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Record Information
Version2.0
Creation Date2014-08-30 21:03:31 UTC
Update Date2014-12-24 20:26:52 UTC
Accession NumberT3D4552
Identification
Common NameEszopiclone
ClassSmall Molecule
DescriptionEszopiclone, marketed by Sepracor under the brand-name Lunesta, is a nonbenzodiazepine hypnotic agent (viz., a sedative) used as a treatment for insomnia. Eszopiclone is the active stereoisomer of zopiclone, and belongs to the class of drugs known as cyclopyrrones. Its main selling point is that it is approved by the U.S. Food and Drug Administration for long-term use, unlike almost all other hypnotic sedatives, which are approved only for the relief of short-term (6-8 weeks) insomnia.
Compound Type
  • Amide
  • Amine
  • Drug
  • Ether
  • Food Toxin
  • Hypnotic and Sedative
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-(5S)-6-(5-Chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazin-5-yl 4-methylpiperazine-1-carboxylate
(+)-(5S)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl-4-methylpiperazine-1-carboxylate
(+)-Zopiclone
(S)-6-(5-Chloro-2-pyridinyl)- 7-oxo- 6,7-dihydro- 5H-pyrrolo[3,4-b]pyrazin-5-yl- 4-methyl- 1-piperazinecarboxylate
(S)-Zopiclone
1-Piperazinecarobxylic acid,4-methyl-,(5S)-6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl ester
Dorplen
Esleep
Esopiclone
Estorra
Eszop
Fulnite
Inductal
Isoklon
Lunesta
Nirvan
Noptic
Plessir
Sanilent
Sleepil
Sominex
Sono
Valnoc
Wen Fei
Zopilone
Zopinon
Chemical FormulaC17H17ClN6O3
Average Molecular Mass388.808 g/mol
Monoisotopic Mass388.105 g/mol
CAS Registry Number138729-47-2
IUPAC Name(5S)-6-(5-chloropyridin-2-yl)-7-oxo-5H,6H,7H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
Traditional Namelunesta
SMILES[H][C@@]1(OC(=O)N2CCN(C)CC2)N(C(=O)C2=C1N=CC=N2)C1=NC=C(Cl)C=C1
InChI IdentifierInChI=1S/C17H17ClN6O3/c1-22-6-8-23(9-7-22)17(26)27-16-14-13(19-4-5-20-14)15(25)24(16)12-3-2-11(18)10-21-12/h2-5,10,16H,6-9H2,1H3/t16-/m0/s1
InChI KeyInChIKey=GBBSUAFBMRNDJC-INIZCTEOSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as cyclopyrrolones. Cyclopyrrolones are compounds belonging to a family of pyridin-2-ylpyrrole based chemicals. The pyrrole is usually fused to a benzene, pyrimidine, or dithiin.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrrolopyrazines
Sub ClassCyclopyrrolones
Direct ParentCyclopyrrolones
Alternative Parents
Substituents
  • Cyclopyrrolone
  • Piperazine-1-carboxylic acid
  • 2-heteroaryl carboxamide
  • N-methylpiperazine
  • N-alkylpiperazine
  • Aryl chloride
  • Aryl halide
  • Imidolactam
  • Pyridine
  • Pyrazine
  • Piperazine
  • 1,4-diazinane
  • Heteroaromatic compound
  • Carbamic acid ester
  • Tertiary carboxylic acid amide
  • Amino acid or derivatives
  • Carboxamide group
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactam
  • Carbonic acid derivative
  • Azacycle
  • Carboxylic acid derivative
  • Organonitrogen compound
  • Organooxygen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organic oxide
  • Amine
  • Carbonyl group
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organohalogen compound
  • Organochloride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubilityvery slightly soluble
LogP0.8
Predicted Properties
PropertyValueSource
Water Solubility0.88 g/LALOGPS
logP0.97ALOGPS
logP0.81ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)13.04ChemAxon
pKa (Strongest Basic)6.89ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area91.76 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity95.89 m³·mol⁻¹ChemAxon
Polarizability37.67 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05bb-9212000000-b3e4c2874ff86d2544e1JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0190000000-979bdecccd14f99834e7JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-58198ad5b8e6fb5075fcJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-5917000000-fed7a3a68ceccd2f26beJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ac0-9000000000-ef1623aed48bd5073d7bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0309000000-e2a958d8569e44198c06JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-1901000000-d74484c0d625330ab7cdJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-056r-9510000000-15dec99e5a9537957558JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-8fbf9af9d2708ba6bc8cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000j-0049000000-0d0bcaed2a13fc359e64JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03e9-2695000000-54c5cabfed200237305eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0019000000-8858df62be2425d6d12cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000b-0296000000-2ee50c7aa4e487c88128JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-5591000000-d23576e5504d2099b104JSpectraViewer
