A factorially designed set of 3‐substituted 2‐aryl‐4,5,6,7‐tetrahydroindazoles was synthesized and their herbicidal properties were evaluated using regression analysis. For optimal activity, the substituent at position 3 should be neither strongly hydrophobic nor hydrophilic and should have a small minimum radius. A study of the mechanism of action indicated that the tetrahydroindazoles are inhibitors of the enzyme protoporphyrinogen oxidase.

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-l,2,4triazole-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 25 000-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.

No abstract

No abstract

A random source PSI electron‐accepting herbicide lead, ethyl 1,2,4‐benzotriazine‐3‐acetate 1, was optimized using molecular probing, bioisosteric replacement, Free‐Wilson analysis, Sequential Simplex Optimization, and ultimately linear regression analysis. Some variables in the initial regression equations were found to be cross correlated, representing the same factors as revealed by factor analysis. The technique of prefiltering potential variables for linear regression analysis utilizing factor analysis is exemplified. For the set of 1 analogs, eleven independent factors were identified which were then submitted to linear regression analysis. The resulting equations are statistically more secure, all terms being independent. These equations are discussed in the context of known SAR for herbicidal PSI electron acceptors, especially the bipyridiniums.