Identification

Name
Phenolphthalein
Accession Number
DB04824
Type
Small Molecule
Groups
Withdrawn
Description

Phenolphthalein was withdrawn in Canada due to concerns with carcinogenicity in 1997.

Structure
Thumb
Synonyms
  • 3,3-Bis(4-hydroxyphenyl)phthalide
  • Fenolftalein
  • Fenolftaleina
  • Phenolphtaleine
  • Phenolphthaleinum
  • Phthalimetten
  • phthalin
  • Yellow phenolphthalein
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Alophen Tab 60mgTablet60 mgOralWarner Lambert Canada Inc.1992-12-311997-10-10Canada
Espotabs Laxative Tablets 90mgTablet90 mgOralCombe Incorporated1994-12-311997-07-24Canada
EX-lax Chocolated Tab 95mgTablet95 mgOralNovartis1991-12-311997-10-10Canada
Feen-A-mint Phenolphthalein Tab 100mgTablet100 mgOralSchering Plough Healthcare Products Canada, A Division Of Schering Canada Inc.1993-12-311997-08-08Canada
Laxative Pills - TabletTablet90 mgOralStanley Pharmaceuticals, A Division Of Vita Health Products Inc.1996-12-311997-08-08Canada
Laxative TabletsTablet94 mgOralPerrigo International1995-12-311997-10-16Canada
Neo Prunex JamJelly100 mgOralNeolab Inc1982-12-311997-08-12Canada
International/Other Brands
Agoral / Alophen / Chocolax / Colax / Doxan / Doxidan / Espotabs / Euchessina / Evac-q-kit / Evac-q-kwik / Evac-q-tabs / Evac-u-gen / Evac-v-lax / Ex-lax / Feen-a-mint gum / Feen-a-mint laxative mints / Femilax / Koprol / Lax-pills / Laxcaps / Laxin / Laxogen / LILO / Medilax / Phenolax / Phillips gelcaps / Prulet / Purga / Purgen / Purgophen / Spulmako-lax / Trilax
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Agarol Eml StrawberryPhenolphthalein (65 mg) + Glycerin (200 mg) + Mineral oil (1.6 ml)EmulsionOralWarner Lambert Canada Inc.1992-12-311997-09-15Canada
Agarol Vanilla Laxative LiqPhenolphthalein (65 mg) + Glycerin (200 mg) + Mineral oil (1.6 ml)LiquidOralWarner Lambert Canada Inc.1992-12-311997-09-15Canada
Calcium Docuphen CapPhenolphthalein (65 mg) + Docusate calcium (60 mg)CapsuleOralPharmascience Inc1988-12-311997-10-10Canada
Correctol Laxative TabPhenolphthalein (65 mg) + Docusate sodium (100 mg)TabletOralSchering Plough Healthcare Products Canada, A Division Of Schering Canada Inc.1971-12-311997-08-08Canada
Doxidan CapsulesPhenolphthalein (65 mg) + Docusate calcium (60 mg)CapsuleOralHoechst Roussel Canada Inc.1994-12-311998-08-12Canada
Doxidan CapsulesPhenolphthalein (65 mg) + Docusate calcium (60 mg)CapsuleOralHoechst Canada Inc.1987-12-311997-08-05Canada
Doxidan CapsulesPhenolphthalein (65 mg) + Docusate calcium (60 mg)CapsuleOralHoechst Marion Roussel1997-04-211997-10-10Canada
EX-lax Light Formula Lax W Stool Soften TabPhenolphthalein (65 mg) + Docusate sodium (75 mg)TabletOralNovartis1991-12-311997-10-10Canada
LaxarolPhenolphthalein (65 mg) + Mineral oil (1.6 ml)LiquidOralTherapex Division De E Z Em Canada Inc1985-12-311997-07-22Canada
Mucinum TabPhenolphthalein (75 mg) + Sennosides (40 mg)TabletOralSabex Inc1978-12-311997-10-10Canada
Categories
UNII
6QK969R2IF
CAS number
77-09-8
Weight
Average: 318.3228
Monoisotopic: 318.089208936
Chemical Formula
C20H14O4
InChI Key
KJFMBFZCATUALV-UHFFFAOYSA-N
InChI
InChI=1S/C20H14O4/c21-15-9-5-13(6-10-15)20(14-7-11-16(22)12-8-14)18-4-2-1-3-17(18)19(23)24-20/h1-12,21-22H
IUPAC Name
3,3-bis(4-hydroxyphenyl)-1,3-dihydro-2-benzofuran-1-one
SMILES
OC1=CC=C(C=C1)C1(OC(=O)C2=CC=CC=C12)C1=CC=C(O)C=C1

Pharmacology

Indication

Used for over a century as a laxative.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UUDP-glucuronosyltransferase 1-9Not AvailableHuman
UNuclear receptor subfamily 1 group I member 2Not AvailableHuman
UNuclear receptor subfamily 1 group I member 3Not AvailableHuman
UEstrogen receptor alpha
agonist
Human
USex hormone-binding globulinNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
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
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Hershel B. Prindle, George E. Ham, "Preparation of phenolphthalein using cation exchange resins and aryl phosphites." U.S. Patent US4252725, issued March, 1966.

