Ocinaplon

Ocinaplon
Clinical data
ATC code none
Identifiers
CAS Number 96604-21-6 YesY
PubChem (CID) 216456
IUPHAR/BPS 4277
ChemSpider 187602 YesY
UNII 2H6KVC5E76 YesY
KEGG D02617 YesY
Chemical and physical data
Formula C17H11N5O
Molar mass 301.302 g/mol
3D model (Jmol) Interactive image
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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]

Mechanism of action

The mechanism of action by which ocinaplon produces its anxiolytic effects is by modulating GABAA receptors,[2] although ocinaplon is more subtype-selective than most benzodiazepines.[3]

Availability

Development of ocinaplon is discontinued due to liver complications that occurred in one of the Phase III subjects.[4]

Synthesis

Ocinaplon synthesis: U.S. Patent 4,521,422 Further reading:[5][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 1129138Freely accessible.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ http://www.prnewswire.com/news-releases/dov-pharmaceutical-inc-places-ocinaplon-phase-iii-clinical-trial-on-hold-55011422.html
  5. ↑ 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 3817479Freely accessible. PMID 24204439.
  6. ↑ ARKIVOC 2010 (ii) 267-282
  7. ↑ a. Khalil, Mohamed; m. Sayed, Samia; a. Raslan, Mohamed (2012). "Heterocyclic Synthesis Via Enaminonitriles: One-Pot Synthesis of Some New Pyrazole, Pyrimidine, Pyrazolo[1,5-A]Pyrimidine and Pyrido[2,3-D]Pyrimidine Derivatives". American Journal of Organic Chemistry. 2 (6): 171. doi:10.5923/j.ajoc.20120206.07.
  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
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