Author/Authors :
Hidenori Azami، نويسنده , , J. DAVID BARRETT، نويسنده , , Keiji Matsuda، نويسنده , , Hideo Tsutsumi، نويسنده , , Kenichi Washizuka، نويسنده , , Minoru Sakurai، نويسنده , , Satoru Kuroda، نويسنده , , Fumiyuki Shirai، نويسنده , , Toshiyuki Chiba، نويسنده , , Toshiaki Kamimura، نويسنده , , Masayoshi Murata، نويسنده ,
Abstract :
The synthesis and biological activity of a novel series of 2-alkyl-4-pyrrolidinylthio-β-methylcarbapenems containing a variety of cationic heteroaromatic substituents is described. As a result of these studies, we uncovered a relationship between in vitro antibacterial activity and the length of the alkyl spacer part, and discovered FR20950 , containing a two methylene spacer moiety and an imidazolio group, which possesses a balanced spectrum of antibacterial activity, including Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, FR20950 exhibited excellent urinary recovery, and comparable stability against renal dehydropeptidase-I (DHP-I) to Biapenem. DHP-I stability could be improved by introduction of a substituent on to the imidazole ring.
Keywords :
carbapenems , Antibacterials , cationic heteroaromatics , DHP-I stability.
