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Discovery of 1-(3-{2-[4-(2-Methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)-2-imidazolidinone (GSK163090), a Potent, Selective, and Orally Active 5-HT(1A/B/D) Receptor Antagonist.
journal contribution
posted on 2023-06-07, 23:48 authored by Colin P Leslie, Matteo Biagetti, Silvia Bison, Steven M Bromidge, Romano Di Fabio, Daniele Donati, Alessandro Falchi, Martine J Garnier, Albert Jaxa-Chamiec, Gary Manchee, Giancarlo Merlo, Domenica A Pizzi, Luigi P Stasi, Jessica Tibasco, Antonio Vong, Simon E Ward, Laura ZonziniIn an effort to identify selective drug like pan-antagonists of the 5-HT(1) autoreceptors, studies were conducted to elaborate a previously reported dual acting 5-HT(1) antagonist/SSRI structure. A novel series of compounds was identified showing low intrinsic activities and potent affinities across the 5-HT(1A), 5-HT(1B), and 5-HT(1D) receptors as well as high selectivity against the serotonin transporter. From among these compounds, 1-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)-2-imidazolidinone (36) was found to combine potent in vivo activity with a strong preclinical developability profile, and on this basis it was selected as a drug candidate with the aim of assessing its potential as a fast-onset antidepressant/anxiolytic.
History
Publication status
- Published
Journal
Journal of Medicinal ChemistryISSN
0022-2623External DOI
Issue
23Volume
53Page range
8228-8240Pages
13.0Department affiliated with
- Chemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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