112811-57-1Relevant articles and documents
Synthesis and antimicrobial evaluation of novel N -substituted β-hydroxy benzimidazole sulfone fluoroquinolones by selective oxidation using ticl 4-H 2O 2
Guruswamy,Arul
, p. 1205 - 1213 (2013)
The synthesis of N-substituted β-hydroxy benzimidazole sulfones containing 8-methoxy fluoroquinolone has been described and they were evaluated for antimicrobial activities. The compounds of N-substituted β-hydroxy benzimidazole sulfides (4a-e) and N-substituted β-hydroxy benzimidazole sulfones (5a-e) at C-7 of fluoroquinoline exhibited superior activity in vitro. 8-Methoxy fluoroquinolone carboxylic acid (1), reaction with piperizine in acetonitrile in presence of triethylamine under reflux gives 7-piperazinyl-8-methoxyfluoroquinolone (2). The latter is reacted with epichlorohydrine in presence of NaOH in acetone yielded N-substituted epoxide (3), which on treatment with 5-substituted-2-mercaptobenzimidazoles gives N-substituted β-hydroxy benzimidazole sulfides (4). Further, 4 on treatment with TiCl4-H2O2 and in DCM yielded the corresponding N-substituted β-hydroxy benzimidazole sulfone (5).
Effect of N-1/C-8 ring fusion and C-7 ring structure on fluoroquinolone lethality
Malik, Muhammad,Marks, Kevin R.,Schwanz, Heidi A.,German, Nadezhda,Drlica, Karl,Kerns, Robert J.
body text, p. 5214 - 5221 (2011/10/12)
Quinolones rapidly kill bacteria by two mechanisms, one that requires protein synthesis and one that does not. The latter, which is measured as lethal action in the presence of the protein synthesis inhibitor chloramphenicol, is enhanced by N-1 cyclopropyl and C-8 methoxy substituents, as seen with the highly lethal compound PD161144. In some compounds, such as levofloxacin, the N-1 and C-8 substituents are fused. To assess the effect of ring fusion on killing, structural derivatives of levofloxacin and PD161144 differing at C-7 were synthesized and examined with Escherichia coli. A fused-ring derivative of PD161144 exhibited a striking absence of lethal activity in the presence of chloramphenicol. In general, ring fusion had little effect on lethal activity when protein synthesis was allowed, but fusion reduced lethal activity in the absence of protein synthesis to extents that depended on the C-7 ring structure. Additional fused-ring fluoroquinolones, pazufloxacin, marbofloxacin, and rufloxacin, also exhibited reduced activity in the presence of chloramphenicol. Energy minimization modeling revealed that steric interactions of the trans-oriented N-1 cyclopropyl and C-8 methoxy moieties skew the quinolone core, rigidly orient these groups perpendicular to core rings, and restrict the rotational freedom of C-7 rings. These features were not observed with fused-ring derivatives. Remarkably, structural effects on quinolone lethality were not explained by the recently described X-ray crystal structures of fluoroquinolone-topoisomerase IV-DNA complexes, suggesting the existence of an additional drug-binding state. Copyright
Quinoline-3-carboxylic acid derivatives
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, (2008/06/13)
Compounds of formula (I): STR1 (in which R1 is alkoxy, R is alkyl, haloalkyl, alkylamino, cycloalkyl or optionally substituted phenyl, X is chlorine or fluorine and Y is selected from certain specific heterocycles) have excellent antibacterial activity. They may be prepared by introducing the group represented by Y into the corresponding compound in which Y is replaced by a halogen atom.
