Synthesis and biological activity of novel 1beta-methylcarbapenems with oxyiminopyrrolidinylamide moiety.
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.
Lee
Ji Hoon
JH
Medicinal Chemistry Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
Lee
Kyung Seok
KS
Kang
Yong Koo
YK
Yoo
Kyung Ho
KH
Shin
Kye Jung
KJ
Kim
Dong Chan
DC
Kong
Jae Yang
JY
Lee
Yeonhee
Y
Lee
Sook Ja
SJ
Kim
Dong Jin
DJ
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
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D011759:Pyrrolidines