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dc.contributor.authorCheng, J.
dc.contributor.authorGiguère, P.
dc.contributor.authorOnajole, O.
dc.contributor.authorLv, W.
dc.contributor.authorGaisin, A.
dc.contributor.authorGunosewoyo, Hendra
dc.contributor.authorSchmerberg, C.
dc.contributor.authorPogorelov, V.
dc.contributor.authorRodriguiz, R.
dc.contributor.authorVistoli, G.
dc.contributor.authorWetsel, W.
dc.contributor.authorRoth, B.
dc.contributor.authorKozikowski, A.
dc.date.accessioned2017-01-30T10:59:35Z
dc.date.available2017-01-30T10:59:35Z
dc.date.created2015-10-29T04:09:44Z
dc.date.issued2015
dc.date.submitted2015-10-29
dc.identifier.citationCheng, J. and Giguère, P. and Onajole, O. and Lv, W. and Gaisin, A. and Gunosewoyo, H. and Schmerberg, C. et al. 2015. Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents. Journal of Medicinal Chemistry. 58 (4): pp. 1992-2002.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/7396
dc.identifier.doi10.1021/jm5019274
dc.description.abstract

The discovery of a new series of compounds that are potent, selective 5-HT2C receptor agonists is described herein as we continue our efforts to optimize the 2-phenylcyclopropylmethylamine scaffold. Modifications focused on the alkoxyl substituent present on the aromatic ring led to the identification of improved ligands with better potency at the 5-HT2C receptor and excellent selectivity against the 5-HT2A and 5-HT2B receptors. ADMET studies coupled with a behavioral test using the amphetamine-induced hyperactivity model identified four compounds possessing drug-like profiles and having antipsychotic properties. Compound (+)-16b, which displayed an EC50 of 4.2 nM at 5-HT2C, no activity at 5-HT2B, and an 89-fold selectivity against 5-HT2A, is one of the most potent and selective 5-HT2C agonists reported to date. The likely binding mode of this series of compounds to the 5-HT2C receptor was also investigated in a modeling study, using optimized models incorporating the structures of β2-adrenergic receptor and 5-HT2B receptor.

dc.publisherAmerican Chemical Society
dc.titleOptimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents
dc.typeJournal Article
dcterms.dateSubmitted2015-10-29
dcterms.source.volume58
dcterms.source.number4
dcterms.source.startPage1992
dcterms.source.endPage2002
dcterms.source.issn0022-2623
dcterms.source.titleJournal of Medicinal Chemistry
curtin.digitool.pid232557
curtin.pubStatusPublished
curtin.refereedTRUE
curtin.departmentSchool of Pharmacy
curtin.identifier.scriptidPUB-VC-ORD-SA-15864
curtin.identifier.elementsidELEMENTS-68753
curtin.accessStatusFulltext not available


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