Toxicity Profile
Route of ExposureRapidly absorbed following oral administration
Mechanism of ToxicityThe mechanism of action of Eszopiclone is not completely understood. It is thought that Eszopiclone acts on the benzodiazepine receptors as an agonist and interacts with GABA-receptor complexes.
MetabolismFollowing oral administration, eszopiclone is extensively metabolized by oxidation and demethylation. Route of Elimination: Up to 75% of an oral dose of racemic zopiclone is excreted in the urine, primarily as metabolites. Half Life: 6 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of insomnia
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSide effects include viral infection, dry mouth, dizziness, hallucinations, infection, rash, and unpleasant taste, with this relationship clearest for unpleasant taste depending on doses.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00402
HMDB IDNot Available
PubChem Compound ID969472
ChEMBL IDCHEMBL1522
ChemSpider ID839530
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID53760
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEszopiclone
References
Synthesis Reference

Marioara MENDELOVICI, Anita LIBERMAN, Alex MAINFELD, Nina FINKELSTEIN, “METHODS FOR PREPARING ESZOPICLONE CRYSTALLINE FORM A, SUBSTANTIALLY PURE ESZOPICLONE AND OPTICALLY ENRICHED ESZOPICLONE.” U.S. Patent US20070270590, issued November 22, 2007.

MSDST3D4552.pdf
General ReferencesNot Available
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Cholesterol binding
Specific Function:
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
Gene Name:
TSPO
Uniprot ID:
P30536
Molecular Weight:
18827.81 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 ]
  3. Becker PM, Sattar M: Treatment of sleep dysfunction and psychiatric disorders. Curr Treat Options Neurol. 2009 Sep;11(5):349-57. [19744401 ]
  4. Jufe GS: [New hypnotics: perspectives from sleep physiology]. Vertex. 2007 Jul-Aug;18(74):294-9. [18265473 ]
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. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [19942638 ]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [18973287 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA2
Uniprot ID:
P47869
Molecular Weight:
51325.85 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [19942638 ]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [18973287 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA3
Uniprot ID:
P34903
Molecular Weight:
55164.055 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [19942638 ]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [18973287 ]
General Function:
Transporter activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA5
Uniprot ID:
P31644
Molecular Weight:
52145.645 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [19942638 ]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [18973287 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA6
Uniprot ID:
Q16445
Molecular Weight:
51023.69 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>15 uMNot AvailableBindingDB 26265
References
  1. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [18973287 ]
General Function:
Sphingosine-1-phosphate receptor activity
Specific Function:
Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis.
Gene Name:
S1PR3
Uniprot ID:
Q99500
Molecular Weight:
42249.805 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>49.8 uMNot AvailableBindingDB 26265
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
8. GABA-A receptor (anion channel) (Protein Group)
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).
Included Proteins:
P14867 , P47869 , P34903 , P48169 , P31644 , Q16445 , P18505 , P47870 , P28472 , O14764 , P78334 , Q8N1C3 , P18507 , Q99928 , O00591 , Q9UN88