Anti-tubercular activity of novel 4-anilinoquinolines and 4-anilinoquinazolines
| Autor: | Christopher R. M. Asquith, Christoph Grundner, William J. Zuercher, Chad Torrice, Neil Fleck, Daniel J. Crona |
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| Rok vydání: | 2019 |
| Předmět: |
Clinical Biochemistry
Antitubercular Agents Pharmaceutical Science Microbial Sensitivity Tests 01 natural sciences Biochemistry Article Mycobacterium tuberculosis Structure-Activity Relationship chemistry.chemical_compound Aniline Drug Discovery Quinazoline Potency Anti tubercular Molecular Biology Aniline Compounds Dose-Response Relationship Drug Molecular Structure biology 010405 organic chemistry Organic Chemistry Quinoline biology.organism_classification Combinatorial chemistry 0104 chemical sciences 3. Good health 010404 medicinal & biomolecular chemistry chemistry Quinazolines Quinolines Molecular Medicine |
| Zdroj: | Bioorg Med Chem Lett |
| ISSN: | 0960-894X |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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