Computer-Assisted Proposition of Promising Aryloxyacetic Acid Derivatives as HPPD Inhibitors.

A series of aryloxyacetic acid derivatives have demonstrated promising herbicidal performance by inhibition of the hydroxyphenylpyruvate deoxygenase (HPPD) enzyme. We hereby applied quantitative structure-activity relationship (QSAR) and docking strategies to model and chemically understand the bioactivities of these compounds and subsequently propose unprecedented analogues aiming at improving the herbicidal and environmental properties. Bulky halogens at the 2-, 3-, 4-, and 6-positions of an aromatic ring, CF in 4-position, and the 2-NO group in a phenyl ring appear to favor the HPPD inhibition.