US4252725
General References
Not Available
External Links
KEGG Drug
D05456
KEGG Compound
C14286
PubChem Compound
4764
PubChem Substance
46506108
ChemSpider
4600
BindingDB
50077844
ChEBI
34914
ChEMBL
CHEMBL63857
PharmGKB
PA450915
Wikipedia
Phenolphthalein
ATC Codes
A06AB04 — Phenolphthalein

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
EmulsionOral
TabletOral60 mg
TabletOral95 mg
TabletOral100 mg
LiquidOral
TabletOral90 mg
TabletOral94 mg
TabletOral
JellyOral100 mg
CapsuleOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)262.5 °CPhysProp
water solubility400 mg/LYALKOWSKY,SH & HE,Y (2003)
logP2.41HANSCH,C ET AL. (1995), pH 7.4
pKa9.7 (at 25 °C)MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.00992 mg/mLALOGPS
logP4.41ALOGPS
logP4.35ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)9.16ChemAxon
pKa (Strongest Basic)-6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.76 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity91.04 m3·mol-1ChemAxon
Polarizability32.65 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9934
Blood Brain Barrier+0.81
Caco-2 permeable-0.6464
P-glycoprotein substrateNon-substrate0.5296
P-glycoprotein inhibitor INon-inhibitor0.9622
P-glycoprotein inhibitor IINon-inhibitor0.7602
Renal organic cation transporterNon-inhibitor0.8906
CYP450 2C9 substrateNon-substrate0.7388
CYP450 2D6 substrateNon-substrate0.8969
CYP450 3A4 substrateNon-substrate0.6225
CYP450 1A2 substrateNon-inhibitor0.778
CYP450 2C9 inhibitorInhibitor0.6684
CYP450 2D6 inhibitorNon-inhibitor0.8938
CYP450 2C19 inhibitorNon-inhibitor0.7654
CYP450 3A4 inhibitorNon-inhibitor0.5773
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5636
Ames testNon AMES toxic0.9267
CarcinogenicityNon-carcinogens0.9093
BiodegradationNot ready biodegradable0.9381
Rat acute toxicity2.3649 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9899
hERG inhibition (predictor II)Non-inhibitor0.876
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (10.4 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Mass Spectrum (Electron Ionization)MSsplash10-00fr-2690000000-8c929a0403799e4cd208
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-2950000000-2239a8a809fdd9396eaf
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzofuranones. These are organic compounds containing a benzene ring fused to a furanone.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzofurans
Sub Class
Benzofuranones
Direct Parent
Benzofuranones
Alternative Parents
Phthalides / 1-hydroxy-2-unsubstituted benzenoids / Benzene and substituted derivatives / Lactones / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Benzofuranone / Phthalide / Isobenzofuranone / Isocoumaran / Phenol / 1-hydroxy-2-unsubstituted benzenoid / Benzenoid / Monocyclic benzene moiety / Lactone / Carboxylic acid ester
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenols (CHEBI:34914)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Uesawa Y, Staines AG, Lockley D, Mohri K, Burchell B: Identification of the human liver UDP-glucuronosyltransferase involved in the metabolism of p-ethoxyphenylurea (dulcin). Arch Toxicol. 2007 Mar;81(3):163-8. Epub 2006 Aug 5. [PubMed:16897040]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [PubMed:20869355]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital re...
Gene Name
NR1I3
Uniprot ID
Q14994
Uniprot Name
Nuclear receptor subfamily 1 group I member 3
Molecular Weight
39942.145 Da
References
  1. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [PubMed:20869355]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Ravdin PM, van Beurden M, Jordan VC: Estrogenic effects of phenolphthalein on human breast cancer cells in vitro. Breast Cancer Res Treat. 1987;9(2):151-4. [PubMed:3620717]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [PubMed:25349334]

Drug created on September 11, 2007 14:27 / Updated on December 01, 2017 15:33