Abstract
A series of novel pleuromutilin derivatives with substituted 6-methylpyrimidine moieties was designed, synthesized, and evaluated for their antibacterial activities. Most of the tested compounds exhibited potent antibacterial activities against Staphylococcus aureus ATCC 25923 (S.aureus-25923), methicillin-resistant Staphylococcus epidermidis ATCC 51625 (MRSE-51625), methicillin-resistant Staphylococcus aureus BNCC 337371 (MRSA-337371), Streptococcus dysgalactiae (S.dysgalactiae) and Streptococcus agalactiae (S.agalactiae). Compounds 5c and 5g were the most active and displayed bacteriostatic activities against MRSA. Invivo mouse systemic infection experiment showed that 5c significantly improved the survival rate of mice (ED50=18.02mg/kg), reduced the bacterial load and alleviated the pathological changes in the lungs of the affected mice.
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