Зопиклон , Zopiclone, زوبيكلون , 佐匹克隆

ZOPICLONE

зопиклон 

زوبيكلون 

佐匹克隆 

(±)-Zopiclone

1-Piperazinecarboxylic acid, 4-methyl-, 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl ester 

256-138-9 [EINECS]

43200-80-2 [RN]

Structural formula

UV- Spectrum

Conditions : Concentration - 1 mg / 100 ml
The solvent designation schedule	methanol	water	0.1М HCl	0.1M NaOH
maximum absorption	There  decay	303 nm	304 nm	277 nm  237 nm
	-	362	364	199 390
e	-	10500	10500	5800 11300

IR - spectrum

Wavelength (μm)
Wave number (cm -1 )

MASS spectrum

Range
10 largest peaks:
Peak	42	56	99	112	139	143	217	245	246	247
Value	155	231	280	283	209	999	279	719	156	250

References

• UV and IR Spectra. H.-W. Dibbern, R.M. Muller, E. Wirbitzki, 2002 ECV
• NIST/EPA/NIH Mass Spectral Library 2008
• Handbook of Organic Compounds. NIR, IR, Raman, and UV-Vis Spectra Featuring Polymers and Surfactants, Jr., Jerry Workman. Academic Press, 2000.
• Handbook of ultraviolet and visible absorption spectra of organic compounds, K. Hirayama. Plenum Press Data Division, 1967.

Brief background information

Salt	ATC	formula	MM	CASE
-	N05CF01	C 17 H 17 ClN 6 O 3	388.82 g / mol	43200-80-2

Application

• sedative
• hypnotic

Classes substance

• chlorine compounds
  • oxo
    • Esters of 1-piperazinecarboxylate
      • pyridines
        • Pirrolo [3,4-b] piraziny

Synthesis Way

Синтез a)

Trade names

country	Tradename	Manufacturer
Germany	Optydorm	DOLORGIET
	Somnosan	Hormos
	Ksimovan	Sanofi-Aventis
	Zop	HEXAL
	Zopi-cigar	Actavis
	various generic drugs
France	imovane	SanofiAventis
	Noktireks	Sanofi-Synthélabo
United Kingdom	Snowman	SanofiAventis
Italy	imovane	SanofiAventis
	tion	THERE
Japan	Amoʙan	Sanofi-Aventis; Chugai; Mitsubishi
Ukraine	imovane	Sanofi Winthrop Indastria, France
	various generic drugs

Formulations

• coated tablets 7.5 mg;
• Tablets 7.5 mg, 10 mg

References

• DOS 2 300 491 (Rhône-Poulenc; appl. 5.1.1973; F-prior. 7.1.1972, 9.9.1972).
• US 3 862 149 (Rhône-Poulenc; 21.1.1975; F-prior. 7.1.1972, 9.9.1972).

Two major zopiclone metabolites.

CAS Registry No.:	43200-80-2
Molecular Formula:	C17H17ClN6O3	Molecular Weight:	388.8
Compound Name:
zopiclone 1-piperazinecarboxylic acid, 4-methyl-, 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo(3,4-b)pyrazin-5-yl ester 4-methyl-1-piperazinecarboxylic acid 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo(3,4-b)-pyrazin-5-yl ester 4-methyl-1-piperazinecarboxylic acid-6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo(3,4-b)-pyrazin-5-yl ester 6-(5-chloro-2-pyridyl)-6,7-dihydro-7-oxo-5H-pyrrolo(3,4-b)pyrazin-5-yl 4-methyl-1-piperazinecarboxylate 6-(5-chloro-pyridin-2-yl)-5((4-methyl-1-piperazinyl)carbonyloxy)-7-oxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine 6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazin-5-yl 4-methylpiperazine-1-carboxylate amoban (R) imovane

