Moxidectin

Moxidectin Property

Melting point:

132 °C

Boiling point:

790.0±70.0 °C(Predicted)

Density 

1.23±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

≥128 mg/mL in EtOH; ≥129.4 mg/mL in DMSO; ≥3.27 mg/mL in H2O with gentle warming and ultrasonic

form 

Solid

pka

12.46±0.70(Predicted)

color 

White to Almost white

optical activity

139.1°(C=0.01 g/mI, CHCL3 , 20°C, 589nm)

Stability:

Light Sensitive

InChIKey

YZBLFMPOMVTDJY-LSGXYNIPSA-N

Safety

Hazard Codes 

T,N

Risk Statements 

25-50

Safety Statements 

45-61-24/25

RIDADR 

2588

WGK Germany 

3

RTECS 

PY5438800

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

29322090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H400Very toxic to aquatic life

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P273Avoid release to the environment.

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

P391Collect spillage. Hazardous to the aquatic environment

P405Store locked up.

Moxidectin Chemical Properties,Usage,Production

Description

Moxidectin is a macrocyclic lactone endectocide and a derivative of nemadectin. It reduces fecal nematode egg counts by 98.4 and 99.8% in naturally infected calves when administered subcutaneously at doses of 0.2 and 0.3 mg/kg, respectively. Moxidectin (0.2 and 0.3 mg/kg) reduces the worm burden of O. ostertagi and T. axei in the abomasum, and Cooperia species and N. helvetianus in the small intestine, of naturally infected calves. It potentiates GABA-gated currents in Xenopus oocytes expressing rat α₁β₂γ₂ subunit-containing GABA_A receptors with an EC₅₀ value of 11.8 nM. Formulations containing moxidectin have been used in the treatment of onchocerciasis, as well as in the prevention and treatment of parasitic infections in veterinary medicine.

Uses

anthelmintic, antiparasitic

Uses

Moxidectin is a macrocyclic lactone and semisynthetic derivative of nemadectin. Moxidectin is a parasiticide used for the prevention and control of heartworm and intestinal worms. Moxidectin is is fou nd in veterinary medicine used to treat animals such as dogs, cats, horses, cattle and sheep.

Uses

Moxidectin is a semi-synthetic milbemycin derived from nemadectin by selective oxidation followed by methyloximation. Moxidectin was patented in 1991 as an anthelmintic for internal parasite control. The presence of the methyloxime affords moxidectin a greater hydrophobicity and longer biological half-life compared to nemadectin. Moxidectin binds selectively to parasite glutamate-gated chloride ion channels and disrupts neurotransmission leading to paralysis and death of the parasite.

Definition

ChEBI: Moxidectin is a milbemycin.

Synthesis

1. The solid product (0.087 mol) was dissolved in 640 mL of 1,4-dioxane and anhydrous sodium acetate (0.13 mol), acetic acid (0.028 mol) and methoxyamine hydrochloride (0.14 mol) were added sequentially under nitrogen protection. The reaction mixture was stirred at room temperature for 10 hours. The progress of the reaction was monitored by TLC and after confirming the complete reaction of the ingredients, the reaction was terminated by adding 1000 mL of pure water. The reaction mixture was extracted with 1000 mL of ethyl acetate and the extraction was repeated once. The organic phases were combined, dried with anhydrous sodium sulfate and concentrated to give 78.4 g solid. 2. The above solid was dissolved in 4120 mL of ethanol and 1760 mL of pure water was added to adjust the ethanol concentration to 70% (v/v). After filtration to remove insoluble material, 7840 mL of pure water was added for dilution. Extraction was repeated with 13,720 mL of heptane. The heptane layers were combined and concentrated until crystals precipitated, stopping the concentration. Cooled to 20 °C with slow stirring, filtered to separate the crystals and dried under vacuum at 45 °C, -0.08 MPa to give a white solid (0.071 mol). 3. Dissolve the dried crystals (0.071 mol) in 1270 mL of anhydrous methanol and cool to 0 °C. A solution of p-toluenesulfonic acid (0.13 mol) in methanol (120 mL) was added slowly dropwise, keeping the reaction temperature at 0 °C. After dropwise addition, the reaction was continued for 4 h. The reaction progress was monitored by HPLC. The reaction solution was transferred to 2780 mL of saturated sodium bicarbonate solution and washed thoroughly. It was extracted twice with 1270 mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate and concentrated to give a solid product (0.054 mol). 4. The resulting solid was dissolved in 23030 mL of 70% (v/v) aqueous methanol and filtered to remove insoluble material. The filtrate was upsampled onto a HP20 macroporous resin column and eluted with 80% (v/v) methanol aqueous solution. The eluate was detected by HPLC and the fraction with 98% purity was collected. Concentrate the eluate to 35% (v/v) methanol and stop the concentration. Cooled to 20°C, stirred slowly for 5 h. The precipitate was withdrawn and dried to give moxidectin (0.015 mol, 96.2% content).

