Lee, Sujin published the artcileNanomolar-Potency 1,2,4-Triazoloquinoxaline Inhibitors of the Kidney Urea Transporter UT-A1, SDS of cas: 25983-14-6, the main research area is triazolo quinoxaline analog preparation renal urea transporter inhibitor diuretic.
Urea transporter A (UT-A) isoforms encoded by the Slc14a2 gene are expressed in kidney tubule epithelial cells, where they facilitate urinary concentration UT-A1 inhibition is predicted to produce a unique salt-sparing diuretic action in edema and hyponatremia. Here we report the discovery of 1,2,4-triazoloquinoxalines and the anal. of 37 synthesized analogs. The most potent compound, 8ay, containing 1,2,4-triazolo[4,3-a]quinoxaline-substituted benzenesulfonamide linked by an aryl ether, rapidly and reversibly inhibited UT-A1 urea transport by a noncompetitive mechanism with IC50 ≈ 150 nM; the IC50 was ∼2 μM for the related urea transporter UT-B encoded by the Slc14a1 gene. Mol. modeling suggested a putative binding site on the UT-A1 cytoplasmic domain. In vitro metabolism showing quinoxaline ring oxidation prompted the synthesis of metabolically stable 7,8-difluoroquinoxaline analog 8bl, which when administered to rats produced marked diuresis and reduced urinary osmolality. 8bl has substantially improved UT-A1 inhibition potency and metabolic stability compared with prior compounds
Journal of Medicinal Chemistry published new progress about Diuretics. 25983-14-6 belongs to class quinoxaline, name is 2,3,6,7-Tetrachloroquinoxaline, and the molecular formula is C8H2Cl4N2, SDS of cas: 25983-14-6.
Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider