Identification

Name
Gaboxadol
Accession Number
DB06554
Type
Small Molecule
Groups
Investigational
Description

Gaboxadol also known as 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) is an experimental sleep aid drug developed by Lundbeck and Merck. In March, 2007, Merck and H. Lundbeck cancelled work on the drug, citing safety concerns and the failure of an efficacy trial. It acts on the GABA system, but possibly in a different way from benzodiazepines, nonbenzodiazepines and barbiturates - (Valium, Sodium Pentothal, Ambien etc.). Lundbeck states that gaboxadol also increases deep sleep (stage 4). It is, however, not reinforcing like benzodiazepines are. [Wikipedia]

Structure
Thumb
Synonyms
  • 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol
  • THIP
External IDs
LU-02-030 / MK-0928
Categories
UNII
K1M5RVL18S
CAS number
64603-91-4
Weight
Average: 140.1399
Monoisotopic: 140.05857751
Chemical Formula
C6H8N2O2
InChI Key
ZXRVKCBLGJOCEE-UHFFFAOYSA-N
InChI
InChI=1S/C6H8N2O2/c9-6-4-1-2-7-3-5(4)10-8-6/h7H,1-3H2,(H,8,9)
IUPAC Name
2H,3H,4H,5H,6H,7H-[1,2]oxazolo[5,4-c]pyridin-3-one
SMILES
O=C1NOC2=C1CCNC2

Pharmacology

Indication

Investigated for use/treatment in sleep disorders and insomnia.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
Not Available
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
DrugInteractionDrug group
DoxofyllineThe serum concentration of Doxofylline can be decreased when it is combined with Gaboxadol.Approved, Investigational
MefloquineThe therapeutic efficacy of Gaboxadol can be decreased when used in combination with Mefloquine.Approved
MianserinThe therapeutic efficacy of Gaboxadol can be decreased when used in combination with Mianserin.Approved, Investigational
OrlistatThe serum concentration of Gaboxadol can be decreased when it is combined with Orlistat.Approved, Investigational
PregabalinThe therapeutic efficacy of Gaboxadol can be decreased when used in combination with Pregabalin.Approved, Illicit, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D04282
KEGG Compound
C13693
PubChem Compound
3448
PubChem Substance
175427072
ChemSpider
3330
BindingDB
82002
ChEBI
34373
ChEMBL
CHEMBL312443
Wikipedia
Gaboxadol

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAngelman's syndrome / Fragile X Syndrome (FXS)1
2CompletedTreatmentMajor Depressive Disorder (MDD)1
2RecruitingTreatmentAngelman's syndrome1
3CompletedTreatmentPrimary Insomnia6
3CompletedTreatmentSleeplessness3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility16.6 mg/mLALOGPS
logP-1.3ALOGPS
logP-2ChemAxon
logS-0.93ALOGPS
pKa (Strongest Acidic)5.12ChemAxon
pKa (Strongest Basic)8.85ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area50.36 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity35.5 m3·mol-1ChemAxon
Polarizability13.31 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Aralkylamines
Alternative Parents
Isoxazoles / Heteroaromatic compounds / Oxacyclic compounds / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Hydrocarbon derivatives
Substituents
Aralkylamine / Heteroaromatic compound / Isoxazole / Azole / Oxacycle / Azacycle / Organoheterocyclic compound / Secondary amine / Secondary aliphatic amine / Organic oxygen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
oxazole (CHEBI:34373)

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
L-proline transmembrane transporter activity
Specific Function
Neutral amino acid/proton symporter. Has a pH-dependent electrogenic transport activity for small amino acids such as glycine, alanine and proline. Besides small apolar L-amino acids, it also recog...
Gene Name
SLC36A1
Uniprot ID
Q7Z2H8
Uniprot Name
Proton-coupled amino acid transporter 1
Molecular Weight
53075.045 Da
References
  1. Larsen M, Holm R, Jensen KG, Sveigaard C, Brodin B, Nielsen CU: 5-Hydroxy-L-tryptophan alters gaboxadol pharmacokinetics in rats: involvement of PAT1 and rOat1 in gaboxadol absorption and elimination. Eur J Pharm Sci. 2010 Jan 31;39(1-3):68-75. doi: 10.1016/j.ejps.2009.10.013. Epub 2009 Nov 10. [PubMed:19900542]

Drug created on March 19, 2008 10:36 / Updated on December 01, 2017 15:39