Thozalinone

Thozalinone (USAN) (brand name Stimsen; former developmental code name CL-39808) is a psychostimulant that has been used as an antidepressant in Europe.^[1]^[2]^[3]^[4]^[5] It has also been trialed as an anorectic.^[6] Thozalinone is described as a "dopaminergic stimulant",^[7] and likely acts via inducing the release of dopamine and to a minimal extent norepinephrine; similar to analogue pemoline, it is reportedly devoid of abuse potential unlike most other dopaminergic psychostimulants.^[2]^[7]^[8]

Other namesTozalinone, Thozalinon

Routes of
administrationOral

ATC code

none

Legal status

In general: ℞ (Prescription only)

Quick facts Clinical data, Other names ...

Thozalinone
Clinical data


Other names	Tozalinone, Thozalinon
Routes of administration	Oral
ATC code	none
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name (RS)-2-(Dimethylamino)-5-phenyl-1,3-oxazol-4(5H)-one
CAS Number	655-05-0^N
PubChem CID	12602
ChemSpider	12082^Y
UNII	68X5932947
KEGG	D06115^Y
ChEMBL	ChEMBL2105457
CompTox Dashboard (EPA)	DTXSID70862359
Chemical and physical data
Formula	C₁₁H₁₂N₂O₂
Molar mass	204.229 g·mol⁻¹
3D model (JSmol)	Interactive image
Chirality	Racemic mixture
SMILES O=C2\N=C(/OC2c1ccccc1)N(C)C
InChI InChI=1S/C11H12N2O2/c1-13(2)11-12-10(14)9(15-11)8-6-4-3-5-7-8/h3-7,9H,1-2H3^Y Key:JJSHYECKYLDYAR-UHFFFAOYSA-N^Y
^NY (what is this?) (verify)

Synthesis

Sodium hydride is used as a strong base to abstract the alcohol proton in ethyl mandelate [774-40-3] (1); addition of this alkoxide to dimethylcyanamide [1467-79-4] gives the intermediate (2). Intramolecular cyclization then occurs giving Thozalinone (3).

Notes

In treatment of Parkinsonism: W. D. Gray, C. E. Edward, U.S. patent 3,665,075 (1972 to Am. Cyanamid).
Pharmacological studies:^[11]

References

[1]
Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 435–. ISBN 978-1-4757-2085-3.
[2]
Greenblatt EN, Osterberg AC (July 1965). "Some pharmacologic properties of thozalinone, a new excitant". Toxicology and Applied Pharmacology. 7 (4): 566–78. doi:10.1016/0041-008X(65)90042-6. PMID 4378772.
[3]
Dictionary of organic compounds. London: Chapman & Hall. 1996. ISBN 0-412-54090-8. Archived from the original on 2021-05-31. Retrieved 2021-05-31.
[4]
Merck index on CD-ROM: Windows. London: Chapman & Hall EPD. 1998. ISBN 0-412-82910-X.
[5]
Gallant DM, Bishop MP, Scrignar CB, Hornsby L, Moore B, Inturrisi BB (December 1966). "A double-blind study of thozalinone (C1 39,808) in depressed outpatients". Current Therapeutic Research, Clinical and Experimental. 8 (12): 621–2. PMID 4962734.
[6]
Leite AC, Liepen LL, Costa VP (September 1971). "[Clinical trial of Stimsem Thozalinone in the treatment of obese patients]". Revista Brasileira de Medicina (in Portuguese). 28 (9): 475–8. PMID 5139648.
[7]
Yen-Koo HC, Balazs T (1980). "Detection of dopaminergic supersensitivity induced by neuroleptic drugs in mice". Drug and Chemical Toxicology. 3 (2): 237–47. doi:10.3109/01480548009108286. PMID 6112126.
[8]
Yen-Koo HC, Davis DA, Balazs T (1985). "Inhibition of dopaminergic agonist-induced gnawing behavior by neuroleptic drugs in mice". Drug and Chemical Toxicology. 8 (6): 495–502. doi:10.3109/01480548509041072. PMID 2868876.
[9]
Howell CF, Quinones NQ, Hardy Jr RA (May 1962). "2-Amino-2-oxazolin-4-ones. I. Synthesis". The Journal of Organic Chemistry. 27 (5): 1679–1685. doi:10.1021/jo01052a047.
[10]
Lindberg UH, Pedersen J (February 1968). "Compounds related to pemoline. 2-amino-5-aryl-4-oxo-2-oxazolines". Acta Pharmaceutica Suecica. 5 (1): 15–22. PMID 4386169.
[11]
Bernstein BM, Latimer CN (1968). "Behavioral facilitation: The interaction of imipramine and desipramine with amphetamine, alpha-pipradrol, methylphenidate, and thozalinone". Psychopharmacologia. 12 (4): 338–345. doi:10.1007/BF00401412. PMID 4385109. S2CID 31096140.

Synthesis

Notes

See also

References

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