1263188-75-5Relevant academic research and scientific papers
Development of (6 R)-2-Nitro-6-[4-(trifluoromethoxy)phenoxy]-6,7-dihydro-5 H -imidazo[2,1- b] [1,3]oxazine (DNDI-8219): A New Lead for Visceral Leishmaniasis
Thompson, Andrew M.,O'Connor, Patrick D.,Marshall, Andrew J.,Blaser, Adrian,Yardley, Vanessa,Maes, Louis,Gupta, Suman,Launay, Delphine,Braillard, Stephanie,Chatelain, Eric,Wan, Baojie,Franzblau, Scott G.,Ma, Zhenkun,Cooper, Christopher B.,Denny, William A.
supporting information, p. 2329 - 2352 (2018/03/26)
Discovery of the potent antileishmanial effects of antitubercular 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles and 7-substituted 2-nitro-5,6-dihydroimidazo[2,1-b][1,3]oxazines stimulated the examination of further scaffolds (e.g., 2-nitro-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]oxazepines), but the results for these seemed less attractive. Following the screening of a 900-compound pretomanid analogue library, several hits with more suitable potency, solubility, and microsomal stability were identified, and the superior efficacy of newly synthesized 6R enantiomers with phenylpyridine-based side chains was established through head-to-head assessments in a Leishmania donovani mouse model. Two such leads (R-84 and R-89) displayed promising activity in the more stringent Leishmania infantum hamster model but were unexpectedly found to be potent inhibitors of hERG. An extensive structure-activity relationship investigation pinpointed two compounds (R-6 and pyridine R-136) with better solubility and pharmacokinetic properties that also provided excellent oral efficacy in the same hamster model (>97% parasite clearance at 25 mg/kg, twice daily) and exhibited minimal hERG inhibition. Additional profiling earmarked R-6 as the favored backup development candidate.
Biarylmethoxy 2-nitroimidazooxazine antituberculosis agents: Effects of proximal ring substitution and linker reversal on metabolism and efficacy
Thompson, Andrew M.,Blaser, Adrian,Palmer, Brian D.,Franzblau, Scott G.,Wan, Baojie,Wang, Yuehong,Ma, Zhenkun,Denny, William A.
, p. 3804 - 3809 (2015/08/24)
Abstract Certain biaryl analogues of antitubercular drug PA-824 displayed enhanced in vivo efficacies yet retained some susceptibility towards oxidative metabolism; therefore, two new strategies were explored to address this. Ortho-substitution of the pro
NITROIMIDAZOOXAZINE AND NITROIMIDAZOOXAZOLE ANALOGUES AND THEIR USES
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Page/Page column 34, (2011/02/25)
The current invention pertains to nitroimidazooxazine and nitroimidazooxazole analogues, their methods of preparation, and uses of the compounds as treatment for Mycobacterium tuberculosis, for use as anti-tubercular drugs, for use as anti-protozoal agents with unexpectedly high potency against Trypanosoma cruzi or Leishmania donovani, and for the treatment of other microbial infections.
