Tienilic acid

Tienilic acid

File:Tienilic acid.svg
Clinical data
Routes of administration	Oral
ATC code	C03CC02 (WHO)
Legal status
Legal status	Withdrawn
Pharmacokinetic data
Protein binding	95%
Metabolism	Hepatic
Elimination half-life	6 hours
Excretion	Renal and biliary
Identifiers
IUPAC name 2-[2,3-dichloro-4-(thiophene-2-carbonyl)phenoxy]acetic acid
CAS Number	40180-04-9
PubChem CID	38409
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C13H8Cl2O4S
Molar mass	331.17 g/mol
3D model (JSmol)	Interactive image
SMILES C1=CSC(=C1)C(=O)C2=C(C(=C(C=C2)OCC(=O)O)Cl)Cl

Tienilic acid (INN and BAN) or ticrynafen (USAN) is a diuretic drug with uric acid-lowering (uricosuric) action, formerly marketed for the treatment of hypertension. It was withdrawn in 1982, shortly after its introduction to the market, after case reports in the United States indicated a link between the use of ticrynafen and hepatitis.

Tienilic acid was found to act as a suicide substrate at the cytochrome P450 enzymes involved in drug metabolism. Unfortunately, the metabolic reaction carried out by these enzymes converted tienilic acid to a thiophene sulfoxide which proved highly electrophilic. This encouraged a Michael reaction leading to alkylation of a thiol group in the enzyme's active site. Loss of water from the thiophene sulphoxide restored the thiophene ring and resulted in tienilic acid being covalently linked to the enzyme, thus inhibiting the enzyme irreversibly.