Identification

Name
Propylthiouracil
Accession Number
DB00550  (APRD00297)
Type
Small Molecule
Groups
Approved
Description

A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)

Structure
Thumb
Synonyms
  • 2-Mercapto-6-propyl-4-pyrimidone
  • 2-Mercapto-6-propylpyrimid-4-one
  • 2-Thio-4-oxo-6-propyl-1,3-pyrimidine
  • 2-Thio-6-propyl-1,3-pyrimidin-4-one
  • 2,3-dihydro-6-Propyl-2-thioxo-4(1H)-pyrimidinone
  • 4-Propyl-2-thiouracil
  • 6-Propyl-2-thio-2,4(1H,3H)pyrimidinedione
  • 6-Propyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
  • 6-Propylthiouracil
  • 6-Thio-4-propyluracil
  • Propiltiouracilo
  • Propylthiouracil
  • Propylthiouracile
  • Propylthiouracilum
External IDs
NSC-6498 / NSC-70461
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Propyl-thyracilTablet50 mgOralPaladin Labs Inc1951-12-31Not applicableCanada
Propyl-thyracilTablet100 mgOralPaladin Labs Inc1945-12-31Not applicableCanada
PropylthiouracilTablet50 mg/1OralClinical Solutions Wholsesale2010-01-292017-07-01Us
PropylthiouracilTablet50 mg/1OralAmerincan Health Packaging2015-09-15Not applicableUs
PropylthiouracilTablet50 mg/1OralDAVA Pharmaceuticals, Inc.1947-07-28Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-propylthiouracilTablet100 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-propylthiouracilTablet50 mgOralApotex CorporationNot applicableNot applicableCanada
PMS-propylthiouracilTablet100 mgOralPharmascience IncNot applicableNot applicableCanada
PMS-propylthiouracilTablet50 mgOralPharmascience IncNot applicableNot applicableCanada
PropylthiouracilTablet50 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs1973-01-09Not applicableUs
PropylthiouracilTablet50 mg/1OralRemedy Repack2013-03-202016-10-25Us
PropylthiouracilTablet50 mg/1OralAvera Mc Kennan Hospital2015-03-03Not applicableUs
PropylthiouracilTablet50 mg/1OralCardinal Health1982-01-01Not applicableUs
PropylthiouracilTablet50 mg/1OralAv Kare, Inc.1997-01-012016-02-11Us
PropylthiouracilTablet50 mg/1OralActavis Pharma Company2006-01-15Not applicableUs00228 2348 10 nlmimage10 d6476b2b
International/Other Brands
Antiroid (Bu Kwang) / Propil (Pfizer) / Propilracil (Biolab) / Propycil (Admeda) / Proracyl (Genopharm) / Prothiucil (Phafag) / Prothuril (Uni-Pharma) / PTU (Alkaloid) / Thiuragyl (Tanabe Mitsubishi Pharma) / Thyrosan (Sun-Farm) / Tiotil (Nevada Pharma) / Tirostat (Metlen) / Uracil (Pharmasant)
Categories
UNII
721M9407IY
CAS number
51-52-5
Weight
Average: 170.232
Monoisotopic: 170.051383642
Chemical Formula
C7H10N2OS
InChI Key
KNAHARQHSZJURB-UHFFFAOYSA-N
InChI
InChI=1S/C7H10N2OS/c1-2-3-5-4-6(10)9-7(11)8-5/h4H,2-3H2,1H3,(H2,8,9,10,11)
IUPAC Name
6-propyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidin-4-one
SMILES
CCCC1=CC(=O)NC(=S)N1

Pharmacology

Indication

Used to manage hyperthyroidism which is due to an overactive thyroid gland (Grave's disease).

