Apazone

Phenacvl-6-aminopeniciilate HCI D-Phenylglycyl Chioride HCI 4-Hydroxy-1,5-naphthyridine-3-carboxyiic acid-N-succinimide ester 

The above product was dissolved in dimethylformamide (65 ml), sodium thiophenoxide (0.89 g) was added thereto, and the resultant mixture was stirred at room temperature for 1 hour. To the resultant mixture, acetone (650 ml) was added, and the separated crystals were collected by filtration and washed with acetone and ether in order to give the objective compound in the form of the sodium salt (1.3 g). 

In the above procedure, the use of 4-hydroxy-1,5-naphthyridine-3-carbonyl chloride in place of 4-hydroxy-1,5-naphthyridine-3-carboxylic acid N-succinimide ester can also afford the same objective compound as above. The use of sodium thio-n-propoxide in place of sodium thiophenoxide can also give the objective compound in the form of the sodium salt. 

Chemical Name 5-(dimethylamino)-9-methyl-2-propyl-1H-pyrazolo[1,2-a] [1,2,4]benzo-triazine-1,3(2H)-dione 

Trade Name Manufacturer Country Year Introduced 

Phenacyl-6-aminopenicillate HCI D-Phenylglycyl Chloride HCI 4-Hydro xy-1,5-naphthyridine-3-carboxylic acid-N-succinimide ester 

4-Hydroxy-1,5-naphthyridlne-3-carboxylic acid-N-succinimide ester 

6-aminopenicillanate hydrochloride (1 S5g) and D-phenylglycyl chloride hydrochloride (1.29 g) in dichloromethane (20 ml), sodium bicarbonate (1.05 g) was added, and the resultant mixture was stirred while cooling with ice for 6 hours. The reaction mixture was filtered to eliminate the by-produced sodium chloride. The filtrate was admixed with isopropanol and concentrated under reduced pressure by the aid of a rotary evaporator. After the evaporation of dichloromethane, the precipitate was collected by filtration to give the objective compound 

Yamada, H., Tobiki, H.. Nakatsuka, l.,Tanno,N.,Shimago, K. and Nakagome.T. U.S. Patent 4.005/)75 January 25,1977 assigned to Sumitomo Chemical Co., Ltd. 

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Antazoline 1, 242 Antipyrine T, 234 Apazone 475 Aprindene 208 Aprobarbital I, 268 Aprophen 1, 91 Arbaprostil ... 

Piperacillin sodium Diethyl-d -phenyl propyl) malonate Phenprocoumon Diethylpropyl malonate Apazone... 

Antisecretory activity, 2 Antitussive, 11 Antiulcer activity, 2 Apazone, 475... 

Apazone is an analgesic (pain reliever) not currently available in the United States. It is absorbed well through the G.l. tract and binds extensively to plasma proteins thereby extending its half-life (20-24 hours). Its mode of action is to inhibit prostaglandin synthetase. This, in turn, affects the pain centers and decreases the inflammatory response. 

The dioxopyrazolines are also acidic because of their enolic group (4,4-disubstituted analogues are inactive) and a recent example azapropazone (apazone) (184) inhibits prostaglandin synthesis. Its pharmacological properties are like those of phenylbutazone and it is also uricosuric. Anti-inflammatory 1,2-benzothiazine 1,1-dioxides such as piroxicam (185 R = 2-pyridyl) also have an acidic enolic group whose anion can be stabilized by... 

These drugs are available in many other countries but are not sold in the USA. Azapropazone (apazone), a pyrazolone derivative, is structurally related to phenylbutazone but appears less likely to cause agranulocytosis. Its half-life of 12-16 hours may be doubled in patients with decreased renal function. Carprofen is a propionic acid derivative with a half-life of 10-16 hours. The indications and adverse effects of azapropazone and carprofen are similar to those of other NSAIDs. 

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