The quorum sensing (QS) enhanced transcriptional regulator SdiA of S. typhimurium is the best known and potential target and responds to a broad range of AHLs and AHL analogs. On the other hand, in many gram-negative bacteria including S. typhimurium, brominated furanones were reported to have inhibitory activity against the QS phenotypes. Motivated by both, we designed an in silico group of halogenated AHLs by substituting halogen compounds (Br, Cl, F and I) on the lactone ring of AHLs and analyzed their interactions with SdiA. The best analogs based on their docking score and another 18 training sets with inhibitory activity against S. typhimurium QS were used to design the pharmacophore. This pharmacophore model was used as a 3D database query against the MayBridge Database consisting of 56,000 compounds and subsequently, the screened compounds were filtered by Lipinski’s rule and ADMET properties. This results in 10 compounds as probable leads to inhibit the SdiA activity and they were docked in the active site of SdiA. Among these, 3 compounds CD01374, RJF00047, and KM10117 exhibited the best docking scores and also favors the necessary hydrogen bond interactions with the essential amino acids in SdiA, and thus identified as novel leads to inhibit Salmonella pathogenicity.