Zopiclone (Imovance), 4-methyl-1-piperzinecarboxylic acid 6-(5-chloro-2- pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl ester (Figure 1) is one of the non benzodiazepine sedative-hypnotics of the cyclopyrrolone class, sold by Rhone-Poulene Company in France since 1987. Although structurally unrelated to benzodiazepines, its pharmacological profile is similar, exhibiting sedative-hypnotic, anxiolytic, myorelaxant, and anticonvulsant activity.[1] Other than the first generation barbiturates and the second-generation benzodiazepines, zopiclone, which is widely used in Europe as well as other regions worldwide,[2,3] as a representative of the third generation sedative-hypnotic drugs, has been shown to be free from residual effects on performance and psychological function the day after intake and from the risks of accumulation because of its short elimination half-life (3.5 to 6.5 hours).[3,4] It is indicated for the short term treatment of insomnia, transient, situational or chronic insomnia, and insomnia secondary to psychiatric disturbances.[3]

REFERENCES 1. Mann, K.; Bauer, H.; Hiemke, C.; Ro¨schke, J.; Wetzel, H.; Benkert, O. Acute, subchronic and discontinuation effects of zopiclone on sleep EEG and nocturnal melatonin secretion. Eur. Neuropsychopharm. 1996, 6 (3), 163– 168. Structure Elucidation of Sedative-Hypnotic Zopiclone 359 Downloaded by [Dalhousie University] at 22:10 19 December 2012

 2. Le´ger, D.; Janus, C.; Pellois, A.; Quera-Salva, M.A.; Dreyfus, J.P. Sleep, morning alertness and quality of life in subjects treated with zopiclone and in good sleepers. study comparing 167 patients and 381 good sleepers. Eur. Psychiat. 1995, 10 (973) Suppl. 3, 99s – 102s.

3. Piperaki, S.; Parissi-Poulou, M. Enantiomeric separation of zopiclone, its metabolites and products of degradation on a b-cyclodextrin bonded phase. J. Chromatogr. A 1996, 729 (1 – 2), 19 – 28

Spectral Data Analyses and Structure Elucidation of Sedative‐Hypnotic Zopiclone

Xin Ming , Hongzhen Lian  & Wei Zhu

Pages 349-360 | Received 10 Sep 2006, Accepted 18 Oct 2006, Published online: 13 Oct 2010

• Download citation
 
• http://dx.doi.org/10.1080/10739140701255656

Zopiclone

Systematic (IUPAC) name
(RS)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
Clinical data
Trade names	Imovane, Zimovane
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: C US: C (Risk not ruled out)
Routes of administration	Oral tablets, 3.75 mg (UK), 5 or 7.5 mg
Legal status
Legal status	AU: S4 (Prescription only) UK: Class C (POM) US: Schedule IV
Pharmacokinetic data
Bioavailability	75-80%[1]
Protein binding	52–59%
Metabolism	Hepatic through CYP3A4and CYP2E1
Biological half-life	~5 hours (3.5–6.5 hours) ~7–9 hours for over 65
Excretion	Urine (80%)
Identifiers
CAS Number	43200-80-2
ATC code	N05CF01 (WHO)
PubChem	CID 5735
IUPHAR/BPS	7430
DrugBank	DB01198
ChemSpider	5533
UNII	03A5ORL08Q
KEGG	D01372
ChEBI	CHEBI:32315
ChEMBL	CHEMBL135400
PDB ligand ID	ZPC (PDBe, RCSB PDB)
Chemical data
Formula	C17H17ClN6O3
Molar mass	388.808 g/mol
3D model (Jmol)	Interactive image

REF http://shodhganga.inflibnet.ac.in/bitstream/10603/46826/9/09_part%20a%20section%202.pdf

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1-(m-tolylethynyl)cyclobutan-1-ol

Silver-initiated radical ring expansion/fluorination of ethynyl cyclobutanols: efficient synthesis of monofluoroethenyl cyclopentanones

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC02656G, Communication

Qingshan Tian, Bin Chen, Guozhu Zhang
A stereoselective synthesis of [small beta]-halogenated 2-methylenecyclopentanones via silver-catalyzed formal ring expansion using water as the cosolvent is described.

