Thienamycin derivatives (4) having a cyclic amidine moiety at the C-2 position were prepared. The susceptibility to renal dehydropeptidase-1 and the antimicrobial activity of these compounds were determined. Their structure-activity relationships are also discussed.Carbapenem antibiotics, represented by thienamycin (THM),1~8) have been reported to be hy-f THMhave been extensively undertaken to obtain DHP-1-resistant THMderivatives having potent antimicrobial activities. Recently, Merck chemists have found7) that synthetic THMderivatives (3) having a 2-amidinoalkyl side chain at the C-2 position of carbapenem nucleus showed antimicrobial activities almost equal to, and resistance to DHP-1 greater than, that of iV-formimidoyl THM (MK0787).8~10)In our previous papers,11'12) derivatization of the S-a-position of the cysteamine side chain of THMhas been reported. As a part of the derivatization of this series, we have prepared THMderivatives (4) having a cyclic amidine moiety, in which the nitrogen atom and the S-tf-position of 2-amidinoalkyl moiety are cyclized as in Fig. 1. The present paper deals with the synthesis of these derivatives and the biological data in this series.
ChemistryIn a previous paper,13) we have described a facile method for the preparation of cyclic amidines,
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