Synthesis and biological activity of 1beta-methyl-2-[5'-isoxazoloethenylpyrrolidin-3'-ylthio]carbapenems.
A new series of 1beta-methylcarbapenems 1a-i bearing isoxazoloethenyl groups on the pyrrolidine ring has been prepared and evaluated for in vitro antibacterial activity and stability to DHP-I. Most compounds showed excellent antibacterial activity and high stability to DHP-I superior to that of meropenem. Of these new carbapenems, 1a,b,h exhibited the best combination of antibacterial activity and DHP-I stability.
Kim
D J
DJ
Life Sciences Division, Korea Institute of Science and Technology, Cheongryang, Seoul, South Korea. djk2991@kist.re.kr
Seo
K J
KJ
Lee
K S
KS
Shin
K J
KJ
Yoo
K H
KH
Kim
D C
DC
Park
S W
SW
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D015780:Carbapenems / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D004150:Dipeptidases / Q000378:metabolism; D004355:Drug Stability; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007555:Isoxazoles / Q000494:pharmacology*; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013552:Swine; D013845:Thienamycins / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D007555:Isoxazoles; D013845:Thienamycins; D004150:Dipeptidases; C038937:dipeptidase; D000077731:Meropenem