Solid-phase synthesis of potential protein tyrosine phosphatase inhibitors via the Ugi four-component condensation

A library of 108 α,α-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 PTPα, PTPβ and PTP .