Synthesis and antibacterial activity of C11, C12-cyclic urea analogues of ketolides.
C11, C12-cyclic urea analogues of ketolides were designed and synthesized by use of a novel ketene acetal intermediate. This intermediate enabled introduction of an amino group at C12 stereospecifically and in high yield. The resulting cyclic urea ketolides appear to have in vitro activity similar to that of telithromycin which contains a C11, C12 cyclic carbamate moiety. Some of the C2 fluorinated compounds have improved potency against erm-containing Streptococcus pyogenes.
Kaneko
Takushi
T
Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. takushikaneko@gmail.com
McMillen
William
W
Lynch
Meghan Keaney
MK
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D048628:Ketolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013297:Streptococcus pyogenes / Q000187:drug effects; D014508:Urea / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D048628:Ketolides; D014508:Urea