SAR of Nitroimidazooxazoles

OPC-67683 (Fig. 12; 12a) shows potent antitubercular activity against both replicating and non-replicating bacteria and is equipotent against drug-resistant MTb [143, 159]. Derivatives of these 6-nitro-2,3-dihydroimidazo [2,1-b]oxazoles were not mutagenic in contrast to the structurally similar CGI-17341 (Fig. 12; 11b), with heteroatoms at the side chain of 2-position contributing to the absence of mutage-nicity. Addition of a methyl group at the 2-position was found to improve activity, and the absolute stereochemistry was found to be critical with the R-enantiomer (MIC of 180 nM) being 60-fold more active than the S-enantiomer (Table 3). Subsequent development of R-enantiomers of 6-nitro-2,3-dihydroimidazo [2,1-b] oxazole culminated in identification of lead compound OPC-67683 [159]. Figure 13 compares the SAR for both the oxazine and the oxazole series of antitubercular nitroimidazoles.

Was this article helpful?

0 0

Post a comment