Synthesis and biological evaluation of novel tricyclic carbapenems (trinems).
Synthesis of new tricyclic carbapenems (trinems) with a pyrrolidinyl moiety at the C-4 position of the tricyclic ring and their antimicrobial activities were studied. These trinems showed potent activities against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Among them, (4R)-[(S)-pyrrolidin-3-ylthiomethyl]trinem (14a) exhibited good activity against MRSA in vitro and in vivo.
Kanno
O
O
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd, Tokyo, Japan.
Shimoji
Y
Y
Ohya
S
S
Kawamoto
I
I
D000818:Animals; D015780:Carbapenems / Q000138:chemical synthesis* / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus; D013329:Structure-Activity Relationship
D015780:Carbapenems