Structure-activity relationship (SAR) studies of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione: development of potential substrate-specific ERK1/2 inhibitors.

A series of analogs of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione, a putative substrate-specific ERK1/2 inhibitor, were synthesized and biologically characterized in human leukemia U937 cells to define its pharmacophore. It was discovered that shift of ethoxy substitution from the 4- to the 2-position on the phenyl ring significantly improved functional activities of inhibiting cell proliferation and inducing apoptosis. This may provide access to a new lead for developing ERK1/2 substrate-specific inhibitors.