FENTIAZAC

Originator

Norvedan,LPB,Italy,1975

The Uses of FENTIAZAC

Anti-inflammatory.

Definition

ChEBI: 2-[4-(4-chlorophenyl)-2-phenyl-5-thiazolyl]acetic acid is a member of thiazoles.

Manufacturing Process

13.6 g methyl 3-(p-chlorobenzoyl)-3-bromopropionate in 30 ml methanol are added to a solution of 5.6 g potassium thioacetate in 30 ml methanol. Immediate precipitation of KBr is observed. The suspension is refluxed for 10 minutes.
It is cooled to ambient temperature, filtered, and the methanol is evaporated to dryness. 13.2 g methyl 3-(p-chlorobenzoyl)-3-thioacetylpropionate in the form of a chromatographically pure orange-colored oil are obtained.
A suspension of 13.2 g methyl 3-(p-chlorobenzoyl)-3-thioacetylpropionate is agitated in 500 ml of a 2 N aqueous solution of KOH for 6 hours at ambient temperature in an atmosphere of nitrogen, followed by extraction with ethyl ether. The aqueous phase, adjusted to a pH equal to 2 with 2N HCl, is extracted with ethyl ether which was washed with water, dried over Na2SO4, and finally evaporated to dryness
9.8 g of crude 3-(p-chlorobenzoyl)-3-mercaptopropionic acid are obtained. By recrystallizing from isopropyl ether there are obtained 8.6 g of pure product, MP 96°C to 97°C (yield: 79%).
1.7 ml benzonitrile and 5.05 ml diethylamine are added to a solution of 4 g 3- (p-chlorobenzoyl)-3-thiol-propionic acid in 50 ml ethanol. The solution is agitated at ambient temperature for 60 minutes in an atmosphere of nitrogen. It is then evaporated to a syrupy consistency and 60 ml 50% aqueous acetic acid are added, whereupon the mixture is refluxed for 60 minutes. It is evaporated to a small volume, adjusted to a pH equal to 8 with a saturated solution of sodium bicarbonate and then extracted with ethyl ether. The aqueous phase is acidified with 2N HCl (Congo red), and then again extracted with ethyl ether. It is dried over Na2SO4 and evaporated to dryness. The evaporation residue is recrystallized from benzene and 4 g 4-(p-chlorophenyl)- 2-phenyl-thiazol-5-yl-acetic acid are obtained (MP = 152°C to 154°C, yield - 74.3%).

Therapeutic Function

Analgesic, Antipyretic, Antiinflammatory

General Description

Fentiazac is reported to have anti-inflammatory, analgesic, and antipyretic activity. It has been given once or twice a day at levels between 100 and 200 mg/dose in the treatment of postoperative pain, including that following orthopedic surgery. The most common adverse effect is gastrointestinal intolerance, including epigastric pain, nausea, and vomiting. Effects on the CNS, such as headache and dizziness, also have been reported.

Trade name

Atilan (Zambon, Brazil), Donorest (Fontoura-Wyeth, Brazil), Flogene (Polifarma, Italy), Norvedan (Boehringer Mannheim, Austria; LPB, Italy).

Synthesis

Synthesis: refluxing a mixture of 3-bromo- 3-(4-chlorobenzoyl)propionic acid and thiobenzamide in ethanol gives ethyl 2-phenyl-4-(4- chlorophenyl)thiazole-5-acetate, which is then saponified to yield fentiazac.