Identification

Name
Uracil mustard
Accession Number
DB00791  (APRD00130)
Type
Small Molecule
Groups
Approved
Description

Nitrogen mustard derivative of uracil. It is a alkylating antineoplastic agent that is used in lymphatic malignancies, and causes mainly gastrointestinal and bone marrow damage. [PubChem]

Structure
Thumb
Synonyms
  • 5-(Di-2-chloroethyl)aminouracil
  • 5-[Bis(2-chloroethyl)amino]-2,4(1H,3H)-pyrimidinedione
  • 5-[Di(beta-chloroethyl)amino]uracil
  • 5-Aminouracil mustard
  • 5-N,N-Bis(2-chloroethyl)aminouracil
  • Aminouracil mustard
  • Uracil mustard
  • Uracil nitrogen mustard
  • Uramustine
External IDs
NSC-34462 / U-8344
International/Other Brands
Uracil Mustard (Upjohn)
Categories
UNII
W7KQ46GJ8U
CAS number
66-75-1
Weight
Average: 252.098
Monoisotopic: 251.022832025
Chemical Formula
C8H11Cl2N3O2
InChI Key
IDPUKCWIGUEADI-UHFFFAOYSA-N
InChI
InChI=1S/C8H11Cl2N3O2/c9-1-3-13(4-2-10)6-5-11-8(15)12-7(6)14/h5H,1-4H2,(H2,11,12,14,15)
IUPAC Name
5-[bis(2-chloroethyl)amino]-1,2,3,4-tetrahydropyrimidine-2,4-dione
SMILES
ClCCN(CCCl)C1=CNC(=O)NC1=O

Pharmacology

Indication

Used for its antineoplastic properties.

Structured Indications
Not Available
Pharmacodynamics

Uracil Mustard selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of Uracil Mustard-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed.

Mechanism of action

After activation, it binds preferentially to the guanine and cytosine moieties of DNA, leading to cross-linking of DNA, thus inhibiting DNA synthesis and function.

TargetActionsOrganism
UDNA
intercalation
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

5%

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
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Uracil mustard.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Uracil mustard.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Uracil mustard.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Uracil mustard.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Uracil mustard.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Uracil mustard.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Uracil mustard.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Uracil mustard.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Uracil mustard.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Uracil mustard.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Uracil mustard.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Uracil mustard.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Uracil mustard.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Uracil mustard.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Uracil mustard.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Uracil mustard.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Uracil mustard.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Uracil mustard.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Uracil mustard.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14929
KEGG Drug
D06265
KEGG Compound
C11686
PubChem Compound
6194
PubChem Substance
46506168
ChemSpider
5959
ChEBI
9884
ChEMBL
CHEMBL1488
Therapeutic Targets Database
DAP000990
PharmGKB
PA451830
Wikipedia
Uracil_mustard

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Shire development inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)206 dec °CPhysProp
water solubility1070 mg/LNot Available
logP1.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.32 mg/mLALOGPS
logP0.79ALOGPS
logP0.41ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)9.05ChemAxon
pKa (Strongest Basic)1.61ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area61.44 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity58.35 m3·mol-1ChemAxon
Polarizability22.91 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8672
Blood Brain Barrier+0.7711
Caco-2 permeable-0.6657
P-glycoprotein substrateSubstrate0.5716
P-glycoprotein inhibitor INon-inhibitor0.7111
P-glycoprotein inhibitor IINon-inhibitor0.9146
Renal organic cation transporterNon-inhibitor0.63
CYP450 2C9 substrateNon-substrate0.7045
CYP450 2D6 substrateNon-substrate0.7938
CYP450 3A4 substrateNon-substrate0.5662
CYP450 1A2 substrateNon-inhibitor0.8493
CYP450 2C9 inhibitorNon-inhibitor0.6858
CYP450 2D6 inhibitorNon-inhibitor0.894
CYP450 2C19 inhibitorInhibitor0.5511
CYP450 3A4 inhibitorNon-inhibitor0.7064
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6569
Ames testAMES toxic0.718
CarcinogenicityNon-carcinogens0.9019
BiodegradationNot ready biodegradable0.9962
Rat acute toxicity3.4851 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6391
hERG inhibition (predictor II)Non-inhibitor0.5087
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0w29-9730000000-047cc283312feb25a4ed
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 nitrogen mustard compounds. These are compounds having two beta-haloalkyl groups bound to a nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Nitrogen mustard compounds
Direct Parent
Nitrogen mustard compounds
Alternative Parents
Dialkylarylamines / Pyrimidones / Aminopyrimidines and derivatives / Hydropyrimidines / Vinylogous amides / Heteroaromatic compounds / Ureas / Lactams / Azacyclic compounds / Organopnictogen compounds
show 5 more
Substituents
Nitrogen mustard / Tertiary aliphatic/aromatic amine / Dialkylarylamine / Aminopyrimidine / Pyrimidone / Hydropyrimidine / Pyrimidine / Heteroaromatic compound / Vinylogous amide / Lactam
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
nitrogen mustard, aminouracil (CHEBI:9884)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Unknown
Actions
Intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Hartley JA, Forrow SM, Souhami RL: Effect of ionic strength and cationic DNA affinity binders on the DNA sequence selective alkylation of guanine N7-positions by nitrogen mustards. Biochemistry. 1990 Mar 27;29(12):2985-91. [PubMed:2337578]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:42