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.

Leslie, Colin P, Biagetti, Matteo, Bison, Silvia, Bromidge, Steven M, Di Fabio, Romano, Donati, Daniele, Falchi, Alessandro, Garnier, Martine J, Jaxa-Chamiec, Albert, Manchee, Gary, Merlo, Giancarlo, Pizzi, Domenica A, Stasi, Luigi P, Tibasco, Jessica, Vong, Antonio, Ward, Simon E and Zonzini, Laura (2010) 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 of Medicinal Chemistry, 53 (23). pp. 8228-8240. ISSN 0022-2623

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Abstract

In 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science
Depositing User: EPrints Services
Date Deposited: 06 Feb 2012 19:43
Last Modified: 06 Mar 2017 00:43
URI: http://sro.sussex.ac.uk/id/eprint/21877

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