Structured Indications
Pharmacodynamics

Propylthiouracil is a thiourea antithyroid agent. Grave's disease is the most common cause of hyperthyroidism. It is an autoimmune disease where an individual's own antibodies attach to thyroid stimulating hormone receptors within cells of the thyroid gland and then trigger overproduction of thyroid hormone. The two thyroid hormones manufactured by the thyroid gland, thyroxine (T4) and triiodothyronine (T3), are formed by combining iodine and a protein called thyroglobulin with the assistance of an enzyme called peroxidase. PTU inhibits iodine and peroxidase from their normal interactions with thyroglobulin to form T4 and T3. This action decreases thyroid hormone production. PTU also interferes with the conversion of T4 to T3, and, since T3 is more potent than T4, this also reduces the activity of thyroid hormones. The actions and use of propylthiouracil are similar to those of methimazole.

Mechanism of action

Propylthiouracil binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T4) and tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones.

TargetActionsOrganism
AThyroid peroxidase
inhibitor
Human
Absorption

Well absorbed following oral administration.

Volume of distribution
Not Available
Protein binding

82%

Metabolism
Not Available
Route of elimination

Propylthiouracil is readily absorbed and is extensively metabolized. Approximately 35% of the drug is excreted in the urine, in intact and conjugated forms, within 24 hours.

Half life

2 hours

Clearance
Not Available
Toxicity

Oral, rat: LD50 = 1250 mg/kg.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolPropylthiouracil may decrease the anticoagulant activities of Acenocoumarol.Approved
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be increased when it is combined with Propylthiouracil.Approved
AcetyldigoxinThe serum concentration of Acetyldigoxin can be increased when it is combined with Propylthiouracil.Experimental
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be increased when it is combined with Propylthiouracil.Experimental, Investigational
AminophyllineThe serum concentration of Aminophylline can be increased when it is combined with Propylthiouracil.Approved
ClorindionePropylthiouracil may decrease the anticoagulant activities of Clorindione.Experimental
CymarinThe serum concentration of Cymarin can be increased when it is combined with Propylthiouracil.Experimental
DeslanosideThe serum concentration of Deslanoside can be increased when it is combined with Propylthiouracil.Approved
DicoumarolPropylthiouracil may decrease the anticoagulant activities of Dicoumarol.Approved
DigitoxinThe serum concentration of Digitoxin can be increased when it is combined with Propylthiouracil.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Propylthiouracil.Approved
Digoxin Immune Fab (Ovine)The serum concentration of Digoxin Immune Fab (Ovine) can be increased when it is combined with Propylthiouracil.Approved
DiphenadionePropylthiouracil may decrease the anticoagulant activities of Diphenadione.Experimental
DyphyllineThe serum concentration of Dyphylline can be increased when it is combined with Propylthiouracil.Approved
Ethyl biscoumacetatePropylthiouracil may decrease the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindionePropylthiouracil may decrease the anticoagulant activities of Fluindione.Investigational
GitoformateThe serum concentration of Gitoformate can be increased when it is combined with Propylthiouracil.Experimental
Iodide I-131The therapeutic efficacy of Iodide I-131 can be decreased when used in combination with Propylthiouracil.Approved
Lanatoside CThe serum concentration of Lanatoside C can be increased when it is combined with Propylthiouracil.Experimental
MetildigoxinThe serum concentration of Metildigoxin can be increased when it is combined with Propylthiouracil.Experimental
OleandrinThe serum concentration of Oleandrin can be increased when it is combined with Propylthiouracil.Experimental, Investigational
OuabainThe serum concentration of Ouabain can be increased when it is combined with Propylthiouracil.Approved
PeruvosideThe serum concentration of Peruvoside can be increased when it is combined with Propylthiouracil.Experimental
PhenindionePropylthiouracil may decrease the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonPropylthiouracil may decrease the anticoagulant activities of Phenprocoumon.Approved, Investigational
ProscillaridinThe serum concentration of Proscillaridin can be increased when it is combined with Propylthiouracil.Experimental
TheophyllineThe serum concentration of Theophylline can be increased when it is combined with Propylthiouracil.Approved
TioclomarolPropylthiouracil may decrease the anticoagulant activities of Tioclomarol.Experimental
WarfarinPropylthiouracil may decrease the anticoagulant activities of Warfarin.Approved
Food Interactions
  • Take at the same time everyday.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14690
KEGG Drug
D00562
KEGG Compound
C07569
PubChem Compound
657298
PubChem Substance
46505181
ChemSpider
571424
BindingDB
50133597
ChEBI
8502
ChEMBL
CHEMBL1518
Therapeutic Targets Database
DAP001247
PharmGKB
PA451156
HET
3CJ
Drugs.com
Drugs.com Drug Page
Wikipedia
Propylthiouracil
ATC Codes
H03BA02 — Propylthiouracil
AHFS Codes
  • 68:36.08 — Antithyroid Agents
PDB Entries
4qyq / 5hpw
MSDS
Download (53.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentGraves Diseases1
3CompletedTreatmentPaediatric Thyrotoxicosis1
3RecruitingTreatmentGraves Diseases / Graves Ophthalmopathy / Graves' Ophthalmopathy Worsened1
4Unknown StatusTreatmentEndocrine ophthalmopathy1
Not AvailableCompletedTreatmentPregnancy / Thyroid Diseases1

