Inhibitors of type III secretion in Yersinia:: Design, synthesis and multivariate QSAR of 2-arvisulfonylamino-benzanilides

Compound 1, 2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-5-chloro-N-(3,4-dichloro-phenyl)-benzamide. was identified as a putative type III secretion inhibitor in Yersinia. and the compound thus has a potential to be used to prevent or treat bacterial infections. A set of seven analogues was svnthesized and evaluated in a type III secretion dependent reporter-gene assay with viable bacterial to give basic SAR. A second set of 19 compounds was obtained by statistical molecular design in the building block and product space and by subsequent synthesis. Evaluation in the reporter-gene assay showed that the compounds ranged from nonactive to compounds more potent than 1. Based on the data multivariate QSAR models were established and the final Hi-PLS model showed good correlation between experimentally determined % inhibition and the calculated % inhibition of the reporter-gene signal. (C) 2007 Elsevier Ltd. All rights reserved.