Synthesis of [difluoro-(3-alkenylphenyl)-methyl]-phosphonic acids on non-crosslinked polystyrene and their evaluation as inhibitors of PTP1B.
A series of [difluoro-(3-alkenylphenyl)-methyl]-phosphonates were prepared on non-crosslinked polystyrene, a soluble polymer support. After cleavage from the support, the resulting phosphonic acids were examined for inhibition with protein tyrosine phosphatase 1B. Compound 20, bearing an alpha,beta-unsaturated allyl ester moiety, was the most potent of this series of compounds, being a reversible, competitive inhibitor with a K(i) of 8.0+/-1.4 microM.
Hum
Gabriel
G
Department of Chemistry, University of Waterloo, Ontario, Canada.
Lee
Jason
J
Taylor
Scott D
SD
D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004952:Esters / Q000737:chemistry; D020128:Inhibitory Concentration 50; D063065:Organophosphonates / Q000737:chemistry* / Q000494:pharmacology*; D011137:Polystyrenes / Q000737:chemistry*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D004952:Esters; D063065:Organophosphonates; D011137:Polystyrenes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases