Over the last decades, massive misuse of antibiotics prompted the apparition of resistances in many microorganisms such as ESKAPEE pathogens responsible for various nosocomial infections. 1 Indeed, the selective pressure put on sensitive bacteria by conventional antimicrobial molecules that cause their death promotes resistant strain survival. The development of antivirulence agents that could attenuate bacteria pathogenicity without affecting their growth, seems to be a new promising

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... c strategy. This could facilitate the host's defence by immune system and restore the associated efficiency of conventional treatments (Fig. 1) . 2 The inhibition of quorum sensing (QS) that refers to bacterial communication systems, could disrupt, especially in P. aeruginosa, virulence pathways (pyocyanin or rhamnolipid production) and intra/inter-species protective interactions (biofilm formation). Among a pool of promising pharmacological targets provided by QS, the interest of Pseudomonas Quinolone Signal receptor (PqsR) that regulates virulence gene expression in response to environmental factors and population density once activated by its natural ligand (PQS), has emerged for the development of inhibitors. 3 Synthesis The design of new 2-heteroaryl-4-quinolones relies on pallado-catalyzed cross-coupling reactions between different 2-bromo-4-chloroquinoline precursors 1 and various second heteroaryl derivatives (Fig. 3) such as: • 4, 5 or 6-heteroarylboronic esters 2a-c in the series I (Suzuki C-C couplings, Table 1 ), • or N-heteroarylpiperazine derivatives 5 in the series II (Buchwald-Hartwig C-N couplings).