Synthesis and insecticidal activity of N-(5-phenylpyrazin-2-yl)-benzamide derivatives: Elucidation of mode of action on chitin biosynthesis through symptomology and genetic studies

Abstract

Among the six-membered heterocycles, the pyrazine ring is poorly explored in crop protection and does not feature in any product listed in the current IRAC MoA classification. In an effort to identify new leads for internal research, we synthesized a series of N-(5-phenylpyrazin-2-yl)-benzamide derivatives and evaluated them for their insecticidal activity. N-(5-phenylpyrazin-2-yl)-benzamide derivatives 3 were prepared using an automated two-step synthesis protocol. These compounds were tested for their initial biological activity against a wide range of sucking and chewing insect pests and found to be active against lepidopterans only. More detailed experiments, including symptomology studies on the diamondback moth, Plutella xylostella (L.) and the Egyptian cotton leafworm, Spodoptera littoralis (Boisduval) showed that analog 3q causes severe abnormalities in the lepidopteran cuticle leading to larval mortality. Compound 3q shows strong potency against both P. xylostella and S. littoralis, whereas analog 3i shows better potency against S. littoralis causing also impaired cuticular structure and death of the larvae. Additionally, P. xylostella genetic studies showed that compound 3q resistance is linked to Chitin Synthase 1. Our studies show that N-(5-phenylpyrazin-2-yl)-benzamide derivatives 3, and in particular analogs 3i and 3q, act as insect growth modulator insecticides. Conformational similarities with lufenuron are discussed.