Synthesis and activity optimization of herbicidal substituted 4-aryl-1,2,4-triazole-5(1H)-thiones

The process of sorting leads identified via screening can be made more efficient by the application of experimental design strategies. Such strategies were applied during the course of optimization of a series of 4-aryl-1,2,4-triazole-5(1H)-thiones which were initially identified as being herbicidal in greenhouse screens. Through application of a Free-Wilson strategy and subsequent sequential simplex optimization, potency improvements of 25000-fold over the unsubstituted phenyl compound have been realized in a hydroponic cucumber assay. Synthesis of these analogues will be discussed as well as the development of the QSAR model which relates structural modifications to potency