Synthesis and biological properties of a new series of anti-MRSA beta-lactams; 2-(thiazol-2-ylthio)carbapenems.
A series of 1 beta-methylcarbapenems containing variously C-2 substituted thiazol-2-ylthio groups were synthesized, and their in vitro anti-MRSA activity was examined. Among them, 1 beta-methyl-2-(4-arylthiazol-2-ylthio)carbapenems exhibited superior anti-MRSA activity. Introduction of a cationic moiety in the C-2 side chain not only reduced the binding to HSA but also increased the stability against DHP-I, without affecting the anti-MRSA activity. It was also found that the distance between the cationic moiety and the carbapenem skeleton was related to the strength of HSA binding and the stability against DHP-I.
Shinagawa
H
H
Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
Yamaga
H
H
Houchigai
H
H
Sumita
Y
Y
Sunagawa
M
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015780:Carbapenems / Q000138:chemical synthesis* / Q000494:pharmacology; D002511:Cephalosporins / Q000737:chemistry; D004150:Dipeptidases / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; D012709:Serum Albumin; D004150:Dipeptidases; C038937:dipeptidase