Anti-tubercular activity of novel 4-anilinoquinolines and 4-anilinoquinazolines

ABSTRACT We screened a series of 4-anilinoquinolines and 4-anilinoquinazolines and identified novel inhibitors of Mycobacterium tuberculosis ( Mtb ). The focused 4-anilinoquinoline/quinazoline scaffold arrays yielded compounds with high potency and the identification of 6,7-dimethoxy- N -(4-((4-methylbenzyl)oxy)phenyl)quinolin-4-amine ( 34 ) with an MIC 90 value of 0.63-1.25 μM. We also defined a series of key structural features, including the benzyloxy aniline and the 6,7-dimethoxy quinoline ring, that are important for Mtb inhibition. Importantly the compounds showed very limited toxicity and scope for further improvement by iterative medicinal chemistry.