azapropazone Chemical Properties

Melting point:

228°

Boiling point:

441.59°C (rough estimate)

Density 

1.0975 (rough estimate)

refractive index 

1.6000 (estimate)

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

8.66±0.20(Predicted)

Water Solubility 

147.2mg/L(35 ºC)

Safety Information

Toxicity

LD50 orl-rat: 1800 mg/kg OYYAA2 15,41,78

azapropazone Usage And Synthesis

Description

Apazone is a complex pyrazolidinedione used at 600 ~ 1200 mg/d to achieve an anti-inflammatory effect comparable to phenylbutazone. It is tightly bound to plasma protein and may displace anticoagulants and hypoglycemic agents. Its plasma half-life is 8 ~ 12 h. It is well tolerated with only a low incidence of gastric disturbances. As with all pyrazolone derivatives, the potential for bone marrow suppression exists and careful monitoring of the patient's hematologic state is recommended.

Chemical Properties

Nearly colorless, crystalline solid.

Originator

Prolixan,Siegfried,W. Germany,1970

Uses

Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.

Uses

An anti-inflammatory, analgesic, and antipyretic. It is also useful in the treatment of gout due to its uricosuric actions.

Definition

ChEBI: A member of the class of benzotriazines that is 1,2-dihydro-1,2,4-benzotriazine bearing a dimethylamino substitutent at position 3 and a methyl substituent at position 7 and in which the nitrogens at positions 1 and 2 are both acylated by a carboxy group o propylmalonic acid.

Manufacturing Process

The following describes two alternatives for the synthesis of the closely related butyl analog.
Alternative (a): In a three-neck flask with descending condenser to 3.8 grams of 3-dimethylamino-(1,2-dihydro-1,2,4-benzotriazine) are added 0.52 gram metallic sodium, dissolved in a small volume of absolute alcohol, 4.5 g of diethylbutylmalonate (diethylpropylmalonate for Apazone) and 15 ml of xylene, in a nitrogen atmosphere. The mixture is heated for 2 hours to 70°C, then for 3 hours to 110-130°C and for one more hour to 150°C, slowly distilling off the alcohol and most of the xylene. To the resulting light brown colored mass are added 200 ml of water. The resulting solution is extracted twice with ether or benzene and afterwards acidified with HCl. Yield 3.6 g of 1,2-butylmalonyl-3-dimethylamino-(1,2-dihydro-1,2,4-benzotriazine). After crystallization from alcohol the melting point is 189-190°C.
Alternative (b): 3-Dimethylamino-1,2,4-benzotriazine oxide is shaken in the presence of Raney nickel in 15 volume parts of an alcohol-acetic acid (9:1) mixture in a hydrogen atmosphere. The mixture absorbs 2 mols hydrogen per 1 mol starting material. Hydrogenation can also be effected using a palladium catalyst with a suitable solvent. After reduction it is filtered on a Buchnerfunnel through a Hyflow-layer and the solvent is evaporated in vacuum under nitrogen. The residue is dissolved in 20 parts of water-free dioxane and treated at 60°C with the calculated amount of butylmalonyl chloride (propyl malonyl chloride for Apazone) (1 mol/mol) and triethylamine (2 mol/mol). The separated triethylamine hydrochloride is filtered, the dioxane-solution is evaporated under vacuum to dryness, and the residue is dissolved in 7 volume parts of boiling acetic acid. After cooling, the product separates in lightly yellowish crystals. They are dissolved in the calculated amount of 0.25 N NaOH, treated with a small amount of carbon and precipitated with HCl. Melting point of the purified product is 187°C. Yield: approximately 60% of the theoretical amount.

brand name

Ahr 3018;Azapren;Cinnamin;Cinnopropazone;Dolo-prolixan;Pentosol;Prodisan;Prolixana;Sinnamin;Tolyprina;Xani.

Therapeutic Function

Antiarthritic

World Health Organization (WHO)

Azapropazone, which has anti-inflammatory, analgesic and antipyretic activity, was introduced in 1970 for the treatment of rheumatic disorders. Although sometimes classified as a pyrazolone derivative, the relationship with this group of compounds has been disputed and classification as a benzotriazine derivative might be preferable. Although, to date, it has not been associated with blood dyscrasias, some regulatory authorities have applied the same rigorous restrictions to its indications as they have applied to pyrazolone derivatives. The World Health Organization was informed that as of December 1987 azapropazone was available in some 27 countries.

Hazard

Nausea, vomiting, abdominal pain, gastric ulcers; moderately toxic.

Safety Profile

Moderately toxic by ingestion,intraperitoneal and intravenous routes. When heated todecomposition it emits toxic fumes of NOx.

Synthesis

Synthesis: a mixture of 1,2-dihydro-3-dimethylamino-7-methylbenzotriazine, diethyl propylmalonate, and sodium ethoxide in xylene is heated over a period of time to 150 ?C, cooled, and acidified to give the desired product.

azapropazone (13539-59-8)Related Product Information

• azapropazone
• N-PHENYL-N'-PROPIONYLHYDRAZINE
• N-(2-aminophenyl)-2-methylpropanamide
• 1-Phenyl-4-methyl-3-pyrazolidone
• Phenidone
• 1-Pyrazolidinecarboximidamide,N-methyl-
• 6-hydroxyazapropazone