Thompson, Andrew M. published the artcileHeteroaryl ether analogues of an antileishmanial 7-substituted 2-nitroimidazooxazine lead afford attenuated hERG risk: In vitro and in vivo appraisal, COA of Formula: C5H2ClF3N2, the main research area is nitroimidazo oxazine heteroaryl ether analog preparation antileishmanial; Chagas disease; Leishmaniasis; Pharmacokinetics; Pretomanid; hERG inhibition; in vivo efficacy.
Previous investigation of the potent antileishmanial properties of antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines with biaryl side chains led to our development of a new clin. candidate for visceral leishmaniasis (DNDI-0690). Within a collaborative backup program, a racemic monoaryl lead (3) possessing comparable activity in mice but a greater hERG liability formed the starting point for our pursuit of efficacious second generation analogs having good solubility and safety. Asym. synthesis and appraisal of its enantiomers first established that chiral preferences for in vivo efficacy were species dependent and that neither form afforded a reduced hERG risk. However, in line with our findings in a structurally related series, less lipophilic heteroaryl ethers provided significant solubility enhancements (up to 16-fold) and concomitantly attenuated hERG inhibition. One promising pyridine derivative (49) displayed 100% oral bioavailability in mice and delivered a 96% parasite burden reduction when dosed at 50 mg/kg in a Leishmania donovani mouse model of visceral leishmaniasis.
European Journal of Medicinal Chemistry published new progress about Drug bioavailability. 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, COA of Formula: C5H2ClF3N2.