Veterinary Drugs and Treatments

In dogs and cats, moxidectin with lufenuron is indicated as a once a month topical preventative for the prevention of heartworm, flea adulticide, ear mites (cats) and treatment for hookworms, roundworms, and whipworms (dogs). It has also been successfully used as a treatment for generalized demodicosis.
In cattle, moxidectin is indicated for the treatment and control of the following internal [adult and fourth stage larvae (L4)] and external parasites: Gastrointestinal roundworms: Ostertagia ostertagi (adult and L4, including inhibited larvae), Haemonchus placei (adult), Trichostrongylus axei (adult and L4), Trichostrongylus colubriformis (adult), Cooperia oncophora (adult), Cooperia punctata (adult), Bunostomum phlebotomum (adult), Oesophagostomum radiatum (adult), Nematodirus helvetianus (adult); Lungworm: Dictyocaulus viviparus (adult and L4); Cattle Grubs: Hypoderma bovis, Hypoderma lineatum Mites: Chorioptes bovis, Psoroptes ovis (Psoroptes communis var. bovis); Lice: Linognathus vituli, Haematopinus eurysternus, Solenopotes capillatus, Damalinia bovis; Horn flies: Haematobia irritans. To control infections and to protect from reinfection from Ostertagia ostertagi for 28 days after treatment and from Dictyocaulus viviparus for 42 days after treatment.
In sheep, oral moxidectin is indicated for the control of Haemonchus contortus (adult and L4), Teladosrsagia circumcincta & trifurcata (adult and L4), Trichostrongylus colubriformis, axei, & vitrinius (adult & L4), Cooperia curticei & oncophora (adult and L4), Oesophagostomum columbianum & venolosum (adult & L4), and Nematodirus battus, filicollis, & spathiger (adult & L4).
In horses and ponies, moxidectin is indicated for the treatment and control of the following stages of gastrointestinal parasites: Large strongyles: Strongylus vulgaris (adults and L4L5 arterial stages); Strongylus edentatus (adults and tissue stages); Triodontophorus brevicauda (adults); Triodontophorus serratus (adults); Small strongyles (adults and larvae): Cyathostomum spp. (adults); Cylicocyclus spp. (adults); Cylicostephanus spp. (adults); Gyalocephalus capitatus (adults); undifferentiated lumenal larvae; Encysted cyathostomes: late L3 and L4 mucosal cyathostome larvae; Ascarids: Parascaris equorum (adults and L4 larval stages); Pin worms: Oxyuris equi (adults and L4 larval stages); Hair worms: Trichostrongylus axei (adults); Large-mouth stomach worms: Habronema muscae (adults); Horse stomach bots: Gasterophilus intestinalis (2nd and 3rd instars). When combined with praziquantel, additional coverage against Anoplocephala spp. occurs.

References

[1] Tetrahedron Letters, 1988, vol. 29, # 21, p. 2595 - 2598
[2] Patent: CN104017001, 2016, B. Location in patent: Paragraph 0018; 0049; 0050
[3] Patent: CN104277050, 2016, B. Location in patent: Paragraph 0101-0104