Discovery of a Novel Series of Phenyl Pyrazole Inner Salts Based on Fipronil as Potential Dual-Target Insecticides

Abstract

A series of novel phenyl pyrazole inner salt derivatives based on fipronil were designed and synthesized in the search for dual-target insecticides. These compounds were designed to target two families of nicotinic acetylcholine receptors and γ-aminobutyric acid receptors. The insecticidal activities of the new compounds against diamondback moth (Plutella xylostella) were evaluated. The results of bioassays indicated that most of the inner salts showed moderate to high activities, of which the phenyl pyrazole inner salts containing quinoline had excellent biological activity. Previous structure-activity relationship studies revealed that a suitable structure of the quaternary ammonium salts was critical for the bioactivity of phenyl pyrazole inner salts, which contribute to exposing the cationic nitrogen to bind to the receptor (for instance, nicotinic acetylcholine receptors) and possibly interact with the receptor via hydrogen bonding and cooperative π-π interaction. The present work demonstrates that the insecticidal potency of phenyl pyrazole inner salts holds promise for the development new dual-target phenyl pyrazole insecticides.

3,5–Bis(2–Hydroxyphenyl)–1H–1,2,4–Triazole Derivatives: Synthesis, Crystal Structure and Insecticidal Activity

“…Compound 3 a was prepared from key intermediate 2 by condensing with 80% hydrazine hydrate, where excessive hydrazine hydrate was quenched in time at the end of the reaction. The condensation reaction of intermediate 2 with various phenylhydrazine derivatives furnished compounds 3 b , 3 c and 3 d . Compounds 4 a – 4 d were prepared by esterification of the compounds 3 c and 3 d with anhydrous methanol and ethanol respectively, and to avoid the hydrolysis of the products, the acid‐catalyst was quenched with saturated aqueous NaHCO 3 solution in time .…”

“…[6] It is worth noting that pyrazole is a highly efficient pharmacophore that is widely used in pesticide design, and many pyrazolyl heterocyclic derivatives exhibited favorable insecticidal activity. [2,[7][8][9][10] 4- [3,5-bis(2-hydroxyphenyl) -1,2,4-triazol-1-yl] benzoic acid (deferasirox) developed by Swiss Novartis Pharmaceuticals is an orally active iron chelating agent, which has been approved by the US FDA in 2005. [11,12] The compound possesses a stable 1,2,4-triazole heterocyclic ring and two phenol moieties can form intermolecular hydrogen bonds with heteroatom.…”

Direct chiral separations of the enantiomers of phenylpyrazole pesticides and the metabolites by HPLC

“…10 For the control of certain pests such as mites, fleas, lice, etc., S-(+)-fipronil is more effective. 12,13 To reduce the resistance risk and the side effects to nontarget aquatic organisms, many fipronil derivatives have been synthesized and commercialized, such as flufiprole{1- [2,6- Figure 1), which are also chiral. However, it is highly toxic to aquatic organisms, particularly crustaceans, and many insects have developed high resistance.…”

“…11 Fipronil has been widely used for the protection of crops, such as cotton and rice. 12 Since the introduction of the modifying group, flufiprole and ethiprole have a lower toxicity or higher activity than fipronil. 12,13 To reduce the resistance risk and the side effects to nontarget aquatic organisms, many fipronil derivatives have been synthesized and commercialized, such as flufiprole{1- [2,6- Figure 1), which are also chiral.…”

Key Intermediates: A Simple and Highly Selective Synthesis of 5-<i>Amino</i>-1-<i>aryl</i>-1<i>H</i>-<i>pyrazole</i>-4-<i>carbonitriles</i> for Applications in the Crop Protection

“…Fipronil is the first phenyl pyrazole insecticide introduced in the market [20]. This aryl pyrazole is highly effective against a significant range of economically important insect pests, and it has become a cornerstone in insect control programs in both non-crop and crop pest control situations in many areas of the world [21].…”