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Ocinaplon

Ocinaplon
Ocinaplon.svg
Clinical data
ATC code
  • none
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H11N5O
Molar mass301.302 g/mol g·mol−1
3D model (JSmol)
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Ocinaplon is an anxiolytic drug in the pyrazolopyrimidine family of drugs. Other pyrazolopyrimidine drugs include zaleplon and indiplon.

Ocinaplon has a similar pharmacological profile to the benzodiazepine family of drugs, but with mainly anxiolytic properties and relatively little sedative or amnestic effect.[1]

Medical uses

A 2019 review found tentative evidence of benefit in anxiety.[2]

Mechanism of action

The mechanism of action by which ocinaplon produces its anxiolytic effects is by modulating GABAA receptors,[3] although ocinaplon is more subtype-selective than most benzodiazepines.[4]

Availability

Development of ocinaplon is discontinued due to liver complications that occurred in one of the Phase III subjects.[5]

Synthesis

Ocinaplon synthesis: U.S. Patent 4,521,422 Further reading:[6][7]

Condensation of 4-Acetylpyridine[8] with N,N-Dimethylformamide dimethyl acetal (DMFDMA) gives the "enamide" (3). This is then condensed with (3-Amino-1H-pyrazol-4-yl)(2-pyridinyl)methanone (4) (96219-90-8).[9][10] This is the same intermediate as was used in the synthesis of zaleplon in which the nitrile is replaced by a 2-acetylpyridil moiety. This affords the anxiolytic agent ocinaplon (5).

References

  1. ^ Lippa, A; Czobor, P; Stark, J; Beer, B; Kostakis, E; Gravielle, M; Bandyopadhyay, S; Russek, S. J.; Gibbs, T. T.; Farb, D. H.; Skolnick, P (2005). "Selective anxiolysis produced by ocinaplon, a GABAA receptor modulator". Proceedings of the National Academy of Sciences. 102 (20): 7380–7385. doi:10.1073/pnas.0502579102. PMC 1129138. PMID 15870187.
  2. ^ Slee, April; Nazareth, Irwin; Bondaronek, Paulina; Liu, Yifeng; Cheng, Zhihang; Freemantle, Nick (February 2019). "Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis". The Lancet. 393 (10173): 768–777. doi:10.1016/S0140-6736(18)31793-8.
  3. ^ Mirza, N. R.; Rodgers, R. J.; Mathiasen, L. S. (2006). "Comparative cue generalization profiles of L-838, 417, SL651498, zolpidem, CL218,872, ocinaplon, bretazenil, zopiclone, and various benzodiazepines in chlordiazepoxide and zolpidem drug discrimination". Journal of Pharmacology and Experimental Therapeutics. 316 (3): 1291–9. doi:10.1124/jpet.105.094003. PMID 16339395.
  4. ^ Atack, J. R. (2005). "The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics". Expert Opinion on Investigational Drugs. 14 (5): 601–18. doi:10.1517/13543784.14.5.601. PMID 15926867.
  5. ^ [www.prnewswire.com]
  6. ^ Baumann, Marcus; Baxendale, Ian R (2013). "An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles". Beilstein Journal of Organic Chemistry. 9: 2265–319. doi:10.3762/bjoc.9.265. PMC 3817479. PMID 24204439.
  7. ^ ARKIVOC 2010 (ii) 267-282
  8. ^ "A-Amino Acetals: 2,2-Diethoxy-2-(4-Pyridyl)Ethylamine". Organic Syntheses. 64: 19. 1986. doi:10.15227/orgsyn.064.0019.
  9. ^ U.S. Patent 4,900,836
  10. ^ CA 1243029