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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:29

Article

Asquith, Christopher R. M.^1,2  Fleck, Neil³  Torrice, Chad D.⁴  Crona, Daniel J.^4,5  Grundner, Christoph^3,6  Zuercher, William J.^2,5 

[1] Univ North Carolina Chapel Hill, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA

[2] Univ North Carolina Chapel Hill, UNC Eshelman Sch Pharm, Struct Genom Consortium, Chapel Hill, NC 27599 USA

[3] Seattle Childrens Res Inst, Seattle, WA 98109 USA

[4] Univ North Carolina Chapel Hill, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27599 USA

[5] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[6] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA

关键词: Anti-tubercular;    4-Anilinoquinoline;    4-Anilinoquinazoline;    Mycobacterium tuberculosis (Mtb);   

DOI  :  10.1016/j.bmcl.2019.07.012

来源: Elsevier

【 摘 要 】

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 MIC90 value of 0.63-1.25 mu M. 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.

【 授权许可】

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