Selamectin Antiparasitic Drug Insecticide Animal Raw Material

English name：Selamectin insecticide

CAS number：220119-17-5

Molecular formula：C43H63NO11

Molecular weight 769.97

EINECS number815-979-7

Microbial metabolites; Pharmaceutical intermediates; Antiparasitic drugs; Raw drug substance; Insecticide; Medical raw materials; Raw materials for animal use; Agricultural and animal raw materials; Pharmaceutical chemical industry; Chemical reagents; AntChemicalbookhelmintic; ectoparasiticide; API; API apis - deworming; Chemical reagents - raw materials for animal use; Control substance; Pharmaceutical raw materials

Molecular structure:

melting point>180°C

boiling point：917.0±65.0 °C(Predicted)

density 1.35±0.1 g/cm3(Predicted)

condition of storage Sealed in dry,Room Temperature

Solubility: chloroform (dissolved in small amount), dichloromethane (dissolved in small amount, heated), DMSO (dissolved in small amount)

acidity coefficient(pKa)10.34±0.70(Predicted)

Morphological solid

Color is white to yellow

Stability and moisture absorption

InChI=1/C43H63NO11/c1-24-11-10-14-30-23-50-40-36(44-48)27(4)19-33(43(30,40)47)41(46)52-32-20-31(16-15-25(2)38(24)53-35-21-34(49-6)37(45)28(5)51-35)54-42(22-32)18-17-26(3)39(55-42)29-12-8-7-9-13-29/h10-11,14-15,19,24,26,28-29,31-35,37-40,45,47-48H,7-9,12-13,16-18,20-23H2,1-6H3/b11-10+,25-15+,30-14+,44-36-/t24-,26-,28-,31+,32-,33-,34-,35-,37-,38-,39-,40+,42+,43+/s3

Overview

Selamectin (also known as silamectin) is produced by a new strain of recombinant Streptomyces aviriformis, developed by Pfizer of the United States. It is obtained by chemical synthesis structure modification of doramectin. In July 1999, it was first marketed in the United Kingdom under the trade name Revolution.

Mechanism of action

The mechanism of action of selamicin is the same as that of other abamicin drugs. On the one hand, selamicin can act as an agonist of γ-aminobutyric acid (GABA) to trigger the release of presynaptic GABA, which in turn causes the increase of membrane permeability to Cl¯. On the other hand, selamicin can open glutamate controlled chloride channels, which in turn causes the increase of Cl¯ permeability and leads to membrane potential hyperpolarization. Thus blocking the transmission of nerve signals, causing rapid, fatal Chemicalbook and non-spastic neuromuscular paralysis and death. "Trematodes and tapeworms do not have GABA neurotransmitters and glutamate controlled Cl¯ channels, so they do not have repellent effects." The drug binding sites of invertebrates are peripheral tissues, while the drug binding sites of mammals are in the central nervous system. Due to the blood-brain barrier, the drug can rarely enter the brain tissue, so the drug is safe for most mammals.

Purpose

The safety of selamicin has been greatly improved, and it has good effects on oral and injection. It is an in vivo and in vitro insecticide mainly against adult fleas, filarial worms and mange of pet cats and dogs.

