Fentiazac

Therapeutic Function Analgesic, antipyretic and antiinflammatory Chemical Name 4-(p-Chlorophenyl)-2-phenyl-thiazol-5-yl-acetic acid Common Name — 

Trede Name Manufacturer Country Year Introduced 

6 g methyi 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 refiuxed for 10 minutes. 

It is cooied to ambient temperature, fiitered, and the methanol is evaporated to dryness. 13.2 g methyl 3-(p-chlorobenzoyl)-3-thioacetylpropionate in the form of a chromatographically pure orange-coiored oii are obtained. 

A suspension of 13.2 g methyi 3-(p-chiorobenzoyl)-3-thioacetylpropionate is agitated in 500 ml of a 2N aqueous solution of KOH for 6 hours at ambient temperature in an atmosphere of nitrogen, foiiowed by extraction with ethyl ether. The aqueous phase, adjusted to a pH equal to 2 with 2N HCI, is extracted with ethyl ether which was washed with water, dried over Na2S04, and finaily evaporated to dryness. 

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Fentiazac (134) is a member of the biarylacetic acid class of nonsteroidal antiinflammatory agents. Its. synthesis also involves the Hjtntzsch reaction. Tliiobcn/ainide (133) is reacted wiih 3-(4-chlorobenzoyl)-3-broinoprftpionic acid (132) to give feutiazoc (134) 46[. 

Mepenzolate bromide Pipenzolate bromide Pipoxolan HCI Benzoic anhydride Flavoxate HCI Benzonitrile Fentiazac Benzophenone Diphenidol Phenytoin 1,4-Benzoaquinone Dobesilate calcium Ethamsylate Megestrol acetate Benzotetronic acid... 

One of the two classic schemes for constructing the thiazole ring involves the condensation of a thioamide or its equivalent with an a-haloketone. The reaction can be visualized as involving, as the first step, the displacement of halogen by sulfur from the enol form of the amide imine formation will then close the ring. Thus, reaction of bromoketone (99-2) obtained from the bromination of the corresponding keto-acid with thioamide (99-1) affords thiazole (99-3) in a single step. There is thus obtained the NSAID fentiazac [109]. 

Fentiazac, a nonsteroidal anti-inflammatory drug, is a simple example. Disconnection shows that we need thiobenzamide and an easily made a-haloketone (easily made because the ketone can eno-lize on this side only—see Chapter 21). 

Suggest a synthesis of fentiazac, a nonsteroidal antiinflammatory drug. The analysis is in the chapter but you need to explain why you need these particular starting materials as well as how you wo uld make them. 

Pyrosis, epigastric pain, nausea, constipation/diarrhea, and occult bleeding are the most frequent gastrointestinal effects of fentiazac (3). Rectal administration can cause both local and systemic adverse effects. 

In one study, seven of 20 patients with rheumatoid arthritis had significant rises in aspartate transaminase and alkaline phosphatase activities (4). Reversible hepatotoxicity occurred in three of 33 patients who took fentiazac during long-term therapy (2). 

Buerklin EM, Ballard IM. A double blind comparison of fentiazac and phenylbutazone in the treatment of acute tendinitis and bursitis. Curr Med Res Opin 1979 6(Suppl 2) 90. 

Bunde B, Deckers Y, Dequeker J. Fentiazac in rheumatoid arthritis comparison with sulindac and long-term tolerance. Curr Med Res Opin 1983 8(5) 310-14. 

Teixeira MA, Da Silva AP, Lourenco I, Teixeira ML. Fentiazac in the treatment of some rheumatic disorders. Curr Med Res Opin 1979 (Suppl 2) 97-106. 

Fentiazac, a thiazoleacetic acid derivative, has the same adverse reactions profile as other NSAIDs. Adverse effects in as many as 56% of patients (5-56%), are even more frequent than with phenylbutazone (1). 

In 40 patients with rheumatoid arthritis enrolled in a double-blind trial of fentiazac 400 mg/day or sulindac 200 mg/day for 3 months, adverse effects were reported in three patients taking fentiazac (rash, headache, epigastric pain) (2). 

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