Quantitative Structure-Activity Relationships of Fluazinam and Related Fungicidal N-Phenylpyridinamines

Preventive Activity against Botrytis cinerea

Abstract

Fluazinam, an N-phenylpyridinamine compound, is a fungicide, now on sale or under development all over the world by Ishihara Sangyo Kaisha Ltd. Fluazinam was selected after lead optimization of N-phenylpyridinamine skeleton which was obtained by lead development from acaricidal compound. In this study, the preventive activity against Botrytis cineyea of N-phenylpyridinamines was analyzed by the technique of QSAR (ALS method) to elucidate the role of substituents on both of the pyridine and benzene rings, and also to obtain suggestion about the mode of action of this series of compounds. Structure-activity relationships on the substituents of the pyridine ring were explained by the combination of electronic, steric and hydrophobic parameters, while those on the substituents of the benzene ring were rather complicated. Instead, the molecular orbital calculations (AM1) suggested that the reactivity of the chlorine atom at the meta position of the benzene ring seemed to be correlated with the activity very well. Some molecular properties of several fungicidal compounds with clear mode of actions were calculated. As a result, the LUMO levels of fluazinam was very similar to the characteristically low LUMO levels of sulfhydryl-enzyme inhibitors and uncouplers. The results of this study revealed that the substitution pattern of fluazinam was the most desirable. The suggestion that some reaction of fluazinam with SH- or other groups might be involved in the mode of action of this compound was obtained.