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]
A 2019 review found tentative evidence of benefit in anxiety.[2]
Mechanism of actionedit
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]
Availabilityedit
Development of ocinaplon is discontinued due to liver complications that occurred in one of the Phase III subjects.[5]
Synthesisedit
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).
Referencesedit
^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. PMC1129138. 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.
^. 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. PMC3817479. PMID 24204439.
ocinaplon, anxiolytic, drug, pyrazolopyrimidine, family, drugs, other, pyrazolopyrimidine, drugs, include, zaleplon, indiplon, clinical, dataatc, codenoneidentifiersiupac, name, pyridin, pyridin, ylpyrazolo, pyrimidin, methanonecas, number96604, ypubchem, cid2. Ocinaplon is an anxiolytic drug in the pyrazolopyrimidine family of drugs Other pyrazolopyrimidine drugs include zaleplon and indiplon OcinaplonClinical dataATC codenoneIdentifiersIUPAC name pyridin 2 yl 7 pyridin 4 ylpyrazolo 1 5 a pyrimidin 3 yl methanoneCAS Number96604 21 6 YPubChem CID216456IUPHAR BPS4277ChemSpider187602 YUNII2H6KVC5E76KEGGD02617 YCompTox Dashboard EPA DTXSID00242362Chemical and physical dataFormulaC 17H 11N 5OMolar mass301 309 g mol 13D model JSmol Interactive imageSMILES O C c1cnn2c ccnc12 c3ccncc3 c4ncccc4InChI 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 YKey OQJFBUOFGHPMSR UHFFFAOYSA N Y verify 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 Contents 1 Medical uses 2 Mechanism of action 3 Availability 4 Synthesis 5 ReferencesMedical uses editA 2019 review found tentative evidence of benefit in anxiety 2 Mechanism of action editThe 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 editDevelopment of ocinaplon is discontinued due to liver complications that occurred in one of the Phase III subjects 5 Synthesis edit nbsp 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 edit 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 Retrieved from https en wikipedia org w index php title Ocinaplon amp oldid 1191998792, wikipedia, wiki, book, books, library,
