The discovery of dinotefuran: a novel neonicotinoid

Abstract

Dinotefuran (MTI-446: (RS)-1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine) is a new neonicotinoid commercialized by Mitsui Chemicals. Research led to this novel neonicotinoid by the removal of the chloropyridine or chlorothiazole ring that had been considered as indispensable for neonicotinoides. The research advanced as follows; (1) selection of acetylcholine for the lead compound, (2) recognition of the insecticidal advantages of 3-methoxypropyl compounds, (3) synthesis of (+/-)-tetrahydro-3-furylmethyl compounds by cyclization of the 3-methoxypropyl moiety. It resulted in dinotefuran which has a (+/-)-tetrahydro-3-furylmethyl moiety instead of a halogenated aromatic heterocyclic ring, and belongs to the third-generation neonicotinoids (sub-class: furanicotinyl compounds).

Pharmacophore of neonicotinoid insecticides

“…13) Later, chlorothiazolyl and tetrahydrofuranyl groups were found as an activator and applied to commercial products, 14,15) and quite recently we found 5-fluoro-6-chloro-3-pyridylmethyl group as an equally strong activator. 16,17) These heterocyclic groups have been assumed to function as an H-bond acceptor, as shown in Fig.…”

Synthesis and Structure-Activity Relationships of Dinotefuran Derivatives: Modification in the Tetrahydro-3-furylmethyl Part

“…At the end of the conformational search, we obtained 16 and 78 energy-minimized conformers for dinotefuran (2) and compound 10 with energy ranges (the energy difference between the highest and the lowest energy conformer) of 4.5 and 8.1 kcal/mol, respectively. Three conformations out of 16 have the receptor-associated hydrogen bond acceptor within 2 Å from that of the active conformer when the imidazolidine parts are superposed onto superposition A. Twenty-four percent of all energy-minimized conformations took superposition A on the basis of the Boltzmann probability distribution at room temperature (300 kelvin).…”

“…1). 1,2) The chloronicotinyl and thianicotinyl compounds have pyridine-like moieties, as is the case for the pyridine ring in nicotine (1), and the furanicotinyl compound dinotefuran (2) has a characteristic (Ϯ)-tetrahydro-3-furylmethyl moiety.…”

Synthesis, Characterization and Anti-Inflammatory Activity of Hydrazones Bearing 5-Nitro-Furan Moiety and 5-Iodo-Vanillin Hybrid

“…[1,2] Furan derivatives exhibits wide range of insecticidal and phytocidal activities. [3,4] Furthermore, they were found to show interesting pharmacological properties viz., anti-depressant, anti-anxiolytic, anti-inflammatory, anti-hypertensive, anti-glaucoma, anti-arrhythmatic, anti-ulcer, anti-diuretic, anti-neoplastic, anti-ageing, anti-parkinsonism, anti-histaminic. [5,6] Hydrazide-hydrazones represent a class of organic compounds embedded with azomethine group (-NH-N=CH-) linked with carbonyl group that have occupied a prominent place in the branch of medicinal chemistry and exhibits various pharmaceutical applications [7] Some of the examples of chemotherapeutic agents that are known to contain hydrazide-hydrazone moiety are nitrofurazone, [8] furazolidone [9,10] and nitrofurantoin.…”