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Identification
NamePropylthiouracil
Accession NumberDB00550  (APRD00297)
TypeSmall Molecule
GroupsApproved
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 Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PMS-propylthiouraciltablet100 mgoralPharmascience IncNot applicableNot applicableCanada
PMS-propylthiouraciltablet50 mgoralPharmascience IncNot applicableNot applicableCanada
Propyl-thyraciltablet100 mgoralPaladin Labs Inc1945-12-31Not applicableCanada
Propyl-thyraciltablet50 mgoralPaladin Labs Inc1951-12-31Not applicableCanada
Propylthiouraciltablet50 mg/1oralClinical Solutions Wholesale2010-01-29Not applicableUs
Propylthiouraciltablet50 mg/1oralAmerican Health Packaging2015-09-15Not applicableUs
Propylthiouraciltablet50 mg/1oralDAVA Pharmaceuticals, Inc.1947-07-28Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-propylthiouraciltablet100 mgoralApotex IncNot applicableNot applicableCanada
Apo-propylthiouraciltablet50 mgoralApotex IncNot applicableNot applicableCanada
Propylthiouraciltablet50 mg/1oralWest ward Pharmaceutical Corp1971-07-23Not applicableUs
Propylthiouraciltablet50 mg/1oralREMEDYREPACK INC.2012-03-23Not applicableUs
Propylthiouraciltablet50 mg/1oralAv Kare, Inc.1997-01-012016-02-11Us
Propylthiouraciltablet50 mg/1oralRebel Distributors Corp.1971-07-23Not applicableUs
Propylthiouraciltablet50 mg/1oralREMEDYREPACK INC.2013-03-20Not applicableUs
Propylthiouraciltablet50 mg/1oralNcs Health Care Of Ky, Inc Dba Vangard Labs1973-01-09Not applicableUs
Propylthiouraciltablet50 mg/1oralCardinal Health1982-01-01Not applicableUs
Propylthiouraciltablet50 mg/1oralActavis Elizabeth LLC2006-01-15Not applicableUs
Propylthiouraciltablet50 mg/1oralCardinal Health2006-01-15Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AntiroidBu Kwang
PropilPfizer
PropilracilBiolab
PropycilAdmeda
ProracylGenopharm
ProthiucilPhafag
ProthurilUni-Pharma
PTUAlkaloid
ThiuragylTanabe Mitsubishi Pharma
ThyrosanSun-Farm
TiotilNevada Pharma
TirostatMetlen
UracilPharmasant
Brand mixturesNot Available
SaltsNot Available
Categories
UNII721M9407IY
CAS number51-52-5
WeightAverage: 170.232
Monoisotopic: 170.051383642
Chemical FormulaC7H10N2OS
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentPyrimidones
Alternative Parents
Substituents
  • Pyrimidone
  • Pyrimidinethione
  • Hydropyrimidine
  • Heteroaromatic compound
  • Vinylogous amide
  • Thiourea
  • Lactam
  • Azacycle
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed to manage hyperthyroidism which is due to an overactive thyroid gland (Grave's disease).
PharmacodynamicsPropylthiouracil 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 actionPropylthiouracil 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.
Related Articles
AbsorptionWell absorbed following oral administration.
Volume of distributionNot Available
Protein binding82%
MetabolismNot Available
Route of eliminationPropylthiouracil 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 life2 hours
ClearanceNot Available
ToxicityOral, rat: LD50 = 1250 mg/kg.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point219 °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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.33 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-00dl-9800000000-dd34c50b7aa55979d5f2View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesH03BA02
AHFS Codes
  • 68:36.08
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (53.4 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolPropylthiouracil may decrease the anticoagulant activities of Acenocoumarol.
AminophyllineThe serum concentration of Aminophylline can be increased when it is combined with Propylthiouracil.
ClozapineThe risk or severity of adverse effects can be increased when Propylthiouracil is combined with Clozapine.
DicoumarolPropylthiouracil may decrease the anticoagulant activities of Dicoumarol.
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Propylthiouracil.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Propylthiouracil.
Sodium Iodide I-131The therapeutic efficacy of Sodium Iodide I-131 can be decreased when used in combination with Propylthiouracil.
TheophyllineThe serum concentration of Theophylline can be increased when it is combined with Propylthiouracil.
WarfarinPropylthiouracil may decrease the anticoagulant activities of Warfarin.
Food Interactions
  • Take at the same time everyday.

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
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 of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity.
Gene Name:
MPO
Uniprot ID:
P05164
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
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 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23