Preparation

Step 1Preparation of SL1 crude product 20kgDL and 92kg acetone were added to the 300L hydroreactor, and N2 was replaced 3 times by vacuum, stirring was stopped, and 200g of Wilkinson catalyst was added, N2 was replaced 3 times and H2 was replaced 3 times. The reaction was carried out for 3-4 hours at 35-40℃ with hydrogen pressure of 0.3-0.4Mpa. The peak area of DL raw material was less than 1.0% under HPLC monitoring, and the reaction was stopped and N2 replaced. The outer bath 40-50℃ pump was concentrated and evaporated under reduced pressure to obtain 21kg crude product with a purity of 89.3%. Preparation of Step 2SL2 A 500L stainless steel reaction kettle was added with 21kgSL1 and 200kg isopropanol, and the temperature was 20.2 ° C under stirring in a turbid state. Slowly add isopropanol hydrochloric acid solution 50kg(containing hydrochloric acid gas 1.8kg), about 20 minutes to end, nitrogen broke the vacuum and kept warm under nitrogen protection at 22-24℃ stirring for about 0.5h, the system dissolved and stirred for 2 hours HPLC monitoring, SL1< 6%, stop the reaction, the reaction solution is poured into 500kg ice water. Extraction was performed by adding 250kg of dichloromethane, the aqueous layer was further extracted with 120kg of dichloromethane, the organic layer was combined, washed once with 5% sodium bicarbonate, and each time washed three times with 5% salt water. The organic addition of 20kg anhydrous sodium sulfate was dried for 1h, the extracted solid was eluted with 30kg dichloromethane, and the concentrated dry product was 20.5kg with a purity of 83.5%. Step 3The preparation of SL3 N2 protection, 500L stainless steel reactor added 250kg dichloromethane, step 2 obtained 20.5kgSL2 crude stirring under the addition of 40kg electrolyzer manganese dioxide, manganese dioxide with dichloromethane wetting, nitrogen protection at room temperature (20-25℃) stirring for 1.5-2.5 hours, HPLChemicalbookC monitoring, SL2< 1.0%, stop the reaction, pad diatomite, suction filtration, dichloromethane leaching filter cake, combined filtrate, external bath 45-50℃ water pump concentration dry to get crude 21.5kg, purity 84%. Step 4SL (selamectin) preparation of crude N2 protection, 500L stainless steel kettle added SL321.5kg and 200kg isopropanol obtained in step 3, stir dissolution. Heat preservation at 10-15℃, vacuum pumped into 10.5kg hydroxylamine hydrochloride dissolved in 30kg distilled water solution, for 1-2 hours, after the nitrogen gas broke the vacuum protection, heat preservation at 25-30℃ stirring reaction for 3-5 hours, HPLC monitoring, SL3< 1.0%, stop the reaction, the reaction liquid was pumped into 500kg ice water, Extraction was performed by adding 250kg dichloromethane, the aqueous layer was then extracted with 125kg dichloromethane, the organic layer was combined and washed once with 100kg5% sodium bicarbonate and again with 100kg5% salt water. The dry crude product was concentrated at 22kg with a water pump at 45 to 50 ° C to 85% purity in an external bath. Step 5SL (selamicin) refinement add 55kg toluene to the 22kg crude product obtained in step 5, heat up to 45-50 ° C, dissolve, naturally cool down to room temperature (25-30 ° C), then cool down to 0-5 ° C and stir for 12-15 hours, extract 45.8kg of wet product, sample drying and quantitative 23kg, Vacuum oven water bath 40-43℃ for 12h, discharge 13.8kg, purity 96%. The total yield of steps 1 to 5 was 59.5%, and the final product was more than 99.4% pure. Analysis of the final pure selamectin obtained in step 5 showed that the purity of selamectin was 99.446%, with total impurities < 0.6% and all single impurities < 0.2%.

Biological activity

Selamectin, a semisynthetic macrolide, is an antiparasitic agent and insect repellent. Selamectin activation of neurons and pharyngeal muscle glutamic acid chlorine ion channel gating (glutamate - gatedchChemicalbookloridechannels), in order to prevent the evil silk worm, lymphatic silk worm and worm infections. Selamectin is also a potent P-glycoprotein substrate and inhibitor with an IC50 of 120nM

In VITRO Studies

The transport of radiolabelled Selamectin through Caco-2 monolayers shows that Selamectin is P-glycoprotein (P-gp) substrates with a secretory/absorptive ratio of 4.7. Selamectin inhibits the efflux of Rh-123 from peripheral blood lymphocytes (PBL) and the concentration of inhibition is similar to that of Verapamil.

In vivo study

A single administration of 6 mg/kg topical Selamectin given every two months could effectively prevent B. malayi infection in cats. Application of topical Selamectin twice a year could block circulating microfilariae.

Safety Information

WGK Germany3

H.S code 2932206000

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