Synthesis, crystal structures and anti‐inflammatory activity of four 3,5‐bis(arylidene)‐ N N ‐benzenesulfonyl‐4‐piperidone derivatives

摘要

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 (3 E ,5 E )‐1‐(4‐methylbenzenesulfonyl)‐3,5‐bis[4‐(trifluoromethyl)benzylidene]piperidin‐4‐one dichloromethane monosolvate, C 28 H 21 F 6 NO 3 S·CH 2 Cl 2 , ( 4 ), (3 E ,5 E )‐1‐(4‐fluorobenzenesulfonyl)‐3,5‐bis[4‐(trifluoromethyl)benzylidene]piperidin‐4‐one, C 27 H 18 F 7 NO 3 S, ( 5 ), (3 E ,5 E )‐1‐(4‐nitrobenzenesulfonyl)‐3,5‐bis[4‐(trifluoromethyl)benzylidene]piperidin‐4‐one, C 27 H 18 F 6 N 2 O 5 S, ( 6 ), and (3 E ,5 E )‐1‐(4‐cyanobenzenesulfonyl)‐3,5‐bis[4‐(trifluoromethyl)benzylidene]piperidin‐4‐one dichloromethane monosolvate, C 28 H 18 F 6 N 2 O 3 S·CH 2 Cl 2 , ( 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 ).