Synthesis and structure-activity relationships of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' or C-7 catechol or related aromatics.
A series of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' catechol-containing (pyridinium-4-thio)methyl groups and 2-isocephems with C-7 catechol related aromatics have been prepared and evaluated for antimicrobial activity. It turns out that these compounds have highly potent activity against Gram-negative bacteria, especially resistant pathogens such as Pseudomonas aeruginosa. The most active compound of the series was (6S,7S)-7-[2-(2-aminothiazol-4-yl)-2-[(Z)-[(1,5-dihydroxy-4-pyr idon-2-yl) methoxy]imino]acetamido]-3-[[[(4-methyl-5-carboxymethyl)thiazol-2- yl] thio]methyl]-8-oxo-1-aza-4-thiabicyclo [4.2.0] oct-2-ene-2-carboxylic acid which exhibited potent in vitro activity against clinically isolated P, aeruginosa and Acinetobacter baumanii which is also resistant to many anti-infectives, and good in vivo efficacy against clinically isolated P aeruginosa.
Tsuji
K
K
Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Tsubouchi
H
H
Yasumura
K
K
Matsumoto
M
M
Ishikawa
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001398:Aztreonam / Q000737:chemistry / Q000494:pharmacology; D002396:Catechols / Q000737:chemistry; D002442:Ceftazidime / Q000737:chemistry / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
C105406:7-(2-(2-aminothiazol-4-yl)-2-(((1,5-dihydroxy-4-pyridon-2-yl)methoxy)imino)acetamido)-3-((((4-methyl-5-carboxymethyl)thiazol-2-yl)thio)methyl)-8-oxo-1-aza-4-thiabicyclo(4.2.0)oct-ene-2-carboxylic acid; D000900:Anti-Bacterial Agents; D002396:Catechols; D002511:Cephalosporins; D002442:Ceftazidime; D001398:Aztreonam; C034221:catechol