Ocinaplon ATC code
pyridin-2-yl-(7-pyridin-4-ylpyrazolo[1,5-a]pyrimidin-3-yl)methanone
CAS Number PubChem CID IUPHAR/BPS ChemSpider UNII KEGG CompTox Dashboard (EPA ) Formula C 17 H 11 N 5 O Molar mass 301.309 g·mol−1 3D model (JSmol )
O=C(c1cnn2c(ccnc12)c3ccncc3)c4ncccc4
InChI=1S/C17H11N5O/c23-16(14-3-1-2-7-19-14)13-11-21-22-15(6-10-20-17(13)22)12-4-8-18-9-5-12/h1-11H
Y Key:OQJFBUOFGHPMSR-UHFFFAOYSA-N
Y
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 [ ]
Condensation of [8] with N,N-Dimethylformamide dimethyl acetal () 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 [ ]
^ 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 .
^ 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 . S2CID 72332967 .
^ 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 . S2CID 21913400 .
^ 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 . S2CID 22793644 .
^ "DOV Pharmaceutical, Inc. Places Ocinaplon Phase III Clinical Trial On Hold" . PR NewsWire . Archived from the original on 4 March 2016.
^ 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 .
^ ARKIVOC 2010 (ii) 267-282
^ 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 .
^ U.S. Patent 4,900,836
^ CA 1243029
Anxiolytics (N05B )
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‡ Withdrawn from market
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§ Never to phase III
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Org 25,435
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See also: Receptor/signaling modulators • GABA receptor modulators • GABA metabolism/transport modulators