Matches in DBpedia 2015-10 for { <http://dbpedia.org/resource/Tienilic_acid> ?p ?o }
- Tienilic_acid abstract "Tienilic acid (INN and BAN) or ticrynafen (USAN) is a loop diuretic drug with uric acid-lowering (uricosuric) action, formerly marketed for the treatment of hypertension. It was approved by FDA on May 2, 1979, and withdrawn in 1982, after case reports in the United States indicated a link between the use of ticrynafen and hepatitis.Criminal charges were brought against SmithKline executives with regard to hiding data related to toxicity while gaining FDA approval. The company pleaded guilty to 14 counts of failure to report adverse reactions and 20 counts of selling a misbranded drug.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 sulfoxide restored the thiophene ring and resulted in tienilic acid being covalently linked to the enzyme, thus inhibiting the enzyme irreversibly.The above explanation is a hypothesis. It is still not known (after 15 years) if the reactive intermediate which inactivates the CYP2C9 is the thiophene sulfoxide or the thiophene epoxide. The target on the protein is also not known (could be multiple). However tienilic acid is a good mechanism based inhibitor of CYP2C9 and seems to inactivate it stoichiometrically. Progress in proteomics may one day give the answer.Recent studies indicate that in fact the primary metabolite of tienilic acid (5-OH tienilic acid) cannot be derived from a thiophene-S-oxide intermediate as was previously hypothesized. It was determined to be derived from a thiophene epoxide intermediate and this reactive intermediate is then likely a cause for the covalent binding to as well as mechanism-based inactivation of CYP2C9.".
- Tienilic_acid atcPrefix "C03".
- Tienilic_acid atcSuffix "CC02".
- Tienilic_acid casNumber "40180-04-9".
- Tienilic_acid chEBI "9590".
- Tienilic_acid fdaUniiCode "HC95205SY4".
- Tienilic_acid iupacName "[2,3-dichloro-4-(2-thienylcarbonyl)phenoxy]acetic acid".
- Tienilic_acid pubchem "38409".
- Tienilic_acid thumbnail Tienilic_acid.svg?width=300.
- Tienilic_acid wikiPageID "1908660".
- Tienilic_acid wikiPageLength "5578".
- Tienilic_acid wikiPageOutDegree "25".
- Tienilic_acid wikiPageRevisionID "678168305".
- Tienilic_acid wikiPageWikiLink British_Approved_Name.
- Tienilic_acid wikiPageWikiLink Category:Abandoned_drugs.
- Tienilic_acid wikiPageWikiLink Category:Acetic_acids.
- Tienilic_acid wikiPageWikiLink Category:Chloroarenes.
- Tienilic_acid wikiPageWikiLink Category:Diuretics.
- Tienilic_acid wikiPageWikiLink Category:Phenol_ethers.
- Tienilic_acid wikiPageWikiLink Category:Thiophenes.
- Tienilic_acid wikiPageWikiLink Category:Withdrawn_drugs.
- Tienilic_acid wikiPageWikiLink Cytochrome_P450.
- Tienilic_acid wikiPageWikiLink Electrophile.
- Tienilic_acid wikiPageWikiLink Electrophilic.
- Tienilic_acid wikiPageWikiLink Hepatitis.
- Tienilic_acid wikiPageWikiLink Hypertension.
- Tienilic_acid wikiPageWikiLink International_Nonproprietary_Name.
- Tienilic_acid wikiPageWikiLink Kidney.
- Tienilic_acid wikiPageWikiLink Liver.
- Tienilic_acid wikiPageWikiLink Loop_diuretic.
- Tienilic_acid wikiPageWikiLink Michael_reaction.
- Tienilic_acid wikiPageWikiLink Misbranded_drug.
- Tienilic_acid wikiPageWikiLink Smith,_Kline_&_French.
- Tienilic_acid wikiPageWikiLink Sulfoxide.
- Tienilic_acid wikiPageWikiLink Thiol.