Pharmacoeconomics

Manufacturers
  • Abbott laboratories pharmaceutical products div
  • Actavis elizabeth llc
  • Anabolic inc
  • Dava pharmaceuticals inc
  • Halsey drug co inc
  • Impax laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lannett co inc
  • Eli lilly and co
  • Mutual pharmaceutical co inc
  • L perrigo co
  • Tablicaps inc
  • Watson laboratories inc
  • West ward pharmaceutical corp
Packagers
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral50 mg
TabletOral50 mg/1
Prices
Unit descriptionCostUnit
Propyl-Thyracil 100 mg Tablet0.34USD tablet
Propyl-Thyracil 50 mg Tablet0.22USD tablet
Propylthiouracil 50 mg tablet0.18USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)219 °CPhysProp
water solubility1200 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP0.4Not Available
logS-2.15ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.466 mg/mLALOGPS
logP1.53ALOGPS
logP1.2ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)8.09ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area41.13 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity48.9 m3·mol-1ChemAxon
Polarizability17.79 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier+0.9045
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.5812
P-glycoprotein inhibitor INon-inhibitor0.8141
P-glycoprotein inhibitor IINon-inhibitor0.9753
Renal organic cation transporterNon-inhibitor0.8407
CYP450 2C9 substrateNon-substrate0.6573
CYP450 2D6 substrateNon-substrate0.7926
CYP450 3A4 substrateNon-substrate0.6664
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9259
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5
Ames testNon AMES toxic0.81
CarcinogenicityNon-carcinogens0.9396
BiodegradationNot ready biodegradable0.9643
Rat acute toxicity2.1786 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9769
hERG inhibition (predictor II)Non-inhibitor0.8423
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.33 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-00dl-9800000000-dd34c50b7aa55979d5f2
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
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-014i-0900000000-f857bb6ee86a6e7b0ab3
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-066r-7900000000-e5e5c265147935fdd8d2
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-9000000000-927304e1ff32407a8d18
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-9000000000-343c26fd83ebb89d346d
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-9000000000-0d1467a930d2ddf9349b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0900000000-0b376a1be2d2d48ad875
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0fk9-0900000000-f095bd0fa6c365161ec9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0900000000-2ce23fa0cb6ec6129e29
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-0900000000-9ee3b1971c716e9a4dc1
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-0900000000-7d9cf3791e4e7800916d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0ik9-5900000000-41be31a4c739b4ea29a4
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03xr-9200000000-8eb9b68ae97914399fc0
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-1900000000-b867c06c7c74b627274c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-0900000000-6549521c2c4645bc9542
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyrimidones. These are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Pyrimidones
Alternative Parents
