3-Keto-11,12-carbazate derivatives of 6-O-methylerythromycin A synthesis and in vitro activity.
The 11,12-cyclic carbazate of 3-keto-6-O-methylerythromycin A (4) was prepared. This compound shows in vitro antibacterial activity comparable to erythromycin A (1) against erythromycin-susceptible organisms and increased activity against some erythromycin-resistant organisms. Using 4 as a lead, a series of analogues was prepared by acylation or alkylation of the carbazate nitrogen. Several of the N-alkylated derivatives showed dramatically improved antibacterial activity against both susceptible and resistant organisms as compared to erythromycin A.
Griesgraber
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G
Abbott Laboratories, Abbott Park, Illinois 60064, U.S.A.
Or
Y S
YS
Chu
D T
DT
Nilius
A M
AM
Johnson
P M
PM
Flamm
R K
RK
Henry
R F
RF
Plattner
J J
JJ
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004917:Erythromycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048628:Ketolides; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
C100405:3-keto-6-O-methylerythromycin A 11,12-cyclic carbazate; D000900:Anti-Bacterial Agents; D048628:Ketolides; D004917:Erythromycin