- Tienilic_acid wikiPageWikiLink Thiophene.
- Tienilic_acid wikiPageWikiLink United_States.
- Tienilic_acid wikiPageWikiLink United_States_Adopted_Name.
- Tienilic_acid wikiPageWikiLink Uric_acid.
- Tienilic_acid wikiPageWikiLinkText "Tienilic acid".
- Tienilic_acid wikiPageWikiLinkText "tienilic acid".
- Tienilic_acid atcPrefix "3.0".
- Tienilic_acid atcSuffix "CC02".
- Tienilic_acid c "13".
- Tienilic_acid casNumber "40180".
- Tienilic_acid chebi "9590".
- Tienilic_acid chembl "267744".
- Tienilic_acid chemspiderid "35204".
- Tienilic_acid cl "2".
- Tienilic_acid eliminationHalfLife "21600.0".
- Tienilic_acid excretion "Renal and biliary".
- Tienilic_acid h "8".
- Tienilic_acid hasPhotoCollection Tienilic_acid.
- Tienilic_acid inchi "1".
- Tienilic_acid inchikey "AGHANLSBXUWXTB-UHFFFAOYAF".
- Tienilic_acid iupacName "[2,3-dichloro-4-phenoxy]acetic acid".
- Tienilic_acid kegg "D02386".
- Tienilic_acid legalStatus "Withdrawn".
- Tienilic_acid metabolism Liver.
- Tienilic_acid molecularWeight "331.17".
- Tienilic_acid o "4".
- Tienilic_acid proteinBound "95.0".
- Tienilic_acid pubchem "38409".
- Tienilic_acid routesOfAdministration "Oral".
- Tienilic_acid s "1".
- Tienilic_acid smiles "C1=CSCCC2=CCl".
- Tienilic_acid stdinchi "1".
- Tienilic_acid stdinchikey "AGHANLSBXUWXTB-UHFFFAOYSA-N".
- Tienilic_acid unii "HC95205SY4".
- Tienilic_acid wikiPageUsesTemplate Template:Diuretics.
- Tienilic_acid wikiPageUsesTemplate Template:Drugbox.
- Tienilic_acid wikiPageUsesTemplate Template:Reflist.
- Tienilic_acid subject Category:Abandoned_drugs.
- Tienilic_acid subject Category:Acetic_acids.
- Tienilic_acid subject Category:Chloroarenes.
- Tienilic_acid subject Category:Diuretics.
- Tienilic_acid subject Category:Phenol_ethers.
- Tienilic_acid subject Category:Thiophenes.
- Tienilic_acid subject Category:Withdrawn_drugs.
- Tienilic_acid hypernym Drug.
- Tienilic_acid type Agent.
- Tienilic_acid type Article.
- Tienilic_acid type ChemicalSubstance.
- Tienilic_acid type Drug.
- Tienilic_acid type Agent.
- Tienilic_acid type Article.
- Tienilic_acid type Chemical.
- Tienilic_acid type Diuretic.
- Tienilic_acid type Drug.
- Tienilic_acid type Ether.
- Tienilic_acid type Heterocycle.
- Tienilic_acid type Organohalide.
- Tienilic_acid type Organohalide.
- Tienilic_acid type ChemicalObject.
- Tienilic_acid type Thing.
- Tienilic_acid type Q8386.
- Tienilic_acid comment "Tienilic acid (INN and BAN) or ticrynafen (USAN) is a loop diuretic drug with uric acid-lowering (uricosuric) action, formerly marketed for the treatment of hypertension. It was approved by FDA on May 2, 1979, and withdrawn in 1982, after case reports in the United States indicated a link between the use of ticrynafen and hepatitis.Criminal charges were brought against SmithKline executives with regard to hiding data related to toxicity while gaining FDA approval.".
- Tienilic_acid label "Tienilic acid".
- Tienilic_acid sameAs m.065f0j.
- Tienilic_acid sameAs Tienilinska_kiselina.