- Syntheses and biological activities of new N1-aryl substituted quinolone antibacterials
-
A series of quinolones with a systematically varied substitution at the phenyl ring at N1 has been synthesized. Three lipophilicity descriptors (log K, log P, R(m)) and the pK(a) values have been determined as well as the microbiological activity: The MIC
- Juergens, Jens,Schedletzky, Holger,Heisig, Peter,Seydel, Joachim K.,Wiedemann, Bernd,Holzgrabe, Ulrike
-
p. 179 - 190
(2007/10/03)
-
- Effect of Lipophilicity at N-1 on Activity of Fluoroquinolones against Mycobacteria
-
The dramatic increase in drug resistant Mycobacterium tuberculosis has caused a resurgence in research targeted toward these organisms.As part of a systematic study to optimize the quinolone antibacterials against mycobacteria, we have prepared a series of N-1-phenyl-substituted derivatives to explore the effect of increasing lipophilicity on potency at this position.The compounds, synthesized by the modification of a literature procedure, were evaluated for activity against Gram-negative and Gram-positive bacteria, Mycobacterium fortuitum and Mycobacterium smegmatis, and the results correlated with log P, pKa, and other attributes.The activity of the compounds against the rapidly growing, less hazardous organism M. fortuitum was used as a measure of M. tuberculosis activity.The results demonstrate that increasing lipophilic character by itself does not correlate with increased potency against mycobacteria.Rather, intrinsic activity against Gram-negative and/or Gram-positive bacteria is the governing factor for corresponding activity against mycobacteria.
- Renau, Thomas E.,Sanchez, Joseph P.,Shapiro, Martin A.,Dever, Julie A.,Gracheck, Stephen J.,Domagala, John M.
-
p. 2974 - 2977
(2007/10/02)
-
- Quinoline antibacterial compounds
-
Quinoline compounds having the formula: STR1 wherein R is a phenyl group or an aromatic heterocyclic group, Z is an aliphatic heterocyclic group or an amine, and R1 is hydrogen or a carboxy-protecting group. The compounds here disclosed have an
- -
-
-