A novel 1 beta-methylcarbapenem antibiotic, S-4661. Synthesis and structure-activity relationships of 2-(5-substituted pyrrolidin-3-ylthio)-1 beta-methylcarbapenems.
The synthesis and biological activity of (1R,5S,6S)-2-[(3S,5S)-5-substituted pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1- methylcarbapen-2-em-3-carboxylic acids are described. These compounds exhibit potent antibacterial activity against a wide range of both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. Of these new carbapenems, (1R,5S,6S)-2-[(3S,5S)-5-sulfamoylaminomethyl pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarb apen- 2-em-3-carboxyli c acid (S-4661) showed the most potent and well balanced activity and was selected as a candidate for further evaluation.
Iso
Y
Y
Shionogi & Co., Ltd., Osaka, Japan.
Irie
T
T
Nishino
Y
Y
Motokawa
K
K
Nishitani
Y
Y
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015780:Carbapenems / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000077726:Doripenem; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem