40180-04-9

Usage

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 In 1991, it was eventually also withdrawn there since cases of hepatitis, some of which were fulminant, had continued to occur.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.

InChI:InChI=1/C13H8Cl2O4S/c14-11-7(13(18)9-2-1-5-20-9)3-4-8(12(11)15)19-6-10(16)17/h1-5H,6H2,(H,16,17)

Downstream Products

• 55901-78-5 [2,3-dichloro-4-(hydroxy-thiophen-2-yl-methyl)-phenoxy]-acetic acid 

Relevant academic research and scientific papers

Novel diuretics

An advantageous diuretic action by excretion of water, sodium and chloride ions, with reduced excretion of potassium ions, is effected by combined administration of a 19-oxygenated steroid compound of the pregnane series of the formula STR1 wherein Ra represents a hydrogen atom, and Rb represents an α-oriented lower alkanoylthio group, or Ra and Rb together represent a carbon-carbon bond or an α- or β-oriented methylene radical, R represents a free hydroxymethyl group or a hydroxymethyl group etherified by a lower alkyl or esterified by a lower alkanoyl; or represents a carboxyl group or a lower alkoxycarbonyl group, and R2 represents a hydrogen atom or the acyl radical Ac of a carboxylic acid, as the aldosterone-antagonising component A on the one hand, and, on the other hand, of a conventional diuretic which is unspecific in respect of electrolyte excretion, e.g. a diuretically effective derivative of benzothiadiazine, benzenesulfonamide, phenoxyacetic acid, benzofuran-2-carboxylic acid or 2,3-dihydrobenzofuran-2-carboxylic acid, as component B. The two components A and B can be administered separately or together as an appropriate composition or pharmaceutical preparation.

(2,3-Dichloro-4-carboxy)phenoxy acetic acid and esters thereof

2,3-Dichloro-4-(2-thenoyl)phenoxyacetic acid (tienilic acid) is prepared by reacting (2,3-dichloro-4-carboxy)phenoxyacetic acid with thiophene in the presence of a dehydration agent. The (2,3-dichloro-4-carboxy)phenoxyacetic acid is a novel compound.

Use of cyclic esters to prepare 2,3-dichloro-4-(2-thenoyl)phenoxyacetic acid

A new process and intermediates for preparing 2,3-dichloro-4-(2-thenoyl)phenoxyacetic acid (ticrynafen, a diuretic agent) using as a key reaction a Friedel-Crafts acylation of an esterified 3-(2,3-dichlorophenoxy)-1,2-propanediol using a thenoyl halide.