Abstract: | 3,5‐Bis(arylidene)‐4‐piperidone (BAP) derivatives display good antitumour and anti‐inflammatory activities because of their double α,β‐unsaturated ketone structural characteristics. If N‐benzenesulfonyl substituents are introduced into BAPs, the configuration of the BAPs would change significantly and their anti‐inflammatory activities should improve. Four N‐benzenesulfonyl BAPs, namely (3E,5E)‐1‐(4‐methylbenzenesulfonyl)‐3,5‐bis4‐(trifluoromethyl)benzylidene]piperidin‐4‐one dichloromethane monosolvate, C28H21F6NO3S·CH2Cl2, ( 4 ), (3E,5E)‐1‐(4‐fluorobenzenesulfonyl)‐3,5‐bis4‐(trifluoromethyl)benzylidene]piperidin‐4‐one, C27H18F7NO3S, ( 5 ), (3E,5E)‐1‐(4‐nitrobenzenesulfonyl)‐3,5‐bis4‐(trifluoromethyl)benzylidene]piperidin‐4‐one, C27H18F6N2O5S, ( 6 ), and (3E,5E)‐1‐(4‐cyanobenzenesulfonyl)‐3,5‐bis4‐(trifluoromethyl)benzylidene]piperidin‐4‐one dichloromethane monosolvate, C28H18F6N2O3S·CH2Cl2, ( 7 ), were prepared by Claisen–Schmidt condensation and N‐sulfonylation. They were characterized by NMR, FT–IR and HRMS (high resolution mass spectrometry). Single‐crystal structure analysis reveals that the two 4‐(trifluoromethyl)phenyl rings on both sides of the piperidone ring in ( 4 )–( 7 ) adopt an E stereochemistry of the olefinic double bonds. Molecules of both ( 4 ) and ( 6 ) are connected by hydrogen bonds into one‐dimensional chains. In ( 5 ) and ( 7 ), pairs of adjacent molecules embrace through intermolecular hydrogen bonds to form a bimolecular combination, which are further extended into a two‐dimensional sheet. The anti‐inflammatory activity data reveal that ( 4 )–( 7 ) significantly inhibit LPS‐induced interleukin (IL‐6) and tumour necrosis factor (TNF‐α) secretion. Most importantly, ( 6 ) and ( 7 ), with strong electron‐withdrawing substituents, display more potential inhibitory effects than ( 4 ) and ( 5 ). |