Diarylquinolines, synthesis pathways and quantitative structure--activity relationship studies leading to the discovery of TMC207.

Janssen-Cilag France, Campus de Maigremont, BP615, 27106, Val de Reuil Cedex, France.
Future medicinal chemistry (Impact Factor: 3.31). 09/2011; 3(11):1345-60. DOI: 10.4155/fmc.11.79
Source: PubMed

ABSTRACT 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 structure-activity relationships of the diarylquinoline series on Mycobacterium smegmatis activity.