title: Diarylquinolines, synthesis pathways and quantitative structure--activity relationship studies leading to the discovery of TMC207.
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.
authors: Janssen-Cilag France, Campus de Maigremont, BP615, 27106, Val de Reuil Cedex, France. jguillem@its.jnj.com
authors: Jerome
authors: J
authors: Guillemont
authors: Christophe
authors: C
authors: Meyer
authors: Alain
authors: A
authors: Poncelet
authors: Xavier
authors: X
authors: Bourdrez
authors: Koen
authors: K
authors: Andries
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D064687:Diarylquinolines; D055808:Drug Discovery / Q000379:methods*; D024901:Drug Resistance, Multiple, Bacterial; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000254:growth & development; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D011804:Quinolines; C493870:bedaquiline