Novel dithiocarbamate carbapenems with anti-MRSA activity.
A new series of 1beta-methyl carbapenems, in which a disubstituted-aminothiocarbonylthio moiety was attached to the C-2 position of the carbapenem nucleus, were prepared and evaluated for anti-MRSA activity. These derivatives showed good in vitro antibacterial activity against high-level MRSA, and the finding of good affinity for PBP-2' supported these results. Some of the compounds having favorable protein-binding affinity showed excellent in vivo anti-MRSA activity.
Ohtake
N
N
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan.
Imamura
H
H
Jona
H
H
Kiyonaga
H
H
Shimizu
A
A
Moriya
M
M
Sato
H
H
Nakano
M
M
Ushijima
R
R
Nakagawa
S
S
D000818:Animals; D001426:Bacterial Proteins; D001798:Blood Proteins / Q000378:metabolism; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D015169:Colony Count, Microbial; D004150:Dipeptidases / Q000737:chemistry; D006602:Hexosyltransferases; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008813:Mice, Inbred ICR; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism; D010458:Peptidyl Transferases; D011485:Protein Binding; D051381:Rats; D012640:Seizures / Q000139:chemically induced; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013552:Swine; D013845:Thienamycins / Q000494:pharmacology
D001426:Bacterial Proteins; D001798:Blood Proteins; D015780:Carbapenems; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D013845:Thienamycins; D015378:Imipenem; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D004150:Dipeptidases; C038937:dipeptidase; D002267:Muramoylpentapeptide Carboxypeptidase