Imazalil

Description

Imazalil (also known as Enilconazole) is a kind of topical mycotic agent that used for the treatment of fungi infections. It is primarily used for the treatment of fungi attracted to tubers of the crops, including Fusarium spp, Phoma spp, and Helminthosporum solani which reduces the crop quality. It can also be applied to citrus fruits. In addition, it can also be used for the treatment of Microsporum spp and Aspergillus spp infections occurring in the dogs, either as a single topic agent or being combined with oral administrated itraconazole or griseofulvin. The mechanism of action of Imazalil is through suppressing the biosynthesis pathway of ergosterol through blocking the demethylation process. 

References

http://www.vetbook.org/wiki/dog/index.php?title=Enilconazole
https://en.wikipedia.org/wiki/Enilconazole
https://www.mysciencework.com/publication/show/f0382c741754e9200388abe8cf2f0133

Description

Description

Imazalil is an imidazole fungicide that inhibits ergosterol biosynthesis. Imazalil inhibits the growth of various fungi in vitro including P. italicum, A. niger, U. maydis, B. alii, and C. cucumerinum in a pH-dependent manner (MICs = 0.005-2 μg/ml at pH 7). It inhibits S. cerevisiae, but not rat liver microsomal, cytochrome P450 enzymes (CYPs; IC₅₀s = 0.088 and 80 μM, respectively), as well as aromatase CYP19 from human placental microsomes (IC₅₀ = 0.34 μM). Imazalil activates the murine pregnane X receptor (PXR) in a concentration-dependent manner in a cell-based reporter assay. It increases hepatic CYP3A11 and CYP2B10 mRNA levels in mice when administered at a dose of 100 mg/kg. Imazalil also increases Ki-67-positive nuclei in liver sections and hepatic MCM2 mRNA levels, markers of cell proliferation, in mice when co-administered with the murine constitutive androstane receptor (mCAR) agonist TCPOBOP . Formulations containing imazalil have been used to control fungal infection in agriculture.

Uses

antifungal

Uses

As a disinfectant for stable and kennel equipment; experimentaly as an agricultural fungicide.

Uses

Imazalil is a systemic fungicide with protective and curative action. It is used for the control of a wide range of fungal diseases on fruit, vegetables and ornamentals, powdery mildew on roses and storage diseases of citrus fruit, pome fruit, bananas and seed potatoes. It is also used as a seed dressing, for control of diseases of cereals (particularly Fusarium and Helminthosporium spp.), and it is particularly active against benzimidazole-resistant strains of plant-pathogenic fungi.

Definition

ChEBI: 1-[2-(allyloxy)-2-(2,4-dichlorophenyl)ethyl]imidazole is a member of the class of imidazoles in which the hydrogen at position 1 is replaced by a 2-(allyloxy)-2-(2,4-dichlorophenyl)ethyl group. It is a member of imidazoles, an ether and a dichlorobenzene.

General Description

Slightly yellow to brown solidified oil. Non-corrosive. Used as a fungicide.

Air & Water Reactions

Water soluble.

Reactivity Profile

Imazalil is an imidazole derivative.

Safety Profile

Poison by ingestion and intraperitoneal routes. Experimental reproductive effects. A skin and eye irritant. When heated to decomposition it emits toxic fumes of Cland NOx.

Synthesis

288-32-4

107-05-1

4252-78-2

35554-44-0

This embodiment provides a method for preparing 1-(2-(allyloxy)-2-(2,4-dichlorophenyl)ethyl)-1H-imidazole comprising the steps of: to a 500 mL three-necked flask under stirring conditions were added sequentially 185 g (4.0 mol) of formic acid, 45.1 g (0.2 mol) of 2,4-dichloro-2'-chloroacetophenone, 10 g of triethylamine ( 0.1 mol) and RuCl2(PPh3)3 5 g (0.01 mol). The mixture was heated to 70°C and kept reacting for 9 hours. After completion of the reaction, it was cooled to 50°C and subjected to reduced pressure distillation until no liquid dripped out, followed by cooling to room temperature. Sodium hydroxide 16 g (0.4 mol) and imidazole 22 g (0.32 mol) were added to the reaction mixture, heated to 100°C and kept reacting for 5 hours, then cooled to room temperature. 3-Chloropropene 24 g (0.32 mol) was added dropwise, heated to 105°C and kept the reaction for 6 hours. After the reaction was completed, it was cooled to room temperature, 320 mL of water was added and the crude product was obtained by filtration. The crude product was dissolved in 100 mL of ethanol, heated and refluxed for 1 h, then filtered at room temperature to obtain the pure product 1-(2-(allyloxy)-2-(2,4-dichlorophenyl)ethyl)-1H-imidazole 28.7 g, yield 64.4%, purity ≥ 98% by liquid phase analysis, melting point 50.9-52.0 °C.

Veterinary Drugs and Treatments

Although no dosage forms are currently commercially available for topical use in the USA, Enilconazole is used topically for treating dermatophytosis in small animals and horses using compounded products. A commercially available topical rinse Imaverol (Janssen) 10% is available with canine, bovine and equine use labeling in many countries. Intranasal instillation of enilconazole after plaque debridement has also been shown useful in treating nasal aspergillosis in small animals.
Use of topical enilconazole on cats with dermatophytosis is somewhat controversial as there are apparently no products with feline labeling available in Europe or Canada. There are preliminary reports of safely and successfully using enilconazole on dermatophytic cats in combination with oral itraconazole.
A topical product and a poultry environmental disinfectant product (Clinafarm EC) is available in the USA. It is technically illegal to use this product other than it is labeled; it is an EPA licensed product in the USA.

Metabolic pathway

Published information is available on the metabolism of imazalil in plants and soils. The principal metabolite in plants and soils is 1-[2-(2,4- dichlorophenyl)-2-hydroxyethyl]-1H-imidazole.

Degradation

Imazalil is very stable to hydrolysis in dilute acids and alkalis at room temperature, in the absence of light. It is also stable to light under normal storage conditions.

References

[1] Patent: CN108191765, 2018, A. Location in patent: Paragraph 0023-0034