Novel cephalosporin derivatives possessing a bicyclic heterocycle at the 3-position. Part I: Synthesis and biological activities of 3-(benzothiazol-2-yl)thiocephalosporin derivatives, CP0467 and related compounds.

Abstract A series of cephalosporin derivatives with various bicyclic heterocycles at the C-3 position was synthesized and evaluated for antibacterial activity. Among them CP0467 ( 3a ) showed excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) (MIC 90 =6.25 μg/mL), and extremely high affinity for the penicillin binding protein 2′ of MRSA (I 50 =0.49 μg/mL). Furthermore, 3a showed a long-acting pharmacokinetic profile in mice (AUC ∞ =482.3 μg/h/mL and T 1/2 =1.9 h).