Progabide (T3D2908)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2009-07-21 20:27:47 UTC
Update Date2014-12-24 20:25:53 UTC
Accession NumberT3D2908
Identification
Common NameProgabide
ClassSmall Molecule
DescriptionProgabide is an analog and prodrug of gamma-aminobutyric acid. It is commonly used in the treatment of epilepsy. It has agonistic activity for both the GABAA and GABAB receptors. Progabide has been investigated for many diseases besides epilepsy, including Parkinson's disease, schizophrenia, clinical depression and anxiety disorder with varying success.
Compound Type
  • Amide
  • Amine
  • Anticonvulsant
  • Antidepressant
  • Antidepressive Agent
  • Antidyskinetic
  • Antiparkinson Agent
  • Drug
  • Ester
  • GABA Agonist
  • Ketone
  • Metabolite
  • Organic Compound
  • Organochloride
  • Organofluoride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Gabren
Gabrene
Halogabide
Progabida
Progabidum
Chemical FormulaC17H16ClFN2O2
Average Molecular Mass334.773 g/mol
Monoisotopic Mass334.088 g/mol
CAS Registry Number62666-20-0
IUPAC Name4-{[(4-chlorophenyl)[(1E)-3-fluoro-6-oxocyclohexa-2,4-dien-1-ylidene]methyl]amino}butanamide
Traditional Nameprogabide
SMILESOC(=N)CCCN\C(C1=CC=C(Cl)C=C1)=C1/C=C(F)C=CC1=O
InChI IdentifierInChI=1S/C17H16ClFN2O2/c18-12-5-3-11(4-6-12)17(21-9-1-2-16(20)23)14-10-13(19)7-8-15(14)22/h3-8,10,21H,1-2,9H2,(H2,20,23)/b17-14+
InChI KeyInChIKey=DWEQWXSKOHHBNT-SAPNQHFASA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as o-quinomethanes. These are organic compounds containing a benzene ring conjugated to a methylidene group and a ketone at carbon atoms 1 and 2, respectively.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbonyl compounds
Direct ParentO-quinomethanes
Alternative Parents
Substituents
  • O-quinomethane
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • Monocyclic benzene moiety
  • Benzenoid
  • Vinylogous amide
  • Carboximidic acid
  • Carboximidic acid derivative
  • Secondary aliphatic amine
  • Enamine
  • Fluoroalkene
  • Haloalkene
  • Secondary amine
  • Vinyl fluoride
  • Vinyl halide
  • Organopnictogen compound
  • Organic oxide
  • Amine
  • Organohalogen compound
  • Organochloride
  • Organofluoride
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point133-135°C
Boiling PointNot Available
Solubility70.9 mg/L
LogP3.06
Predicted Properties
PropertyValueSource
Water Solubility0.0044 g/LALOGPS
logP2.68ALOGPS
logP1.8ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)15.32ChemAxon
pKa (Strongest Basic)4.01ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area72.19 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity91.22 m³·mol⁻¹ChemAxon
Polarizability33.21 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000x-5091000000-45493775f8e316fed3452017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00kr-1029000000-fc0da8ed87727a709a1f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-5059000000-63dcad42741a847ae8ff2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000f-9520000000-da113f6ba6c4a6d23a822016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0129000000-3de1ea119383317ba3552016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000y-6289000000-b086ccb10b99604720a82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9330000000-2be76f698dbbc120b6b12016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-513fcdf8c10f3b29cd132021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0f80-0094000000-8c5c8a6b47f57d482e912021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01q9-0090000000-990d46a622dd2ff2264d2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0029000000-8d3aa9ae2fda5750dbf22021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000t-2196000000-d2a509d2c58ae1850d292021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01qj-3490000000-5a245325ccd99decd7c92021-10-11View Spectrum
Toxicity Profile
Route of ExposureWell absorbed with a bioavailability of 60%
Mechanism of ToxicityProgabide binds to both GABAA and GABAB receptors located on the terminals of primary afferent fibers. Binding to GABAA results in an increased affinity of the GABA receptor for the amino acid, an augmented flux of chloride ions across the terminal membrane, and an increase in the amount of presynaptic inhibition. Activation of the GABAB receptors retards the influx of calcium ions into the terminals, thereby reducing the evoked release of excitatory amino acids and possibly other transmitters.
MetabolismHepatic Half Life: 4 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIndicated for the treatment of epilepsy.
Minimum Risk LevelNot Available
Health EffectsMay cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00837
HMDB IDHMDB14975
PubChem Compound ID5361323
ChEMBL IDCHEMBL287631
ChemSpider ID4514729
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDProgabide
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkProgabide
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Bartholini G, Scatton B, Zivkovic B, Lloyd KG: GABA receptor agonists and extrapyramidal motor function: therapeutic implications for Parkinson's disease. Adv Neurol. 1987;45:79-83. [3030072 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Gamma-aminobutyric acid receptor subunit alpha-1
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 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. [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. [17016423 ]
Target Details
2. Gamma-aminobutyric acid type B receptor subunit 1
General Function:
G-protein coupled gaba receptor activity
Specific Function:
Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen.Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.
Gene Name:
GABBR1
Uniprot ID:
Q9UBS5
Molecular Weight:
108319.4 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]