Dicationic dithiocarbamate carbapenems with anti-MRSA activity. |
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Authors: | H Imamura N Ohtake H Jona A Shimizu M Moriya H Sato Y Sugimoto C Ikeura H Kiyonaga M Nakano R Nagano S Abe K Yamada T Hashizume H Morishima |
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Institution: | Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo-3, Tsukuba 300-2611, Ibaraki, Japan. imamrahk@banyu.co.jp |
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Abstract: | A new class of 1 beta-methylcarbapenems bearing a doubly quaternarized 1,4-diazabicyclooctane (DABCO) substituted dithiocarbamate moiety at the C-2 side chain was prepared, and the biological profiles of the compounds, including in vitro and in vivo anti-MRSA activity and DHP-I susceptibility, were evaluated to identify a carbapenem derivative that was superior to BO-3482 (1). As a result, we discovered a 1 beta-methyl-2-4-(4-carbamoylmethyl-1,4-diazabicyclo2,2,2]octanediium-1-yl)methyl-1,2,3,6-tetrahydropyridinylthiocarbonylthio]carbapenem, 14a showing greater than 2-fold better anti-MRSA activity in a mouse infection model and 3-fold better DHP-I susceptibility as compared with BO-3482 (1). |
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