18527-21-4Relevant articles and documents
Dealkylative intercepted rearrangement reactions of sulfur ylides
Empel, Claire,Hock, Katharina J.,Koenigs, Rene M.
supporting information, p. 338 - 341 (2019/01/09)
Sulfur ylides are well-known to undergo sigmatropic rearrangement reaction. Herein, we describe a novel reactivity of sulfur ylides, which provides access to the product of a formal functional group metathesis upon dealkylative interception of the rearrangement process. Using a simple iron catalyst and in situ generated diazoalkanes this method provides access to α-mercaptoacetonitrile derivatives.
Nanomolar potency and metabolically stable inhibitors of kidney urea transporter UT-B
Anderson, Marc O.,Zhang, Jicheng,Liu, Yan,Yao, Chenjuan,Phuan, Puay-Wah,Verkman
experimental part, p. 5942 - 5950 (2012/07/30)
Urea transporters, which include UT-B in kidney microvessels, are potential targets for development of drugs with a novel diuretic ('urearetic') mechanism. We recently identified, by high-throughput screening, a triazolothienopyrimidine UT-B inhibitor, 1, that selectively and reversibly inhibited urea transport with IC50 = 25.1 nM and reduced urinary concentration in mice (Yao et al.J. Am. Soc. Nephrol., in press). Here, we analyzed 273 commercially available analogues of 1 to establish a structure-activity series and synthesized a targeted library of 11 analogues to identify potent, metabolically stable UT-B inhibitors. The best compound, {3-[4-(1,1-difluoroethyl)benzenesulfonyl]thieno[2,3-e][1,2,3]triazolo[1,5-a] pyrimidin-5-yl}thiophen-2-ylmethylamine, 3k, had IC50 of 23 and 15 nM for inhibition of urea transport by mouse and human UT-B, respectively, and ～40-fold improved in vitro metabolic stability compared to 1. In mice, 3k accumulated in kidney and urine and reduced maximum urinary concentration. Triazolothienopyrimidines may be useful for therapy of diuretic-refractory edema in heart and liver failure.
