1131004-99-3Relevant academic research and scientific papers
Antitubercular Nitroimidazoles Revisited: Synthesis and Activity of the Authentic 3-Nitro Isomer of Pretomanid
Thompson, Andrew M.,Bonnet, Muriel,Lee, Ho H.,Franzblau, Scott G.,Wan, Baojie,Wong, George S.,Cooper, Christopher B.,Denny, William A.
, p. 1275 - 1280 (2017/12/26)
A published study of structural features associated with the aerobic and anaerobic activities of 4- and 5-nitroimidazoles had found that the 3-nitro isomer of pretomanid, 8, displayed interesting potencies, including against nitroreductase mutant Mycobacterium tuberculosis. However, recent nuclear magnetic resonance analyses of two trace byproducts, isolated from early process optimization studies toward a large-scale synthesis of pretomanid, raised structural assignment queries, particularly for 8, stimulating further investigation. Following our discovery that the reported compound was a 6-nitroimidazooxazole derivative, we developed a de novo synthesis of authentic 8 via nitration of the chiral des-nitro imidazooxazine alcohol 26 in trifluoroacetic or acetic anhydride, and verified its identity through an X-ray crystal structure. Unfortunately, 8 displayed no antitubercular activity (MICs > 128 μM), whereas the second byproduct (3′-methyl pretomanid) was eight-fold more potent than pretomanid in the aerobic assay. These findings further clarify target specificities for bicyclic nitroimidazoles, which may become important in the event of any future clinical resistance.
Structure-activity relationships of antitubercular nitroimidazoles. 1. structural features associated with aerobic and anaerobic activities of 4 - And 5-nitroimidazoles
Kim, Pilho,Zhang, Liang,Manjunatha, Ujjini H.,Singh, Ramandeep,Patel, Sejal,Jiricek, Jan,Keller, Thomas H.,Boshoff, Helena I.,Barry III, Clifton E.,Dowd, Cynthia S.
experimental part, p. 1317 - 1328 (2009/12/07)
The 4-nitroimidazole PA-824 is active against aerobic and anaerobic Mycobacterium tuberculosis(Mtb)while 5-nitroimidazoles like metronidazole are active against only anaerobic Mtb. We have synthesized analogues of both 4 - and 5-nitroimidazoles and explor
