N-Aroyl-3,5-bis(benzylidene)-4-piperidones: a novel class of antimycobacterial agents.

A number of 3,5-bis(benzylidene)-4-piperidones 1 and some N-4-(2-aminoethoxy)phenylcarbonyl analogs 3-6 display excellent in vitro antimycobacterial properties. In particular, 1c and 6d are potent antimycobacterials which are well tolerated in mice and are identified as important lead molecules. The nature of both the benzylidene aryl rings and the terminal basic groups which affect the antimycobacterial potencies and the absence of neurotoxic side effects were identified. Several representative compounds stimulated respiration in mitochondria isolated from rat liver and this effect was not caused by the swelling of these organelles. Various guidelines for the creation of further related novel antimycobacterial agents are provided.