Synthesis, structure elucidation and chemotherapeutic activity of 6‐substituted 1‐ethyl‐1,4‐dihydro‐7‐[(1‐imidazolyl)phenylmethyl]‐ 4‐oxo‐3‐quinolinecarboxylic acids

Abstract

The synthesis, structure elucidation and chemotherapeutic activity of novel 3‐quinolinecarboxylic acid derivatives are reported. These derivatives are characterized by a group (1‐imidazolyl)phenylmethyl attached to the 7‐position and chloro 10a, fluoro 10b or methoxy 10c appended to the 6‐position.

7-Azetidinylquinolones as Antibacterial Agents. 2. Synthesis and Biological Activity of 7-(2,3-Disubstituted-1-azetidinyl)-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic Acids. Properties and Structure-Activity Relationships of Quinolones with an Azetidine Moiety

“…2,2-Dimethyl-l-(diphenylmethyl)-3-azetidone (15). To a stirred solution of 13 (21.7 g, 0.081 mol) in acetic acid saturated with HC1 (75 mL) was added dropwise bromine (13.01 g, 0.082 mol), and then the solution was stirred for 4 h at room temperature.…”

“…The synthesis of 2,2-dimethyl-l-(diphenylmethyl)azetidin-3-ol lOe was not possible following the procedure mentioned above, because of the instability of the epoxide 9e at room temperature. The synthesis was carried out (Scheme 2) by bromination of the 3-methylbutanone tertiary carbon and substitution by benzhydrylamine to obtain 13, followed by bromination of the -methyl and cyclization in basic medium to afford 15. The final step was achieved by reduction of ketone 15 with NaBH4 in good yield.…”

“…These investigations led to a series of compounds substituted at the 7-position with azoles such as pyrrole (irloxacin13), or 4-methylimidazole ( 3,5-dimethyl-1 -piperazinyl 434514) and a series of (imidazolyl)phenylmethyl substituents attached to the 7-position via a carbon-carbon bond. 15 More recently, we have invested considerable effort into those C-7 groups bearing a 3-monosubstitutedand 3,3-disubstituted azetidine.1 This latter series showed broad-spectrum activity, particularly against Gram-positive organisms, improved in vivo efficacy, and high blood levels in the mouse. 8-Chloro-1-cyclopropylquinolones 5a-b, l-(2,4-difluorophenyl)naphthyridine 5c, and 8-chloro-l-(2,4-difluorophenyl)quinolones 5d and 6a exhibited the best overall microbiological profile.…”