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. published the artcile< Development of (6R)-2-Nitro-6-[4-(trifluoromethoxy)phenoxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (DNDI-8219): A New Lead for Visceral Leishmaniasis>, Category: chlorides-buliding-blocks, the main research area is DNDI8219 preparation lead visceral leishmaniasis; aryl nitroimidazooxazine.
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 analog 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. Addnl. profiling earmarked R-6 as the favored backup development candidate.
Journal of Medicinal Chemistry published new progress about Drug metabolism (metabolic stability). 162046-61-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H4ClF3O2, Category: chlorides-buliding-blocks.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics