6-(5-chloropyridin-2-yl)-7-oxo-5H,6H,7H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate

• ChemBase ID: 1068
• Molecular Formular: C17H17ClN6O3
• Molecular Mass: 388.80828
• Monoisotopic Mass: 388.10506611
• SMILES: Clc1ccc(N2C(OC(=O)N3CCN(CC3)C)c3nccnc3C2=O)nc1
• Canonical SMILES: CN1CCN(CC1)C(=O)OC1c2nccnc2C(=O)N1c1ccc(cn1)Cl
• InChI: InChI=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
• InChIKey: GBBSUAFBMRNDJC-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 6-(5-chloropyridin-2-yl)-7-oxo-5H,6H,7H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
• IUPAC Traditional name: zopiclone; 6-(5-chloropyridin-2-yl)-7-oxo-5H,6H,7H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
• Brand Name: Amoban; Amovane; Imovance; Imovane; Sopivan; Zimovane; Nu-Zopiclone; Novo-zopiclone; Ran-zopiclone; Rhovane; Ximovan; Imovane, Zimovane
• Synonyms: 6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate; 4-Methyl-1-piperazinecarboxylic acid 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl ester; Zopiclone; Zopiclona [INN-Spanish]; Zopiclone [Ban:Inn:Jan]; Zopiclonum [INN-Latin]; (+-)-zopiclone; Zopiclone; Imovance; 4-Methyl-1-piperazine-carboxylic Acid 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl Ester; RP-27267; Amoban; Limovan; Sopivan; Ximovan; Imovane; Zimovane; Lunesta

Database IDs

• CAS Number: 43200-80-2
• EC Number: 256-138-9
• MDL Number: MFCD00133931
• PubChem SID: 160964531; 46505233; 24278148
• PubChem CID: 5735
• CHEBI ID: 32315
• ATC CODE: N05CF01
• CHEMBL: 135400
• Chemspider ID: 5533
• DrugBank ID: DB01198
• KEGG ID: D01372
• Unique Ingredient Identifier: 03A5ORL08Q
• Wikipedia Title: Zopiclone

CALCULATED PROPERTIES

JChem

• Acid pKa: 13.038308
• H Acceptors: 6
• H Donor: 0
• LogD (pH = 5.5): -0.59504867
• LogD (pH = 7.4): 0.6902288
• Log P: 0.80654305
• Molar Refractivity: 95.8855 cm^3
• Polarizability: 37.123627 Å^3
• Polar Surface Area: 91.76 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.97
• LOG S: -2.64
• Solubility (Water): 8.85e-01 g/l

PROPERTIES

Physical Property

• Solubility: 0.151 mg/mL at 25 oC [MEYLAN,WM et al. (1996)]; Acetone; Chloroform; DMSO; DMSO: soluble2 mg/mL; H2O: insoluble
• Apperance: Off-White Solid
• Melting Point: 173-175°C (dec.)
• Hydrophobicity(logP): 0.8

Safety Information

• Storage Condition: -20°C; Refrigerator
• RTECS: TL1425000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 20/21/22-36/37/38-62
• Safety Statements: 26-36
• GHS Pictograms: GHS07; GHS08
• GHS Signal Word: Warning
• GHS Hazard statements: H302-H312-H315-H319-H332-H335-H361
• GHS Precautionary statements: P261-P280-P305 + P351 + P338
• Personal Protective Equipment: Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• Drug Control: USDEA Schedule IV; psychotrope; regulated under CDSA - not available from Sigma-Aldrich Canada

Pharmacology Properties

• Admin Routes: Oral tablets, 3.75mg (UK), 5 or 7.5 mg
• Bioavailability: 52-59% bound to plasma protein
• Excretion: Urine
• Half Life: ~6 hours ; ~9 hours for over 65
• Metabolism: Various cytochrome P450 liver enzymes
• Legal Status: POM (UK); Schedule IV (US)
• Pregnancy Category: C (US)
• Gene Information: human ... BZRAP1(9256)
• Mechanism of Action: The mechanism of action of zopiclone is similar to benzodiazepines, with similar effects on locomotor activity and on dopamine and serotonin turnover

Product Information

• Salt Data: Free Base
• Application(s): Anticonvulsant; Psychosedative; Sedative; Tranquilizer

DETAILS

DrugBank - DB01198

• Drug Groups: approved
• Description: Zopiclone is a novel hypnotic agent used in the treatment of insomnia. Its mechanism of action is based on modulating benzodiazepine receptors. In addition to zopiclone's benzodiazepine pharmacological properties it also has some barbiturate like properties.
• Indication: For the short-term treatment of insomnia.
• Pharmacology: Zopiclone is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABA_BZ) receptor complex. Subunit modulation of the GABA_BZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor.
• Toxicity: Rare individual instances of fatal outcomes following overdose with racemic zopiclone have been reported in European postmarketing reports, most often associated with overdose with other CNS-depressant agent. Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing.
• Affected Organisms: Humans and other mammals
• Biotransformation: Extensively metabolized in the liver via decarboxylation (major pathway), demethylation, and side chain oxidation. Metabolites include an N-oxide derivative (weakly active; approximately 12% of a dose) and an N-desmethyl metabolite (inactive; approximately 16%). Approximately 50% of a dose is converted to other inactive metabolites via decarboxylation. Hepatic microsomal enzymes are apparently not involved in zopiclone clearance.
• Absorption: Rapidly absorbed following oral administration.
• Half Life: Elimination half life is approximately 5 hours (range 3.8 to 6.5 hours) and is prolonged to 11.9 hours in patients with hepatic insufficiency.
• Protein Binding: Approximately 45%
• References: Liu HJ, Sato K, Shih HC, Shibuya T, Kawamoto H, Kitagawa H: Pharmacologic studies of the central action of zopiclone: effects on locomotor activity and brain monoamines in rats. Int J Clin Pharmacol Ther Toxicol. 1985 Mar;23(3):121-8. [Pubmed] ; Sato K, Hong YL, Yang MS, Shibuya T, Kawamoto H, Kitagawa H: Pharmacologic studies of central actions of zopiclone: influence on brain monoamines in rats under stressful condition. Int J Clin Pharmacol Ther Toxicol. 1985 Apr;23(4):204-10. [Pubmed] ; Dundar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T: Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Hum Psychopharmacol. 2004 Jul;19(5):305-22. [Pubmed] ; Blanchard JC, Julou L: Suriclone: a new cyclopyrrolone derivative recognizing receptors labeled by benzodiazepines in rat hippocampus and cerebellum. J Neurochem. 1983 Mar;40(3):601-7. [Pubmed] ; Julou L, Bardone MC, Blanchard JC, Garret C, Stutzmann JM: Pharmacological studies on zopiclone. Pharmacology. 1983;27 Suppl 2:46-58. [Pubmed]
• External Links: Wikipedia; Drugs.com

Selleck Chemicals - S1446

Related research area: Neurological Disease

Sigma Aldrich - Z4900

Biochem/physiol Actions
Benzodiazepine receptor agonist
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. Z4900.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - Z700500

Cyclopyrrolone member of a family of non-benzodiazepine GABAA receptor agonists. This is a controlled substance (depressant) in the US but not in Canada. Sedative, hypnotic.

REFERENCES

• Liu HJ, Sato K, Shih HC, Shibuya T, Kawamoto H, Kitagawa H: Pharmacologic studies of the central action of zopiclone: effects on locomotor activity and brain monoamines in rats. Int J Clin Pharmacol Ther Toxicol. 1985 Mar;23(3):121-8. Pubmed
• Sato K, Hong YL, Yang MS, Shibuya T, Kawamoto H, Kitagawa H: Pharmacologic studies of central actions of zopiclone: influence on brain monoamines in rats under stressful condition. Int J Clin Pharmacol Ther Toxicol. 1985 Apr;23(4):204-10. Pubmed
• Dundar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T: Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Hum Psychopharmacol. 2004 Jul;19(5):305-22. Pubmed
• Blanchard JC, Julou L: Suriclone: a new cyclopyrrolone derivative recognizing receptors labeled by benzodiazepines in rat hippocampus and cerebellum. J Neurochem. 1983 Mar;40(3):601-7. Pubmed
• Julou L, Bardone MC, Blanchard JC, Garret C, Stutzmann JM: Pharmacological studies on zopiclone. Pharmacology. 1983;27 Suppl 2:46-58. Pubmed
• http://en.wikipedia.org/wiki/Zopiclone
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