Simple oxidation of pyrimidinylhydrazones to triazolopyrimidines and their inhibition of Shiga toxin trafficking

Abstract

The oxidative cyclisation of a range of benzothieno[2,3-d]pyrimidine hydrazones (7a-e) to the 1,2,4-triazolo [4,3-c]pyrimidines (8a-e) catalysed by lithium iodide or to the 1,2,4-triazolo[1,5-c]pyrimidines (10a-e) with sodium carbonate is presented. A complementary synthesis of the 1,2,4-triazolo[1,5-c]pyrimidines (10a-e) starting from the amino imine 11 is also reported. The effect of these compounds on Shiga toxin (STx) trafficking in HeLa cells and comparison to the previously reported Exo2 is also detailed

Inhibitors of the Cellular Trafficking of Ricin

“…However, LG186 appears to have a residual inhibition of other ArfGEFs. Other derivatives of Exo2 have also been designed to conserve the protective effects of Exo2 against Shiga toxin and to decrease its cytotoxicity [45,46]. Exo2 and its derivatives have therefore provided more selective tools than BFA to decipher membrane trafficking in mammalian cells.…”

Synthesis of new sulfur-linked di- and triheterocyclic compounds containing thienotriazolopyrimidine and triazolothiadiazole moieties

“…Much attention has been recently paid to the synthesis of thieno-1,2,4-triazolopyrimidines and sulfur-containing 1,2,4-triazoles (3-thio-1,2,4-triazoles) because of their biological activities and potential therapeutic use (Almajan et al , 2005 ;Contour -Galc é ra et al, 2005 ;Nagamatsu et al , 2007 ;Prasad et al , 2008 ;Siwek et al , 2008 ;Guetzoyan et al , 2010 ). We previously designed and synthesized thienotriazolopyrimidine derivatives with promising biological activity (Jo et al , 2008 ;Son , 2010 , 2011 ).…”

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

“…Clarkson and co-workers have prepared a range of benzothieno-fused 1,2,4-triazolo[4,3- c ]pyrimidines and 1,2,4-triazolo[1,5- c ]pyrimidines by the oxidative cyclisation of benzothieno[2,3- d ]pyrimidine hydrazones. The investigation has also suggested the important ability as inhibitors of Shiga toxin trafficking for protecting HeLa cells [9]. …”