Diarylquinolines, synthesis pathways and quantitative structure-activity relationship studies leading to the discovery of TMC207
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Future medicinal chemistry
, p. 1345-1360
University of Antwerp
The emergence of multidrug-resistant strains of Mycobacterium tuberculosis and resistance to current anti-TB drugs call for the discovery and development of new effective anti-TB drugs. TMC207 is the lead candidate of a novel class of antimycobacterial agents, the diarylquinolines, which specifically inhibit mycobacterial ATP synthase and displays high activity against both drug-susceptible and multidrug-resistant strains of Mycobacterium tuberculosis. This article covers both synthesis pathways as well as qualitative and quantitative analyses of the structureactivity relationships of the diarylquinoline series on Mycobacterium smegmatis activity.