Author/Authors :
Hideaki Imamura، نويسنده , , Norikazu Ohtake، نويسنده , , Hideki Jona، نويسنده , , Aya Shimizu، نويسنده , , Minoru Moriya، نويسنده , , Hiroki Sato، نويسنده , , Yuichi Sugimoto، نويسنده , , Chinatsu Ikeura، نويسنده , , Hideo Kiyonaga، نويسنده , , Masato Nakano، نويسنده , , Rie Nagano، نويسنده , , Shinnosuke Abe، نويسنده , , Koji Yamada، نويسنده , , Terutaka Hashizume، نويسنده , , Hajime Morishima، نويسنده ,
Abstract :
A new class of 1β-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 1β-methyl-2-[4-(4-carbamoylmethyl-1,4-diazabicyclo[2,2,2]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).
