Fig. 25

Key stages in the hit to lead pathway of OZ439. Initial replacement of the amide linker with a phenyl ether linker resulted in improved exposure while maintaining potency (O2). The exposure was further improved by changing the alkylamine chain to a piperazine ring (O3). Final replacement of the piperazine ring with a morpholine unit led to the optimized compound OZ439, which possessed better curative efficacy in vivo