Indolecarboxamides are potent but poorly soluble mycobactericidal agents. Here we found that modifying the incipient scaffold by amide-amine substitution and replacing the indole ring with benzothiophene or benzoselenophene led to striking (10-20-fold) improvements in solubility. Potent activity could be achieved without the carboxamide linker but not in the absence of the indole ring. The indolylmethylamine, <i>N</i>-cyclooctyl-6-trifluoromethylindol-2-ylmethylamine (<b>33</b>, MIC<sub>90<i>Mtb</i></sub> 0.13 μM, MBC<sub>99.9<i>Mtb</i></sub> 0.63 μM), exemplifies a promising member that is more soluble and equipotent to its carboxamide equivalent. It is also an inhibitor of the mycolate transporter MmpL3, a property shared by the methylamines of benzothiophene and benzoselenophene.