Oxamniquine

Identification

Name
Oxamniquine
Accession Number
DB01096  (APRD01150)
Type
Small Molecule
Groups
Approved
Description

An anthelmintic with schistosomicidal activity against Schistosoma mansoni, but not against other Schistosoma spp. Oxamniquine causes worms to shift from the mesenteric veins to the liver where the male worms are retained; the female worms return to the mesentery, but can no longer release eggs. (From Martidale, The Extra Pharmacopoeia, 31st ed, p121)

Structure
Thumb
Synonyms
  • Mansil
External IDs
Not Available
Product Ingredients
Not Available
Approved Prescription Products
Not Available
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Mansil / Vansil
Brand mixtures
Not Available
Categories
UNII
0O977R722D
CAS number
21738-42-1
Weight
Average: 279.3348
Monoisotopic: 279.158291553
Chemical Formula
C14H21N3O3
InChI Key
XCGYUJZMCCFSRP-UHFFFAOYSA-N
InChI
InChI=1S/C14H21N3O3/c1-9(2)15-7-12-4-3-10-5-11(8-18)14(17(19)20)6-13(10)16-12/h5-6,9,12,15-16,18H,3-4,7-8H2,1-2H3
IUPAC Name
(7-nitro-2-{[(propan-2-yl)amino]methyl}-1,2,3,4-tetrahydroquinolin-6-yl)methanol
SMILES
CC(C)NCC1CCC2=CC(CO)=C(C=C2N1)[N+]([O-])=O

Pharmacology

Indication

For treatment of Schistosomiasis caused by Schistosoma mansoni

Structured Indications
Not Available
Pharmacodynamics

Oxamniquine is an anthelmintic with schistosomicidal activity against Schistosoma mansoni, but not against other Schistosoma spp. Oxamniquine causes worms to shift from the mesenteric veins to the liver where the male worms are retained; the female worms return to the mesentery, but can no longer release egg.

Mechanism of action

Oxamniquine may associate with an irreversible inhibition of the nucleic acid metabolism of the parasites. A hypothesis has been put forth that the drug is activated by a single step, in which a schistosome sulfotransferase enzyme converts oxamniquine into an ester (probably acetate, phosphate, or sulfate). Subsequently, the ester spontaneously dissociates, the resulting electrophilic reactant is capable of alkylation of schistosome DNA.

TargetActionsOrganism
ADNA
other/unknown
Human
Absorption

Well absorbed orally

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Probably hepatic

Route of elimination
Not Available
Half life

1-2.5 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Schistosoma mansoni
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AmodiaquineThe serum concentration of Oxamniquine can be decreased when it is combined with Amodiaquine.Approved
ChloroquineThe serum concentration of Oxamniquine can be decreased when it is combined with Chloroquine.Approved, Vet Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Oxamniquine.Approved
HydroxychloroquineThe serum concentration of Oxamniquine can be decreased when it is combined with Hydroxychloroquine.Approved
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Oxamniquine.Approved, Investigational
PrimaquineThe serum concentration of Oxamniquine can be decreased when it is combined with Primaquine.Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Oxamniquine.Withdrawn
Food Interactions
Not Available

References

Synthesis Reference
US3821228
General References
  1. Filho RP, de Souza Menezes CM, Pinto PL, Paula GA, Brandt CA, da Silveira MA: Design, synthesis, and in vivo evaluation of oxamniquine methacrylate and acrylamide prodrugs. Bioorg Med Chem. 2007 Feb 1;15(3):1229-36. Epub 2006 Nov 16. [PubMed:17134907 ]
External Links
Human Metabolome Database
HMDB15228
KEGG Drug
D00460
KEGG Compound
C07341
PubChem Compound
4612
PubChem Substance
46508789
ChemSpider
4451
ChEBI
78416
ChEMBL
CHEMBL847
Therapeutic Targets Database
DAP000992
PharmGKB
PA164748782
Drugs.com
Drugs.com Drug Page
Wikipedia
Oxamniquine
ATC Codes
P02BA02 — Oxamniquine
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Download (50 KB)

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)147-149 °CPhysProp
water solubility820 mg/LNot Available
logP2.24SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.124 mg/mLALOGPS
logP1.54ALOGPS
logP1.57ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)14.55ChemAxon
pKa (Strongest Basic)9.9ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area90.11 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity79.86 m3·mol-1ChemAxon
Polarizability30.19 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier-0.6502
Caco-2 permeable-0.5759
P-glycoprotein substrateSubstrate0.872
P-glycoprotein inhibitor INon-inhibitor0.6528
P-glycoprotein inhibitor IINon-inhibitor0.8828
Renal organic cation transporterNon-inhibitor0.7578
CYP450 2C9 substrateNon-substrate0.797
CYP450 2D6 substrateNon-substrate0.8735
CYP450 3A4 substrateNon-substrate0.583
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.6334
CYP450 3A4 inhibitorNon-inhibitor0.8603
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8783
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.7461
BiodegradationNot ready biodegradable0.9958
Rat acute toxicity3.5281 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5899
hERG inhibition (predictor II)Inhibitor0.6207
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
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0090000000-cbc05dcd3c76cb5e6dbc
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0090000000-13f1262c88faee196444
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0950000000-082ec38664b574d25a9c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00dj-0900000000-781fed8c05ecf56fc5b6
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-006t-0900000000-9e5d872a8378b48f787f
LC-MS/MS Spectrum - , positiveLC-MS/MSsplash10-00dj-2910000000-90237e532f4d41c89192
Predicted LC-MS/MS Spectrum - 10V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 10V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, NegativePredicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of chemical entities known as nitroquinolines and derivatives. These are compounds containing a nitro group attached to a quinoline moiety.
Kingdom
Chemical entities
Super Class
Organic compounds
Class
Organoheterocyclic compounds
Sub Class
Quinolines and derivatives
Direct Parent
Nitroquinolines and derivatives
Alternative Parents
Hydroquinolines / Nitroaromatic compounds / Secondary alkylarylamines / Aralkylamines / Benzenoids / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Dialkylamines / Azacyclic compounds / Primary alcohols
show 5 more
Substituents
Nitroquinoline / Tetrahydroquinoline / Nitroaromatic compound / Secondary aliphatic/aromatic amine / Aralkylamine / Benzenoid / C-nitro compound / Organic nitro compound / Secondary aliphatic amine / Organic oxoazanium
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
C-nitro compound, quinolines, secondary amino compound, aromatic primary alcohol (CHEBI:78416 )

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Other/unknown
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. Pica-Mattoccia L, Carlini D, Guidi A, Cimica V, Vigorosi F, Cioli D: The schistosome enzyme that activates oxamniquine has the characteristics of a sulfotransferase. Mem Inst Oswaldo Cruz. 2006 Sep;101 Suppl 1:307-12. [PubMed:17308787 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Drug created on June 13, 2005 07:24 / Updated on September 01, 2017 10:36