TYRPHOSTINS .6. DIMERIC BENZYLIDENEMALONONITRILE TYRPHOSTINS - POTENTINHIBITORS OF EGF RECEPTOR TYROSINE KINASE IN-VITRO

Benzylidenemalononitrile (BMN) tyrphostins were previously found to be potent inhibitors of EGF receptor (EGFR) tyrosine kinase activity. Si nce these compounds were found to compete for the substrate and someti mes with the ATP site and since EGFR acts as a dimer, we prepared a se ries of dimeric tyrphostins. These dimeric tyrphostins were built from two BMN units linked by various spacers and designed to fit the dimer ic cross-autophosphorylation signal transduction intermediate of the E GFR tyrosine kinases. Structure-activity relationship of these potent dimeric EGF receptor tyrosine kinase inhibitors is reported.