title: Synthesis and biological activity of novel 1beta-methylcarbapenems with oxyiminopyrrolidinylamide moiety.
abstract: The synthesis and antibacterial activity of novel 1beta-methylcarbapenems 1a-f bearing oxyiminopyrrolidinylamide moiety at C-5 position of pyrrolidine are described. Most compounds exhibited comparable antibacterial activity to meropenem against a wide range of Gram-positive and Gram-negative organisms including Pseudomonas aeruginosa isolates. Of these carbapenems, 1a showed potent and broad spectrum of antibacterial activity and similar stability to DHP-I to meropenem. Against clinical isolates of 40 Gram-negative bacterial species including MDR and ESBL-producing strains, the selected carbapenem 1a possessed excellent in vitro activity except for MDR P. aeruginosa, and was comparable in potency to meropenem.
authors.affiliation: Medicinal Chemistry Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyung Seok
authors.initials: KS
authors.lastname: Lee
authors.forename: Yong Koo
authors.initials: YK
authors.lastname: Kang
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Yoo
authors.forename: Kye Jung
authors.initials: KJ
authors.lastname: Shin
authors.forename: Dong Chan
authors.initials: DC
authors.lastname: Kim
authors.forename: Jae Yang
authors.initials: JY
authors.lastname: Kong
authors.forename: Yeonhee
authors.initials: Y
authors.lastname: Lee
authors.forename: Sook Ja
authors.initials: SJ
authors.lastname: Lee
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Kim
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D011759:Pyrrolidines