Silver-initiated radical ring expansion/fluorination of ethynyl cyclobutanols: efficient synthesis of monofluoroethenyl cyclopentanones

Qingshan Tian,^a   Bin Chen^a and   Guozhu Zhang*^a  

*

Corresponding authors

^a

State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China
E-mail: guozhuzhang@sioc.ac.cn

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC02656G

A stereoselective synthesis of β-halogenated 2-methylenecyclopentanones via silver-catalyzed formal ring expansion using water as the cosolvent is described. A variety of 2-methylenecyclopentanones with fluoro, chloro and bromo functionalities are efficiently prepared from 1-alkynyl cyclobutanols. This method offers facile access to halogenated complex molecules which are not only useful chemicals but also valuable building blocks for further derivatizations.

1-(m-tolylethynyl)cyclobutan-1-ol (1b) Yield: 89%; Yellow oil;

1H NMR (400 MHz, CDCl3)

δ 7.25 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H), 7.10 (d, J = 7.5 Hz, 1H), 2.51 (dt, J = 15.8, 6.3 Hz, 2H), 2.34 (t, J = 9.3 Hz, 2H), 2.30 (s, 3H), 1.85 (m, 2H);

13C NMR (100 MHz, CDCl3)

δ 137.94, 132.27, 129.19, 128.72, 128.17, 122.49, 92.16, 83.58, 68.31, 38.64, 21.20, 12.98; HRMS (EI+ , 70 eV): C13H14O [M]+ : calcd. 186.1045, found 186.1047

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Valdetamide

CAS Registry Number: 512-48-1

CAS Name: 2,2-Diethyl-4-pentenamide

Additional Names: diethylallylacetamide

Trademarks: Novonal (Hoechst)

Molecular Formula: C9H17NO

Molecular Weight: 155.24

Percent Composition: C 69.63%, H 11.04%, N 9.02%, O 10.31%

Literature References: Description: Bockmühl, Schaumann, Dtsch. Med. Wochenschr. 54, 270 (1928). Pharmacokinetics and metabolism: H. Uehleke, M. Brinkschulte-Freitas, Arch. Pharmacol. 302, 11 (1978). TLC determn in urine: E. Klug, P. Toffel, Arzneim.-Forsch. 29, 1651 (1979).

Properties: White powder, mp 75-76°. Sol in 120 parts water; freely sol in alcohol, ether.

Melting point: mp 75-76°

Therap-Cat: Sedative, hypnotic.

Keywords: Sedative/Hypnotic; Amides.

Valdetamid (Valdetamide)

Structural formula

UV - spectrum

Conditions : Concentration - 50 mg / 100 ml
The solvent designation schedule	methanol	Water	0.1 M HCl	0.1M NaOH
maximum absorption	-	-	-	-
	-	-	-	-
ε	-	-	-	-

IR - spectrum

Wavelength (μm)
Wave number (cm -1 )

Range
10 largest peaks:
Peak	53	55	57	67	69	81	112	126	127	140
Value	152	848	115	141	929	156	286	999	338	238

References

• UV and IR Spectra. H.-W. Dibbern, RM Muller, E. Wirbitzki, 2002 ECV
• NIST / EPA / NIH Mass Spectral Library 2008
• Handbook of Organic Compounds. NIR, IR, Raman, and UV-Vis Spectra Featuring Polymers and Surfactants, Jr., Jerry Workman.Academic Press, 2000.
• Handbook of ultraviolet and visible absorption spectra of organic compounds, K. Hirayama. Plenum Press Data Division, 1967.

Brief background information

Salt	ATC	Formula	MM	CAS
-	N05C	C 9 H 17 NO	155.24 g / mol	512-48-1

Using

• hypnotic

Classes substance

• Amides

Synthesis Way

Synthesis of a)

Trade names

A country	Tradename	Manufacturer
Germany	Arantxa	Hoechst
	Betadorm-H	Woelm
	insomnia	ICN
	Nokturetten	Starke
	New Dolestan	Much
Ukraine	no	no

Formulations

• dragees 50 mg;
• 300 mg Tablets

References

• DRP 473 329 (IG Farben; appl 1925.).
• DRP 616 876 (IG Farben; appl 1930.).
• DRP 622 875 (IG Farben; appl 1931.).
• GB 253,950 (IG Farben; appl 1926;.. D-prior 1925).

1H NMR PREDICT