CP0569, A New Broad-Spectrum Injectable Carbapenem. Part 1: Synthesis and Structure–Activity Relationships

Abstract A series of 1β-methylcarbapenems bearing an (imidazo[5,1- b ]thiazolium-6-yl)methyl moiety, a 5,5-fused heterobicycle, at the C-2 position was synthesized and evaluated for in vitro antibacterial activities. CP0569 ( 1r ) and its analogues showed potent antibacterial activities against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria, including Pseudomonas aeruginosa . Moreover, CP0569 ( 1r ) exhibited stronger antibacterial activity against MRSA and higher resistance to renal dehydropeptidase-1 (DHP-1) than any currently marketed carbapenems, that is, imipenem (IPM), panipenem (PAPM), and meropenem (MEPM).