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infection is responsible for a global pandemic. New drugs are needed that do not show cross-resistance with the existing front-line therapeutics. A triazine antitubercular hit led to the design of a related pyrimidine family. The synthesis of a focused series of these analogs facilitated exploration of their activity, cytotoxicity, and physiochemical and absorption-distribution-metabolism-excretion properties. Select pyrimidines were then evaluated for their pharmacokinetic profiles in mice. The findings suggest a rationale for the further evolution of this promising series of antitubercular small molecules, which appear to share some similarities with the clinical compound PA-824 in terms of activation, while highlighting more general guidelines for the optimization of small-molecule antitubercular agents.

Synthesis and Antibacterial Activity of Pyrroloaryl-Substituted Oxazolidinones. -A series of pyrroloaryl-substituted oxazolidinones are prepared and screened against a panel of susceptible and resistant Gram-positive bacteria. (VII), (XI) and (XII) show superior or comparable in vitro antibacterial activity as compared to linezolid. -(PAGET*, S. D.; FOLENO, B. D.; BOGGS, C. M.; GOLDSCHMIDT, R. M.; HLASTA, D. J.; WEIDNER-WELLS, M. A.; WERBLOOD, H. M.; WIRA, E.; BUSH, K.; MACIELAG, M. J.; Bioorg. Med. Chem. Lett. 13 (2003) 23, 4173-4177; Johnson and Johnson Pharm. Res. Dev., Raritan, NJ 08869, USA; Eng.) -M. Bohle 13-093

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