Ocinaplon

Ocinaplon is an anxiolytic drug in the pyrazolopyrimidine family of drugs. Other pyrazolopyrimidine drugs include zaleplon and indiplon.

Ocinaplon
Clinical data
ATC code
  • none
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H11N5O
Molar mass301.309 g·mol−1
3D model (JSmol)
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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, et al. (May 2005). "Selective anxiolysis produced by ocinaplon, a GABA(A) receptor modulator". Proceedings of the National Academy of Sciences of the United States of America. 102 (20): 7380–5. Bibcode:2005PNAS..102.7380L. doi:10.1073/pnas.0502579102. PMC 1129138. PMID 15870187.
  2. Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N (February 2019). "Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis". Lancet. 393 (10173): 768–777. doi:10.1016/S0140-6736(18)31793-8. PMID 30712879.
  3. Mirza NR, Rodgers RJ, Mathiasen LS (March 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". The Journal of Pharmacology and Experimental Therapeutics. 316 (3): 1291–9. doi:10.1124/jpet.105.094003. PMID 16339395.
  4. Atack JR (May 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. "DOV Pharmaceutical, Inc. Places Ocinaplon Phase III Clinical Trial On Hold". PR NewsWire. Archived from the original on 4 March 2016.
  6. Baumann M, Baxendale IR (October 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. LaMattina JL, Sulesk RT (1986). "A-Amino Acetals: 2,2-Diethoxy-2-(4-Pyridyl)Ethylamine". Organic Syntheses. 64: 19. doi:10.15227/orgsyn.064.0019.
  9. U.S. Patent 4,900,836
  10. CA 1243029
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