【文章名】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
作者
LESLIE COLIN P; BIAGETTI MATTEO; BISON SILVIA; BROMIDGE STEVEN M; DI FABIO ROMANO; DONATI DANIELE; FALCHI ALESSANDRO; GARNIER MARTINE J; JAXACHAMIEC ALBERT; MANCHEE GARY; MERLO GIANCARLO; PIZZI DOMENICA A; STASI LUIGI P; TIBASCO JESSICA; VONG ANTONIO; WARD SIMON E; ZONZINI LAURA
[摘要]：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-imidazo lidinone (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.
