Toltrazuril

Base Information

• Chemical Name: Toltrazuril
• CAS No.: 69004-03-1
• Molecular Formula: C18H14F3N3O4S
• Molecular Weight: 425.388
• Hs Code.: 29336990
• NSC Number: 759176
• UNII: QVZ3IAR3JS
• DSSTox Substance ID: DTXSID90219063
• Nikkaji Number: J22.790K
• Wikipedia: Toltrazuril
• Wikidata: Q1470932
• NCI Thesaurus Code: C72601
• RXCUI: 1535930
• ChEMBL ID: CHEMBL2104931
• Mol file: 69004-03-1.mol

Synonyms:BAY i 9142;BAY i-9142;BAY-i 9142;Baycox;toltrazuril

Chemical Property of Toltrazuril

Chemical Property:

• Appearance/Colour: Powder
• Melting Point: 194-196°C
• Refractive Index: 1.64
• PKA: 6.47±0.20(Predicted)
• PSA: 111.39000
• Density: 1.54 g/cm³
• LogP: 2.93710
• Storage Temp.: 0-6°C
• Solubility.: Toltrazuril is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide (DMF), which should be purged with an inert gas. The solubility of toltrazuril in ethanol is approximately 1 mg/ml and approximately 25 mg/ml in DMSO and DMF.
• XLogP3: 4.4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 4
• Exact Mass: 425.06571160
• Heavy Atom Count: 29
• Complexity: 655

Purity/Quality:

99% ^*data from raw suppliers

Toltrazuril ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi,N
• Hazard Codes: N,Xi
• Statements: 50/53-36/37/38
• Safety Statements: 60-61-37/39-26

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=C(C=CC(=C1)N2C(=O)NC(=O)N(C2=O)C)OC3=CC=C(C=C3)SC(F)(F)F
• Description: Toltrazuril (Baycox?,Procox?) is a triazinon drug thathas broad-spectrum anticoccidial and antiprotozoalactivity. It is not commercially available in the UnitedStates, but it is available in other countries. It is activeagainst both asexual and sexual stages of coccidia byinhibiting nuclear division of schizonts and microga-monts and the wall-forming bodies of macrogamonts. Itmay also be useful in the treatment of neonatal porcinecoccidiosis, EPM, and canine hepatozoonosis. Toltrazuril and its major metabolite ponazuril (toltrazuril sulfone, Marquis) are triazine-based antiprotozoal drugs that have specific activity against apicomplexan coccidial infections. Toltrazuril is not available within the United States.
• Physical properties: Toltrazuril is white or off-white color crystalline powder, and odorless is molten in the methanol part omitted at ethyl acetate, dichloromethane, Polyethylene Glycol, α-adjoin in the organic solvents such as pyrrolidone, propylene glycol and dissolve, and is insoluble in water.
• Uses: Toltrazuril is an antiprotozoal agent that is widely used to prevent coccidia parasite infection in veterinary applications. The effectiveness of treatment appears to depend on the coccidian species, development stage of the parasite, and level of infection. Labelled analog of a triazinetrione anticoccidial. Coccidiostat. Toltrazuril is found to be highly effective against coccidia and is used in controlling coccidiosis. It is acting against all intracellular development stages of coccidia of the merogony (asexual multiplication) and gamogony (sexual phase). All stages are destroyed, thus the mode of action is coccidiocidal.
• Clinical Use: Swine: Toltrazuril has been shown to reduce the signs of coccidiosis in naturally infected nursing pigs when a single oral 20–30 mg/kg BWdose is given to 3 to 6-dayold pigs (Driesen et al., 1995). Clinical signs were reduced from 71 to 22% of nursing pigs, and diarrhea and oocyst excretion were also decreased by the single oral treatment. Approved products carry a 77-daywithdrawal time in the United Kingdom. Calves and lambs: Toltrazuril is used for the prevention of clinical signs of coccidiosis and reduction of coccidia shedding in calves and lambs as a single dose treatment. Withdrawal times in the United Kingdom are 63 and 42 days for calves and lambs, respectively. Dogs: For hepatozoonosis, toltrazuril given orally at 5 mg/kg BW every 12 hours for 5 days or given orally at 10 mg/kg BW every 12 hours for 10 days caused remission of clinical signs in naturally infected dogs in 2–3 days (Macintire et al., 2001). Unfortunately, most treated dogs relapsed and eventually died from hepatozoonosis. In puppies with Isospora sp. infection, treatment with 0.45 mg emodepside in combination with 9 mg/kg BW toltrazuril (Procox?, Bayer Animal Health) reduces fecal oocyst count by 91.5–100%. There was no difference in duration of diarrhea when treatment was begun after the onset of clinical signs during patent infection (Altreuther et al., 2011). Cats: In kittens experimentally infected with Isospora spp., treatment with a single oral dose of 0.9 mg emodepside in combination with 18 mg/kg BW toltrazuril (Procox?, Bayer AnimalHealth) reduces oocyst shedding by 96.7–100% if given during the prepatent period (Petry et al., 2011). Horses: Toltrazuril has also been used for the treatment of EPM. This drug is safe, even at high doses. Current recommended treatments are 5–10 mg/kg orally for 28 days. Despite the favorable efficacy with toltrazuril, its use has diminished in horses because of better availability of other effective drugs.

