Dicationic dithiocarbamate carbapenems with anti-MRSA activity

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-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 mo use infection model and 3-fold better DHP-I susceptibility as compared with BO-3482 (1). (C) 2001 Elsevier Science Ltd. All rights reserved.