2. Academic Validation
  3. Discovery of 1-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)-2-imidazolidinone (GSK163090), a Potent, selective, and orally active 5-HT1A/B/D receptor antagonist

Discovery of 1-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)-2-imidazolidinone (GSK163090), a Potent, selective, and orally active 5-HT1A/B/D receptor antagonist

  • J Med Chem. 2010 Dec 9;53(23):8228-40. doi: 10.1021/jm100714c.
Colin P Leslie 1,  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 Zonzini
Affiliations

Affiliation

  • 1 Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline SpA, Medicines Research Centre, Via A. Fleming 4, 37135 Verona, Italy.
PMID: 21053897 DOI: 10.1021/jm100714c
Abstract

In an effort to identify selective drug like pan-antagonists of the 5-HT1 autoreceptors, studies were conducted to elaborate a previously reported dual acting 5-HT1 antagonist/SSRI structure. A novel series of compounds was identified showing low intrinsic activities and potent affinities across the 5-HT1A, 5-HT1B, and 5-HT1D 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.

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