Solid-phase synthesis of potential protein tyrosine phosphatase inhibitors via the Ugi four-component condensation.
A library of 108 alpha,alpha-difluoromethylenephosphonic acids was prepared by Ugi four-component condensation using Rink-NH2 resin, 4-[(diethoxyphosphinyl) difluoromethyl]benzoic acid, and a set of 18 aldehydes and 6 isonitriles. Following resin cleavage, the diethylphosphonate esters were hydrolyzed with trimethylsilyl bromide to yield the free acids which were assayed for inhibition of PTP alpha, PTP beta and PTP epsilon.
Li
Z
Z
Institute of Molecular and Cell Biology, National University of Singapore.
Yeo
S L
SL
Pallen
C J
CJ
Ganesan
A
A
D000447:Aldehydes; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D007463:Iodobenzoates; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009570:Nitriles; D063065:Organophosphonates / Q000737:chemistry; D011487:Protein Conformation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*
D000447:Aldehydes; D004791:Enzyme Inhibitors; D007463:Iodobenzoates; D009570:Nitriles; D063065:Organophosphonates; D017027:Protein Tyrosine Phosphatases