Synthesis and Antimycobacterial Activity of Various 1-(8-Quinolinyloxy)-3-piperazinyl(piperidinyl)-5- (4-cyano-3-trifluoromethylphenylamino)-s-triazines

This study presents the synthesis of novel 1-(8-quinolinyloxy)-3-piperazinyl(piperidinyl)-5-(4-cyano-3-trifluoromethylphenyl amino)-s-triazines. The synthetic route to final piperazinyl s-triazines consists of two nucleophilic substitution reactions of 4-amino-2-trifluoromethylbenzonitrile and 8-hydroxyquinoline with 2,4,6-trichloro-1,3,5-triazine resulting in 2,4-disubstituted-6-chloro-1,3,5-triazine derivatives to introduce the piperazinyl or piperidinyl functionality. The structures of the compounds were elucidated with the aid of IR, 1H NMR, 19F NMR, mass spectroscopy and elemental analysis. The title compounds were then investigated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv strain by using BACTEC MGIT and Lowenstein–Jensen MIC method. Compound 4-[4- (3,5-dimethylpiperidin-1-yl)-6-(quinolin-8-yloxy)-1,3,5-triazin-2-ylamino]-2-trifluoromethylbenzonitrile (5n) was the most potent one among the tested compounds. It was as potent as ethambutol to inhibit M. tuberculosis H37Rv completely (99%) at the minimum inhibitory concentration (MIC) of 3.12 μg/mL. Compounds 5p, 5s and 5u have shown equal potency to that of pyrazinamide at the minimum inhibitory concentration (MIC) of 6.25 mg/mL to inhibit (99%) M. tuberculosis H37Rv.