Figure 1.
Chemical structures of compounds 1–25.
Table 1.
In vitro antimycobacterial activity against M. tuberculosis H37Rv, activity against M. tuberculosis H37Rv in the LORA, cytotoxicity in Vero cells and HepG2 cells, of compounds 1–4.
Table 2.
CHILogD, % HSA binding, % PPB, clearance in mouse microsomes of compounds 1–4.
Table 3.
Chemical structure, in vitro antimycobacterial activity against M. tuberculosis H37Rv, activity against M. tuberculosis H37Rv in the LORA, and cytotoxicity in Vero cells and HepG2 cells of compounds 5–25.
Table 4.
Clearance in mouse and human microsomes of compounds 5–25.
Table 5.
CHILogD, % HSA binding and % PPB of compounds 5–25.
Figure 2.
Peripheral blood levels of compound 9 after oral administration to C57BL/6 mice (n = 3) at 50 mg/kg, as a suspension in 1% methyl cellulose; Tlast = 24 h.
Figure 3.
Acute infection model dose-response curve correlating logCFU count reduction in the lungs of mice with different doses of rifampicin, isoniazid, moxifloxacin, and compound 9.
Table 6.
A direct comparison in terms of the Areas Under the Curve (AUC) and oral doses associated with a 99% reduction of cfu counts in the lungs of infected mice (ED99) compared to untreated control for rifampicin, isoniazid, moxifloxacin and compound 9.
Table 7.
MIC (µM) of compounds 1, 5, and 8 and amino acid substitutions in the mmpL3 genes of M. tuberculosis H37Rv and M. bovis BCG mutants isolated as resistant to compound 5 (DR4-DR9) and 8 (DR1-DR3, M1 and M8).