Ticrynafen

Identification

Name
Ticrynafen
Accession Number
DB04831
Type
Small Molecule
Groups
Withdrawn
Description

Ticrynafen, or tienilic acid, 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 It was withdrawn in 1982, shortly after its introduction to the market, after case reports in the United States indicated a link between the use of ticrynafen and hepatitis. (Manier et al., 1982)

Structure
Thumb
Synonyms
  • (2,3-Dichloro-4-(2-thenoyl)phenoxy)acetic acid
  • (2,3-Dichloro-4-(2-thienylcarbonyl)phenoxy)acetic acid
  • (2,3-Dichloro-4-(2-thiophenecarbonyl)phenoxy)acetic acid
  • 4-(2-Theonyl)-2,3-dichlorphenoxyessigsaeure
  • 4-(2-Thienylketo)-2,3-dichlorophenoxyacetic acid
  • Acide tienilique
  • Acido tienilico
  • Acidum tienilicum
  • Thienylic acid
  • Tienilic acid
  • Tienilico acido
International/Other Brands
Diflurex / Selacryn / Ticrex
Categories
UNII
HC95205SY4
CAS number
40180-04-9
Weight
Average: 331.171
Monoisotopic: 329.952034848
Chemical Formula
C13H8Cl2O4S
InChI Key
AGHANLSBXUWXTB-UHFFFAOYSA-N
InChI
InChI=1S/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)
IUPAC Name
2-[2,3-dichloro-4-(thiophene-2-carbonyl)phenoxy]acetic acid
SMILES
OC(=O)COC1=C(Cl)C(Cl)=C(C=C1)C(=O)C1=CC=CS1

Pharmacology

Indication

For the treatment of hypertension.

Pharmacodynamics
Not Available
Mechanism of action
Not Available
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Ticrynafen.
AcebutololAcebutolol may increase the hypotensive activities of Ticrynafen.
AcemetacinThe therapeutic efficacy of Ticrynafen can be decreased when used in combination with Acemetacin.
Acetylsalicylic acidThe therapeutic efficacy of Ticrynafen can be decreased when used in combination with Acetylsalicylic acid.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Ticrynafen.
AlfuzosinAlfuzosin may increase the hypotensive activities of Ticrynafen.
AliskirenTicrynafen may increase the hypotensive activities of Aliskiren.
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Ticrynafen.
AlphaprodineThe risk or severity of adverse effects can be increased when Alphaprodine is combined with Ticrynafen.
AlprenololAlprenolol may increase the hypotensive activities of Ticrynafen.
Food Interactions
Not Available

References

Synthesis Reference

Harold Graboyes, "Method for preparing ticrynafen." U.S. Patent US4107179, issued April, 1977.

US4107179
General References
  1. Manier JW, Chang WW, Kirchner JP, Beltaos E: Hepatotoxicity associated with ticrynafen--a uricosuric diuretic. Am J Gastroenterol. 1982 Jun;77(6):401-4. [PubMed:7091125]
External Links
KEGG Drug
D02386
KEGG Compound
C11702
PubChem Compound
38409
PubChem Substance
46505485
ChemSpider
35204
BindingDB
50090674
ChEBI
9590
ChEMBL
CHEMBL267744
Wikipedia
Ticrynafen
ATC Codes
C03CC02 — Tienilic acid

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)149 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.00254 mg/mLALOGPS
logP4.09ALOGPS
logP3.87ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)3.22ChemAxon
pKa (Strongest Basic)-5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity75.68 m3·mol-1ChemAxon
Polarizability30.45 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.913
Blood Brain Barrier+0.8914
Caco-2 permeable-0.5564
P-glycoprotein substrateNon-substrate0.6678
P-glycoprotein inhibitor INon-inhibitor0.8785
P-glycoprotein inhibitor IINon-inhibitor0.9398
Renal organic cation transporterNon-inhibitor0.875
CYP450 2C9 substrateNon-substrate0.7168
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6863
CYP450 1A2 substrateNon-inhibitor0.5326
CYP450 2C9 inhibitorNon-inhibitor0.6725
CYP450 2D6 inhibitorNon-inhibitor0.908
CYP450 2C19 inhibitorNon-inhibitor0.8257
CYP450 3A4 inhibitorNon-inhibitor0.9104
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.638
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8764
BiodegradationNot ready biodegradable0.5809
Rat acute toxicity2.5618 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9848
hERG inhibition (predictor II)Non-inhibitor0.9193
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Aryl-phenylketones
Alternative Parents
Chlorophenoxyacetates / Thiophene carboxylic acids and derivatives / Phenoxy compounds / Phenol ethers / Dichlorobenzenes / Benzoyl derivatives / Alkyl aryl ethers / Aryl chlorides / Vinylogous halides / Heteroaromatic compounds
show 5 more
Substituents
Aryl-phenylketone / Chlorophenoxyacetate / Phenoxyacetate / Phenoxy compound / 1,2-dichlorobenzene / Benzoyl / Phenol ether / Thiophene carboxylic acid or derivatives / Alkyl aryl ether / Halobenzene
show 18 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, monocarboxylic acid, thiophenes, dichlorobenzene, aromatic ketone (CHEBI:9590)

Enzymes

Details
1. Cytochrome P450 2C9
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Hutzler JM, Balogh LM, Zientek M, Kumar V, Tracy TS: Mechanism-based inactivation of cytochrome P450 2C9 by tienilic acid and (+/-)-suprofen: a comparison of kinetics and probe substrate selection. Drug Metab Dispos. 2009 Jan;37(1):59-65. doi: 10.1124/dmd.108.023358. Epub 2008 Oct 6. [PubMed:18838506]

Drug created on September 11, 2007 14:55 / Updated on August 02, 2018 05:27