The present manuscript reports on the identificationof a promisingarylsulfonamide of 2-phenylpyrrole-3-carboxamide analogue (27) which displays inverse agonist properties at 5-HT6R-operated Gs andCdk5 signaling pathways.We also examined whether 27 is distributed to the brainand could reverse cognitive impairments in the novel object recognition(NOR) test under scopolamine-induced memory decline conditions andwhether it could facilitate cognitive flexibility in the attentionalset-shifting task (ASST) in rats. This evidence concerns the gene HTR6 and Cognitive impairment.