Antimycobacterial Activities of Novel 5-(1H-1,2,3-Triazolyl)Methyl Oxazolidinones

The antibacterial activities of a series of triazolyl oxazolidinones against Mycobacterium tuberculosis strain in vitro and in vivo in a mice model are presented. Most active compounds were noncytotoxic against VERO cells with acceptable selectivity indexes (SI) as measures of compound tolerability. Structure activity relationships (SARs) revealed that analogs with alkylcarbonyl (IC(90): < 0.2 to 0.422 μg/mL) and arylcarbonyl (IC(90): < 0.2 to 2.103 μg/mL) groups at the piperazine 4N-position-displayed potent antimycobacterium activities, comparable to the methanesulfonyl (IC(90): < 0.2 μg/mL) analog, linezolid (IC(90): < 0.2 μg/mL), and isoniazid (IC(90): < 0.034 μg/mL). The furanylcarbonyl derivative also displayed potent activity, while the arylsulfonyl analogs were inactive. Of the triazolyl oxazolidinones, the morpholino (PH-27) derivative with medium bioavailability in plasma was most active in vivo, but relatively less efficacious than isoniazid.