Benzothiozinone derivatives with anti-tubercular Activity−Further side chain investigation

A series of novel benzothiozinone (BTZ) derivatives were designed, prepared and evaluated for antituberculosis activity. Specifically, the BTZ pharmacophore is retained and the previous heterocyclic ring linker is replaced by alkynyl or vinyl linker, the resulting compounds displayed about 5−fold improved antimycobacterial activity. We further revealed that the linker attached tail group affects the compound metabolic stability, potency and other drug like properties. This work led to the discovery of two compounds (A1 and A11) with acceptable low MICs and improved metabolic stability. The representative compound A11 demonstrated bactericidal efficacy in an acute TB infection mouse model.