Aryl Sulfonamides as a New Antitubercular Series: Discovery, Optimization and Target Identification ^†

Tuberculosis (TB) remains a major global health problem. An estimated one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. In 2015, 1.8 million people died from the disease. The development of new anti-TB therapeutics is urgently needed due to the emergence of multi-drug resistant strains (MDR and XDR-TB) as well as the co-infection with other pathogens (e.g., VIH).

World Health Organization (http://www.who.int/tb/publications/global_report/en/).

A Whole Cell HTS with GSK´s two million compound collection using Mycobacterium bovis BCG as a surrogate of Mycobacterium tuberculosis and subsequent confirmation of the obtained hits in Mtb was performed. As a result, several families with interesting antitubercular features were identified. An aryl sulfonamide series presenting a particularly promising profile was prioritized for optimization.

Details of the phenotypic screen, the initial Hit profile, preliminary SAR, Medicinal Chemistry activities and identification of the biological target will be presented.