Raichurkar and coworkers also from AstraZeneca® (AstraZeneca R&D, Bangalore, India) have reported the discovery of pyrazolopyridones derivatives as promising antitubercular compounds . Initially, they investigated the antituberculosis activity of these compounds against a panel of sensitive and clinical isolated single drug-resistant strains. Compound (15) (Figure 5) presented MIC90 values ranging from 1.6–3.1 μM and low cytotoxicity against the human A549 cell line (IC50 160 μM). The authors also demonstrated through biochemical screening and genetic mapping that the target of compound (15) is decaprenylphosphoryl-β-D-ribose-2′-epimerase (DprE1), an enzyme that plays an important role in the biosynthesis of components of the mycobacterial cell wall . In vitro drug metabolism and pharmacokinetics properties were performed for this compound, that exhibits distribution coefficient (logD) of 3.9 and suboptimal aqueous solubility (1 μM), free plasma protein binding (1%), and clearance (27 μL/min/kg) . In another work, the synthesis and antituberculosis activity of pyrazolo[1,5-a]pyridine-3-carboxamide derivatives were reported. Specifically, compound (16) (Figure 5) has shown potent in vitro potency at nanomolar concentration, for which MIC90 values ranged from 11.1 to 223 nM against several clinically isolated MDR-TB strains. In addition, they evaluated the in vivo efficacy of compound (16) in a mouse model infected with the selectable marker-free autoluminescent Mtb H37Ra, a non-virulent strain. They observed a bactericidal activity of this compound, resulting in a reduction of bacterial burden using a modified real-time monitoring noninvasive bioluminescence assay .