ALPHA-METHYL-P-[1-OXO-2-ISOINDOLINYL]-BENZENEACETIC ACID Property

Melting point:

213-214°

Boiling point:

423.97°C (rough estimate)

Density 

1.1302 (rough estimate)

refractive index 

1.4500 (estimate)

storage temp. 

2-8°C

solubility 

Methanol (Slightly, Sonicated)

form 

Solid

pka

pKa 5.8 (Uncertain)

color 

White to off-white

Safety

Hazard Codes 

T

Risk Statements 

25-40

Safety Statements 

22-36/37/39-45

RIDADR 

UN 2811 6.1 / PGIII

WGK Germany 

3

RTECS 

MU6645000

Toxicity

LD50 in rats (mg/kg): 58.66 i.v.; 60.83 orally (Buttinoni)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H351Suspected of causing cancer

Precautionary statements

P201Obtain special instructions before use.

ALPHA-METHYL-P-[1-OXO-2-ISOINDOLINYL]-BENZENEACETIC ACID Chemical Properties,Usage,Production

Chemical Properties

ALPHA-METHYL-P-[1-OXO-2-ISOINDOLINYL]-BENZENEACETIC ACID is Off-White Solid

Originator

Flosint,Carlo Erba,Italy,1976

Uses

ALPHA-METHYL-P-[1-OXO-2-ISOINDOLINYL]-BENZENEACETIC ACID is a non-steroidal anti-inflammatory agent used for treatment of pain and inflammation

Uses

analgesic, antiinflammatory

Definition

ChEBI: A monocarboxylic acid that is propionic acid in which one of the hydrogens at position 2 is substituted by a 4-(1-oxo-1,3-dihydroisoindol-2-yl)phenyl group. Initially used as an anti-inflammatory and analgesic, it was withdrawn from the market due to causi g severe gastrointestinal bleeding. It has been subsequently found to increase production of the survival motor neuron protein.

Manufacturing Process

The mixture of 7.9 g of ethyl α-(4-aminophenyl)propionate and 8.3 g of ethyl 2-chloromethylbenzoate is refluxed under nitrogen for one hour. The residue is recrystallized from hexane, to yield the ethyl α-[4-(1-oxo-isoindolino)-phenyl]- propionate of the formulamelting at 104° to 106°C. The mixture of 4.5 g thereof, 1.6 g of potassiumhydroxide, 2 ml of water and 250 ml of ethanol is refluxed under nitrogen for 2 hours and evaporated under reduced pressure. The residue is taken up in water, the solution washed with chloroform, acidified with hydrochloric acid and extracted with ethyl acetate. The extract is dried, evaporated and the residue recrystallized from ethyl acetate, to yield the corresponding free acid melting at 208° to 210°C. (Procedure reported in US Patent 3,767,805.)

brand name

Endyne;Fenint;Flogosan;Flosine;Flosyn;K 4277;Miantor.

Therapeutic Function

Antiinflammatory

World Health Organization (WHO)

Indoprofen, a nonsteroidal anti-inflammatory agent, was introduced in 1976 for the treatment of rheumatic disorders. By 1983 its use had been associated with serious adverse effects, some of which were fatal. This led to its withdrawal in the United Kingdom and Cyprus. In 1984 reports of intestinal tumours in rats led to the drug's temporary withdrawal in Germany and Italy. This was followed immediately by the suspension of marketing worldwide by the major manufacturer.