Novel 1beta-methylcarbapenems with isoxazoloethenyl moieties containing carboxylic acid sodium salt.
The synthesis of novel 1beta-methylcarbapenems 1a,b having sodium 5-(3- and 5-carboxylic acid)isoxazoloethenyl 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. The selected sodium 3-carboxylic acid derivative 1a possessed excellent DHP-I stability and advanced pharmacokinetic parameters in comparison with 2 and meropenem.
Lee
Kyung Seok
KS
Medicinal Chemistry Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Korea.
Kang
Yong Koo
YK
Yoo
Kyung Ho
KH
Kim
Dong Chan
DC
Shin
Kye Jung
KJ
Paik
Young-Sook
YS
Kim
Dong Jin
DJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D019540:Area Under Curve; D015780:Carbapenems / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000032:analysis*; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D008826:Microbial Sensitivity Tests
C476323:1 beta-methylcarbapenem; D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002264:Carboxylic Acids