Synthesis and biological evaluation of novel 1 beta-methylcarbapenems with isothiazoloethenyl side chains.
The synthesis of novel 1 beta-methylcarbapenems 1a,b bearing isothiazoloethenyl moieties at C-5 position of pyrrolidine ring and their biological evaluation are described. Both compounds showed potent and well-balanced antibacterial activity as well as high stability to DHP-I. Especially, 5-isothiazole derivative 1a exhibited excellent DHP-I stability and advanced pharmacokinetics profiles, compared to 5-isoxazole derivative 2, imipenem, and meropenem.
Kang
Yong Koo
YK
Medicinal Chemistry Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
Lee
Kyung Seok
KS
Yoo
Kyung Ho
KH
Shin
Kye Jung
KJ
Kim
Dong Chan
DC
Lee
Chang-Seok
CS
Kong
Jae Yang
JY
Kim
Dong Jin
DJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D015780:Carbapenems / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D007202:Indicators and Reagents; D000077731:Meropenem; D051379:Mice; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction; D051381:Rats; D013329:Structure-Activity Relationship; D013845:Thienamycins / Q000494:pharmacology
C476323:1 beta-methylcarbapenem; D000900:Anti-Bacterial Agents; D015780:Carbapenems; D007202:Indicators and Reagents; D013845:Thienamycins; D000077731:Meropenem