4-Hydroxy-2-quinolones. 108. N-R-amides of 9-fluoro-1-hydroxy-5-methyl-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid and their antitubercular activity

Abstract

from which alkyl-, dialkylaminoalkyl-, and hetarylamides as well as hydrazides were prepared. The structure and antitubercular properties of the compounds synthesized are discussed.Keywords: heterocyclic tricarbonylmethanes, 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid esters and amides, antitubercular activity, X-ray structural analysis.Fluoroquinolone preparations occupy an important place in the contemporary arsenal of antibacterial chemotherapeutic agents and amongst these C (8) /N (1) annelated tricyclic derivatives of the general structure 1 can be mentioned. They are noted for their high activity and good pharmacokinetic properties [2, 3]. Up to recent times it was considered that the modification of the carboxyl group of fluoroquinolones leads to a marked lowering of antimicrobial activity and carboxy derivatives can be active only in examples where they are readily converted to the starting acids in vivo. However, this claim has gradually been disproved by many investigations. As a result there have appeared the so called "double action" antibiotics which are esters of1a-e 1 a X = CH 2 , R = H (flumequine); b X = CH 2 , R = imidazol-1-yl (S-25932); c X = CH 2 , R = 4-methylpiperazin-1-yl (vebufloxacin); d X = O, R = 4-methylpiperazin-1-yl (ofloxacin); e X = S, R = 4-methylpiperazin-1-yl (rufloxacin)

Identification of Human Toll-like Receptor 2-Agonistic Activity in Dihydropyridine–Quinolone Carboxamides

“…The tricyclic dihydropyridine-quinolone core was synthesized using an elegant one-pot method developed by Ukrainets et al , A concerted nucleophilic addition–cyclization reaction of 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline with triethylmethanetricarboxylate afforded the ester 1 , which was subsequently displaced with a variety of amines to yield analogues 2 (hit compound) through 57 (Scheme ). We began our SAR exploration by evaluating substituted pyridines (analogues 3 – 21 ), an examination of which initially appeared to suggest that substituents at C2 and C6 of the pyridine ring were poorly tolerated, whereas those at C4 and C5 were well tolerated.…”