Synthesis of novel di- and tricationic carbapenems with potent anti-MRSA activity.
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.
Maruyama
Takahisa
T
Process Development Section Kitakami-Plant, Meiji Seika Kaisha, Ltd., 3-3 Kita-Kougyoudanchi, Kitakami-shi, Iwate 024-0012, Japan. takahisa_maruyama@meiji.co.jp
Yamamoto
Yasuo
Y
Kano
Yuko
Y
Kurazono
Mizuyo
M
Shitara
Eiki
E
Iwamatsu
Katsuyoshi
K
Atsumi
Kunio
K
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
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002412:Cations