Technology Process of Toltrazuril

There total 6 articles about Toltrazuril which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 81.0%

3-methyl-1-[3-methyl-4-(4-(trifluoromethylsulfanyl)phenoxy)phenyl]biuret (106310-18-3) + Diethyl carbonate (105-58-8,76619-83-5) → toltrazuril (69004-03-1)

Guidance literature:

3-methyl-1-[3-methyl-4-(4-(trifluoromethylsulfanyl)phenoxy)phenyl]biuret; Diethyl carbonate; With sodium methylate; In toluene; at 50 ℃; for 4h;

With acetic acid; In water; toluene; at 70 ℃; pH=7; Reagent/catalyst; Solvent; Temperature;

Reference yield: 80.6%

(4-trifluoromethylthio)phenol (461-84-7) + 1-(4-iodo-3-methylphenyl)-3-methyl-1,3,5-triazine-2,4,6-trione → toltrazuril (69004-03-1)

Guidance literature:

With potassium phosphate; copper(l) iodide; N-(2-phenylphenyl)-N′-benzyl oxalamide; In acetonitrile; at 90 ℃; for 24h; Inert atmosphere;

Reference yield:

N-methyl-N'-[3-methyl-4-[4-[(trifluoromethyl)thio]phenoxy]phenyl] imidodicarbonic diamide (106310-17-2) + Diethyl carbonate (105-58-8,76619-83-5) → toltrazuril (69004-03-1)

Guidance literature:

With sodium methylate; In water;

upstream raw materials:

N-methyl-N'-[3-methyl-4-[4-[(trifluoromethyl)thio]phenoxy]phenyl] imidodicarbonic diamide

Diethyl carbonate

3-methyl-1-[3-methyl-4-(4-(trifluoromethylsulfanyl)phenoxy)phenyl]biuret

3-methyl-4-{4-[(trifluoromethyl)sulfanyl]phenoxy}aniline

Refernces

The Synthesis of (1,3,4-Oxadiazol-2-yl)Acrylic Acid Derivatives with Antibacterial and Protistocidal Activities

10.1134/S1068162018010132

The research aims to synthesize and study a series of new 1,3,4-oxadiazol-2-yl-acrylic acids for their potential antibacterial and protistocidal properties. The study was prompted by the need for new agents against protozoa, which rapidly develop resistance to existing drugs, and the recognition that compounds bearing an acrylic acid residue and a heterocyclic fragment could exhibit enhanced biological activity. Key chemicals used in the synthesis include maleic anhydride, various hydrazides, and POCl3. The synthesized compounds were tested for their biological activity against Staphylococcus aureus, Escherichia coli, and the protozoa Colpoda steinii. The results showed that p-substituted benzyl derivatives in the Z-form exhibited high protistocidal activity, surpassing the reference drug Baycox (toltrazuril) by several times. Notably, the 3-hydroxy-2-naphthyl derivative (IVj) demonstrated both very high protistocidal activity and moderate antibacterial activity. The study concludes that the search for antiprotozoal compounds within this class, especially Z-isomers, is promising, and these derivatives could serve as a basis for developing new pharmaceuticals with improved efficacy against both bacterial and protozoal infections.