Synthesis of novel 5-fluoro analogs of norfloxacin and ciprofloxacin

Abstract

A series of polyfluoro-3-quinolonecarboxylic acids have been synthesized and their in vitro antibacterial activity evaluated. The desired 7-(substituted amino) derivatives were prepared from the 5,6,7,8-tetrafluoroquinolone acids. Conversely, amine displacement occurred primarily at the 5-position when the ester was used. Structure-activity studies indicated that the antibacterial activity was greatest when the N-1 substituent was cyclopropyl and the 7-substituent was 4-methyl-1-piperazinyl. All 5-(substituted amino) derivatives showed poor in vitro activity.

Quinolone Compounds with Activity Against Multidrug-Resistant Gram-Positive Microorganisms

“…In position 5 of the quinolones various groups were introduced, such as nitro (Domagala et al 1988) unsubstituted or substituted amino [27,16,36] [17], alkyl [23,25], halogen [35,36], mercapto [35,36], hydroxy [36,17], alkoxy or tioalcooxi [35,36] In the series of 1-cyclopropyl-7-piperazinyl quinolones, the influence of the substituent in position 5 on the antimicrobial activity is manifested as follows:…”

Synthesis of norfloxacin analogues catalyzed by Lewis and Brönsted acids: An alternative pathway

“…Introduction of a heterocyclic amine (Table 3), classified as a poor nucleophile such as 5-amino-uracil into a fluoroquinolone ring by S N Ar reaction, was performed at room temperature in 24 h of reaction time and a 69% yield. [27], c-C 3 H 5 [29a] or excess of pyrrolidine/pyridine, 95 8C, 4 h for R 1 = C 2 H 5 [28].…”

Fluorine-containing 2,4-dioxo acids in the synthesis of heterocyclic compounds

“…Ethyl pentafluorobenzoylpyruvate (1e), like other b-DCC, 11,12,23,24,67 readily reacts with ethyl orthoformate to form ethyl 3-ethoxymethylidene-2,4-dioxo-4-pentafluorophenylbutyrate (24). The reactions of compound 24 with amines followed by cyclisation of the resulting ethyl 3- The active methylene group in compounds containing a b-dicarbonyl fragment is the reaction site for azocoupling with aryldiazonium salts to form the corresponding arylhydrazones.…”