title: Synthesis of novel di- and tricationic carbapenems with potent anti-MRSA activity.
abstract: A new series of 1beta-methyl carbapenems possessing a 6,7-disubstituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and their activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. First, a benzyl moiety was introduced at the C-6 position of imidazo[5,1-b]thiazole attached to the carbapenem. These benzylated molecules showed potent anti-MRSA activity, but poor water solubility. In order to overcome this drawback, we designed and synthesized di- and tricationic carbapenems and finally discovered a novel carbapenem (15i), which exhibited excellent anti-MRSA activity and good water solubility.
authors.affiliation: Process Development Section Kitakami-Plant, Meiji Seika Kaisha, Ltd., 3-3 Kita-Kougyoudanchi, Kitakami-shi, Iwate 024-0012, Japan. takahisa_maruyama@meiji.co.jp
authors.forename: Takahisa
authors.initials: T
authors.lastname: Maruyama
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kano
authors.forename: Mizuyo
authors.initials: M
authors.lastname: Kurazono
authors.forename: Eiki
authors.initials: E
authors.lastname: Shitara
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Iwamatsu
authors.forename: Kunio
authors.initials: K
authors.lastname: Atsumi
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D012995:Solubility
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002412:Cations