1 beta-Methyl-2-(5-substituted pyrrolidin-3-ylthio)carbapenems. 3. Synthesis and antibacterial activity of BO-2727 and its related compounds.
The synthesis and biological activity of (1R,5S,6S)-2-[(3S,5S)- 5-substituted pyrrolidin-3-ylthio]- 6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid in which hydroxy-substituted aminoethyl, aminopropyl, and aminobutyl groups were introduced as substituents, are described. These derivatives showed potent antibacterial activity against Gram-positive and Gram-negative bacteria including P. aeruginosa. Among them, lenapenem (BO-2727, 7b), carrying an (R)-1-hydroxy-3-(N-methylamino)propyl group, was selected as a development candidate.
Ohtake
N
N
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan.
Okamoto
O
O
Mitomo
R
R
Kato
Y
Y
Yamamoto
K
K
Haga
Y
Y
Fukatsu
H
H
Nakagawa
S
S
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D015780:Carbapenems / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D013055:Spectrophotometry, Infrared
D000900:Anti-Bacterial Agents; D015780:Carbapenems; C085890:BO 2727