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group exhibits an extended antimicrobial spectrum including anti-pseudomonal activity and high stability to renal dehydropeptidase-I (DHP-I)1}. From the structureactivity relationship studies, we found that the basicity of the C-2 side chain is important for exhibiting antimicrobial activity especially against Pseudomonas aeruginosa by supporting good permeability through the outer membrane(OM)5). However, the strength of the basicity does not directly correlate with the antipseudomonal activity5). We also found that the Ifimethyl group of carbapenem compoundsnot only improves their DHP-I stability, but also variably affects their antimicrobial activity1'5'6). Regarding the effect of C-6 substituent, there are several studies on natural occurring or synthesized carbapenems which have a different substituent on C-6 from thienamycin (i.e., hydroxyethyl group)7~11}.

Structure-activity Relationships of 1.BETA.-Methyl-carbapenems to Antimicrobial Activity: Effect of C-6 Substituent.