Figure 1.

Strategy of bedaquiline simplification. Bedaquiline was split into the core quinoline moiety, three major and two minor fragments (bromo and hydroxy groups). The major fragments comprise the phenyl ring (fragment A), the side chain dimethylaminoethyl (fragment B), and the naphthylmethyl ring (fragment C). These major fragments were reattached to the core quinoline moiety to design four series of new analogues while gradually replacing the chiral linkage.