Diarylquinolines

Diarylquinolines are a class of heterocyclic compounds built on a quinoline core bearing two aryl substituents. The aryl groups may be located at different positions on the ring system, giving a variety of diarylated quinolines. The quinoline nitrogen provides basicity and participates in the compounds’ physicochemical properties, influencing lipophilicity, pKa, and the ability to cross membranes. This structural motif is pursued to achieve potent biological activity while maintaining selectivity in targeting microbial or other disease-relevant pathways.

The most prominent member is bedaquiline, a diarylquinoline approved for the treatment of multidrug-resistant tuberculosis. Bedaquiline exerts its antimycobacterial effect by inhibiting mycobacterial ATP synthase, collapsing energy production and leading to bacterial death. The diarylquinoline framework has also been studied in other derivatives with the aim of improving pharmacokinetic profiles, reducing toxicity, or expanding activity to other organisms.

Common routes to diarylquinolines combine construction of the quinoline nucleus with subsequent installation of aryl groups. Synthetic strategies include Friedländer-type condensations, annulation sequences, and modern cross-coupling methods such as Suzuki–Miyaura or other C–C bond-forming reactions to introduce the aryl substituents. Substituent patterns on the aryl rings and on the quinoline core modulate potency, selectivity, and solubility, with bulky hydrophobic groups often enhancing activity in antimicrobial applications.

Applications and significance: diarylquinolines are primarily explored as antimicrobial agents, particularly against Mycobacterium tuberculosis. Bedaquiline remains the leading example in clinical use, with ongoing research to identify additional diarylquinolines that retain activity while minimizing adverse effects such as cardiotoxicity. As with many lipophilic cationic compounds, careful pharmacovigilance and therapy management are emphasized in clinical settings.