title: Discovery of novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenems.
abstract: Novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenems were designed and synthesized to provide J-111,347 (1a) as the first example of an exceptionally broad-spectrum antibiotic, showing activity against methicillin-resistant Staphyloccocus aureus (MRSA) as well as Pseudomonas aeruginosa. Further derivation of 1a afforded J-111,225 (2a), J-114,870 (3a), and J-114,871 (3b). which showed improved safety profiles and retained broad-spectrum antibacterial activities.
authors.affiliation: Banyu Tsukuba Research Institute, Ibaraki, Japan. imamrahk@banyu.co.jp
authors.forename: H
authors.initials: H
authors.lastname: Imamura
authors.forename: N
authors.initials: N
authors.lastname: Ohtake
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: S
authors.initials: S
authors.lastname: Sakuraba
authors.forename: R
authors.initials: R
authors.lastname: Nagano
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.forename: S
authors.initials: S
authors.lastname: Abe
authors.forename: C
authors.initials: C
authors.lastname: Suzuki-Sato
authors.forename: I
authors.initials: I
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Hashizume
authors.forename: H
authors.initials: H
authors.lastname: Morishima
mesh_terms: D000818:Animals; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D003292:Convulsants; D004150:Dipeptidases / Q000378:metabolism; D015195:Drug Design; D004827:Epilepsy / Q000139:chemically induced; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D015780:Carbapenems; D003292:Convulsants; D011758:Pyrroles; D004150:Dipeptidases; C038937:dipeptidase