1263188-72-2Relevant 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.
, 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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, (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.
