BTZ043

BTZ043 is a DprE1 inhibitor with nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. (In Vitro) :The MIC of BTZ043 against M. tuberculosis H37Rv and Mycobacterium smegmatis are 1 ng/mL (2.3 nM) and 4 ng/mL (9.2 nM), respectively. The in vitro activity of BTZ043 against 30 Nocardia brasiliensis isolates is also tested. The MIC50 and MIC90 values for BTZ043 are 0.125 and 0.25 μg/mL. The MIC for N. carnea ATCC 6847 is 0.003μg/mL, for N. transvalensis ATCC 6865 is 0.003μg/mL, for N. brasiliensis NCTC10300 is 0.03 μg/mL, and for N. brasiliensis HUJEG-1 is 0.125μg/mL. The MIC value for M. tuberculosis H37Rv is 0.000976 μg/mL. The MIC value of BTZ-043 is >64 μg/mL for Escherichia coli ATCC 25922 and S. aureus ATCC 29213. (In Vivo) :Four weeks of treatment with BTZ043 reduces the bacterial burden in the lungs and spleens by 1 and 2 logs, respectively, at the concentrations used. Additional results suggest that BTZ043 efficacy is time-rather than dose-dependent. Acute (5 g/kg) and chronic (25 and 250 mg/kg) toxicology studies in uninfected mice show that, even at the highest dose tested, there are no adverse anatomical, behavioral, or physiological effects after one month.

1161233-85-7

>98% (HPLC)

DMSO : 13.3 mg/mL 30.83 mM

C[C@H]1COC2 (O1) CCN (CC2) c1nc (=O) c2cc (cc (c2s1) [N+] (=O) [O-]) C (F) (F) F

C17H16F3N3O5S

431.39

Storage temperature: -20°C. Stability: ≥ 2 years