity toward protein tyrosine phosphatase (PTP 1B) revealed that the ethynyl, phenylethynyl and (E)-styryl groups on the benzene nuclei increased the inhibitory activity of alpha,alpha-difluorobenzylphosphonic acid. Inhibitory activities significantly increased upon introducing both (E)-styryl and bis-methylsulfonamide functional groups onto the benzene nuclei of alpha,alpha-difluorobenzylphosphonic acid.
Yokomatsu
T
T
School of Pharmacy, Tokyo University of Pharmacy & Life Science, Horinouchi, Hachioji, Japan.
Murano
T
T
Umesue
I
I
Soeda
S
S
Shimeno
H
H
Shibuya
S
S
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D063065:Organophosphonates; D017027:Protein Tyrosine Phosphatases