Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents
dc.contributor.author | Cheng, J. | |
dc.contributor.author | Giguère, P. | |
dc.contributor.author | Onajole, O. | |
dc.contributor.author | Lv, W. | |
dc.contributor.author | Gaisin, A. | |
dc.contributor.author | Gunosewoyo, Hendra | |
dc.contributor.author | Schmerberg, C. | |
dc.contributor.author | Pogorelov, V. | |
dc.contributor.author | Rodriguiz, R. | |
dc.contributor.author | Vistoli, G. | |
dc.contributor.author | Wetsel, W. | |
dc.contributor.author | Roth, B. | |
dc.contributor.author | Kozikowski, A. | |
dc.date.accessioned | 2017-01-30T10:59:35Z | |
dc.date.available | 2017-01-30T10:59:35Z | |
dc.date.created | 2015-10-29T04:09:44Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Cheng, 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.uri | http://hdl.handle.net/20.500.11937/7396 | |
dc.identifier.doi | 10.1021/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.publisher | American Chemical Society | |
dc.title | Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents | |
dc.type | Journal Article | |
dcterms.source.volume | 58 | |
dcterms.source.number | 4 | |
dcterms.source.startPage | 1992 | |
dcterms.source.endPage | 2002 | |
dcterms.source.issn | 0022-2623 | |
dcterms.source.title | Journal of Medicinal Chemistry | |
curtin.department | School of Pharmacy | |
curtin.accessStatus | Fulltext not available |
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