The Role and Preparation of Tesmilifene

The Role and Preparation of Tesmilifene

Patrozuril is a triazinone anti-protozoal drug developed by Bayer for the treatment of protozoal diseases. Chinese name: Patrozuril (or Ponazuril, Toltrazuril Sulfone, Toltrazuril Sulfone, Toltrazuril Sulfone), chemical name: 1-[3-methyl-4-(4-trifluoromethanesulfonyl phenolyl)phenyl]-3-methyl-1,3,5-triazine-2,4,6-trione.
Chicken coccidiosis is a parasitic disease that seriously affects the poultry industry. For a long time, coccidiosis has been treated mainly by drugs, but long-term and irrational use of anticoccidial drugs has caused drug resistance and drug residues.
Toltrazuril is a commonly used anticoccidial drug in poultry and swine. Toltrazuril is metabolized to patrozuril in animals after administration by almost 100%, and studies have shown that patrozuril has a lower level of toxic effects than toltrazuril in animals. Patozuril (panazuril, referred to as toltrazuril sulfone when describing the metabolite in vivo) is one of the major metabolites of toltrazuril in the body and is a triazine anticoccidial drug related to toltrazuril and the potent form of toltrazuril.

Compared to toltrazuril, patozuril readily crosses the blood-brain barrier and directly kills Neospora hongi (Nhughesi) and Sarcocystis carinii in the brain and cerebrospinal fluid. Nhughesi) and Sarcocystis sneurona in the brain and cerebrospinal fluid, providing effective relief of EPM symptoms. Studies have shown that patrozuril kills coccidia in animals without affecting the production of autoimmunity. With the strengthening of autoimmunity, the diseased animals can gradually get rid of their dependence on the drug. In addition, patrozuril can cross the placental barrier and directly kill Neospora caninum, which crosses the placenta and causes severe damage to the fetus. 2001, the FDA approved the marketing of an oral paste of patrozuril (trade name Marquis) for the treatment of equine protozoal encephalomyelitis (EPM). Currently, patoxuril has not been approved for the control of avian coccidiosis, and no studies on residual elimination of patoxuril in broiler chickens have been reported. Patrozuril has strong anticoccidial activity and does not undergo transformation in the body after absorption, which is expected to shorten the residual time in the body and develop into an anticoccidial drug for chickens.
Uses
Patoxuril was approved by the FDA in 2001 for the treatment of Neospora hughesi and Sarcocystis neurona causing central mammalian diseases such as equine protozoal encephalomyelitis (EPM).

Action
Patrozuril is the predominant metabolite of toltrazuril. Toltrazuril is almost 100% converted to patoxuril after metabolism in animals after administration, and studies have shown that patoxuril has a lower level of toxic effects than toltrazuril in animals.

Compared with previous anticoccidial drugs such as toltrazuril, the most important feature of patrozuril is that it can cross the blood-brain barrier and directly kill Neospora hughesi and Sarcocystis neurona located in the brain and cerebrospinal fluid, effectively relieving the symptoms of EPM. Studies have shown that patoxuril kills coccidia in animals without affecting the production of their own immunity. With the strengthening of autoimmunity, the diseased animals can gradually get rid of their dependence on the drug. In addition, patoxuril can also cross the placental barrier and directly kill Neospora caninum, which can cause serious damage to the fetus through the placenta.

Preparation method
CN102285927A provides a method for the preparation of a novel anticoccidial drug patoxuril, characterized by the following steps:

• 1) Preparation of 3-methyl-4-(4-trifluoromethylthiophenoxy)-nitrobenzene:
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• 2)Preparation of 3-methyl-4-(4-trifluoromethylthiophenoxy)-aniline:
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• 3)Preparation of 3-methyl-4-(4-trifluoromethylthiophenoxy)-phenylisocyanate:
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• 4) Preparation of 1-[3-methyl-4-(4-trifluoromethylthiophenoxy)-m-tolyl]-1,3,5-triazinetrione:
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• 5) Preparation of 1-[3-methyl-4-(4-trifluoromethanesulfonyl)phenoxy]-phenyl 3-methyl-1,3,5-triazine-2,4,6-trione.