Pyrimidinethiones / 2-Thiopyrimidines / Hydropyrimidines / Vinylogous amides / Heteroaromatic compounds / Thioureas / Lactams / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds
show 3 more
Substituents
2-thiopyrimidine / Pyrimidinethione / Thiopyrimidine / Pyrimidone / Hydropyrimidine / Heteroaromatic compound / Vinylogous amide / Lactam / Thiourea / Azacycle
show 9 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrimidinethione (CHEBI:8502) / a small molecule (CPD-11429)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Peroxidase activity
Specific Function
Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).
Gene Name
TPO
Uniprot ID
P07202
Uniprot Name
Thyroid peroxidase
Molecular Weight
102961.63 Da
References
  1. Sugawara M, Sugawara Y, Wen K: Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles. Thyroid. 1999 May;9(5):513-8. [PubMed:10365684]
  2. Manzon RG, Holmes JA, Youson JH: Variable effects of goitrogens in inducing precocious metamorphosis in sea lampreys (Petromyzon marinus). J Exp Zool. 2001 Apr 15;289(5):290-303. [PubMed:11241400]
  3. Ferreira AC, de Carvalho Cardoso L, Rosenthal D, de Carvalho DP: Thyroid Ca2+/NADPH-dependent H2O2 generation is partially inhibited by propylthiouracil and methimazole. Eur J Biochem. 2003 Jun;270(11):2363-8. [PubMed:12755690]
  4. Schmutzler C, Bacinski A, Gotthardt I, Huhne K, Ambrugger P, Klammer H, Schlecht C, Hoang-Vu C, Gruters A, Wuttke W, Jarry H, Kohrle J: The ultraviolet filter benzophenone 2 interferes with the thyroid hormone axis in rats and is a potent in vitro inhibitor of human recombinant thyroid peroxidase. Endocrinology. 2007 Jun;148(6):2835-44. Epub 2007 Mar 22. [PubMed:17379648]
  5. Taurog A, Dorris ML: A reexamination of the proposed inactivation of thyroid peroxidase in the rat thyroid by propylthiouracil. Endocrinology. 1989 Jun;124(6):3038-42. [PubMed:2656250]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Peroxidase activity
Specific Function
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production o...
Gene Name
MPO
Uniprot ID
P05164
Uniprot Name
Myeloperoxidase
Molecular Weight
83867.71 Da
References
  1. Lee E, Miki Y, Katsura H, Kariya K: Mechanism of inactivation of myeloperoxidase by propylthiouracil. Biochem Pharmacol. 1990 May 1;39(9):1467-71. [PubMed:2159305]
  2. Kariya K, Lee E, Hirouchi M: Relationship between leukopenia and bone marrow myeloperoxidase in the rat treated with propylthiouracil. Jpn J Pharmacol. 1984 Oct;36(2):217-22. [PubMed:6096612]
  3. Zhang AH, Chen M, Gao Y, Zhao MH, Wang HY: Inhibition of oxidation activity of myeloperoxidase (MPO) by propylthiouracil (PTU) and anti-MPO antibodies from patients with PTU-induced vasculitis. Clin Immunol. 2007 Feb;122(2):187-93. Epub 2006 Oct 27. [PubMed:17070108]
  4. Lee E, Hirouchi M, Hosokawa M, Sayo H, Kohno M, Kariya K: Inactivation of peroxidases of rat bone marrow by repeated administration of propylthiouracil is accompanied by a change in the heme structure. Biochem Pharmacol. 1988 Jun 1;37(11):2151-3. [PubMed:2837228]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
L-ascorbic acid binding
Specific Function
Conversion of dopamine to noradrenaline.
Gene Name
DBH
Uniprot ID
P09172
Uniprot Name
Dopamine beta-hydroxylase
Molecular Weight
69064.45 Da
References
  1. Hidaka H, Nagasaka A: Inhibition of dopamine beta-hydroxylase by anti-thyroid agents, methimazole and propylthiouracil. Biochem Pharmacol. 1977 Jun 1;26(11):1092-3. [PubMed:880264]

Drug created on June 13, 2005 07:24 / Updated on January 14, 2018 10:04