 |
In general, closing the window
is a problem for the developers of new antimicrobial compounds. To illustrate how one
might proceed along these lines we investigated the effect of fluoroquinolone structure on
the window opening using S. aureus as a test organism (19). The upper compound is
moxifloxacin, a C-8-methoxy derivative. It shows a window opening of 12 when the ratio of
MPC to MIC(99) is taken as the window opening index. The C-8-H derivative of
moxifloxacin, shown as the second molecule in the column, has a window opening almost 3
times as great. This is expected from what was said above about the effect of a
C-8-methoxy group. Interestingly, ciprofloxacin, the third compound in the series, has a
window opening that is the same as moxifloxacin. Adding a C-8-methoxy group to
ciprofloxacin should close the window beyond the value seen with moxifloxacin. This is the
case, as shown with the bottom compound. |
