Discovery of new chemical entities as potential leads against Mycobacterium tuberculosis.

Abstract A series of biheterocyclic (1H-indole, benzofuran, pyrazolo[1,5- a ]pyrimidine, pyrazolo[1,5- a ]pyrimidin-5(4H)-one, imidazo[2,1- b ]thiazole and pyrazolo[5,1- b ]thiazole) derivatives were synthesized and evaluated for their anti-tubercular activities. The imidazo[2,1- b ]thiazoles 9a – c and pyrazolo[5,1 -b ]thiazoles 10a – c exhibited promising anti-tubercular activity in varying degrees. Especially, the 2,6-dimethylpyrazolo[5,1- b ]thiazole 10a exhibited strong suppressing function against H37Ra strain with MIC value of 0.03 μg/mL. Compound 10a also displayed good pharmacokinetic profiles with oral bioavailability ( F ) of 41.7% and a half-life of 13.4 h. Furthermore, 10a significantly reduced the bacterial burden in an autoluminescent H37Ra infected mouse model, suggesting its promising potential for development of anti-tubercular drugs.