Medicinal chemistry of quinolines as emerging anti-inflammatory agents: an overview

Quinoline-based small molecules have been explored and being developed as anti-inflammatory agents targeting several pharmacological targets namely Phosphodiesterase 4 (PDE4), Transient Receptor Potential Vanilloid 1 (TRPV1), TNF-α converting enzyme (TACE) and Cyclooxygenase (COX). Efforts on Structure Activity Relationship (SAR) studies revealed that the pharmacological activities and target specificities of these quinoline derivatives were mainly dependent on the nature and position of substituent(s) present on the quinoline ring. For example, quinolines having carboxamide moiety displayed TRPV1 antagonism whereas that with carboxylic acid showed COX-inhibition. Similarly, quinolines possessing aniline moiety at C-4, aryl group at C-8 and oxazole ring at C-5 showed PDE4 inhibition. These quinoline derivatives were synthesized by using various synthetic approaches like Pd-mediated C-C (e.g. Suzuki, Sonogashira type coupling etc.) or C-N (the Buchwald-Hartwig type coupling) or C-S bond formation, AlCl₃ induced C-C bond formation, traditional amide bond formation or amination, formation of ether linkage or additional heterocyclic rings. All these efforts resulted in the discovery of several quinoline-based anti-inflammatory agents for the potential treatment of acute as well as chronic inflammatory diseases.