(1), which projects towards the solvent exposed space, is oriented near Cys368. Analogs were therefore designed from the TCMDC-135051 (1) scaffold via a piperazine linker, a natural extension of the diethylamine, to orientate warheads towards the target residue (Fig. ). The isopropyl group from TCMDC-135051 (1) was omitted to reduce the molecular weight and lipophilicity, given this group was previously found to be non-essential for kinase inhibition. A series of analogs was designed featuring warheads of increasing reactivity (Fig. ).