TICRYNAFEN Property

Melting point:

148-149oC

Boiling point:

534.6±50.0 °C(Predicted)

Density 

1.532

storage temp. 

-20°C

solubility 

DMSO: soluble5mg/mL (clear solution)

pka

2.79±0.10(Predicted)

form 

powder

color 

white to beige

Safety

Hazard Codes 

Xn

Risk Statements 

22

WGK Germany 

3

RTECS 

AG9300000

Toxicity

LD50 in mice (mg/kg): 225 i.v., 1275 orally (US 3758506)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

TICRYNAFEN Chemical Properties,Usage,Production

Description

Cytochrome P450 enzymes function to metabolize both endogenous and exogenous compounds. Both the 3A and 2C isoforms are present in human liver of which CYP2C9 seems most highly expressed. Tienilic acid is a specific suicide substrate for CYP2C9 and CYP2C10 whereby its oxidation inactivates the enzyme. The time required to inactivate one half of the CYP2C10 enzyme at the maximal rate (t_½max) is 3.4 minutes, with a dissociation constant (KI) value of 4.3 μM.

Chemical Properties

Pale Beige Solid

Uses

A heterocycloc derivative of phenoxyacetic Acid. Uses as a diuretic, uricosuric, anhtihypertensive

Uses

Tienilic Acid is a heterocyclic derivative of phenoxyacetic acid. Tienilic acid is used as diuretic, uricosuric, antihypertensive.

Definition

ChEBI: An aromatic ketone that is 2,3-dichlorophenoxyacetic acid in which the hydrogen at position 4 on the benzene ring is replaced by a thiophenecarbonyl group. A loop diuretic used to treat hypertension, it was withdrawn from the market in 1982 due to links wi h hepatitis.

brand name

Tienilic Acid is INN and BAN;Anp 3624;Diflarex;Fr 3068;Selcryn;Skf-62698;Ticrynafen;Ticrynapen.

World Health Organization (WHO)

Tienilic acid, a diuretic agent with uricosuric and antihypertensive activity, was introduced in 1976. By 1979 its use had been associated with cases of hepatic toxicity, some of which were fatal, which led to the withdrawal of the drug in most countries in which it was marketed. In France, however, precautions regarding the use of tienilic acid were issued by the Pharmacovigilance Commission and the drug remained available for another decade. In 1991, it was eventually also withdrawn there since cases of hepatitis, some of which were fulminant, had continued to occur.

Biochem/physiol Actions

Tienilic Acid (Ticrynafen) is a P450 inhibitor, a specific suicide substrate for CYP2C9 and CYP2C10. It was once used as a loop diuretic drug with uric acid-lowering (uricosuric) actvity, but was removed from market because of hepatotoxicity.