Synthesis and SAR of highly potent dual 5-HT1A and 5-HT1B antagonists as potential antidepressant drugs期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

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Synthesis and SAR of highly potent dual 5-HT1A and 5-HT1B antagonists as potential antidepressant drugs

Authors:	Kling Andreas Lange Udo E W Mack Helmut Bakker Margot H M Drescher Karla U Hornberger Wilfried Hutchins Charles W Möller Achim Müller Reinhold Schmidt Martin Unger Liliane Wicke Karsten Schellhaas Kurt Steiner Gerd

Institution:	^aNeuroscience Discovery, Abbott GmbH & Co. KG, D-67008 Ludwigshafen, Germany ^bAdvanced Technologies, Abbott Laboratories, Abbott Park, IL 60064-6101, USA ^cBASF AG, D-67056 Ludwigshafen, Germany

Abstract:	Novel 5-HT₁ autoreceptor ligands based on the N-4-aryl-piperazinyl-N′-ethyl-5,6,7,8-tetrahydropyrido4′, 3′:4,5]thieno2,3-d]pyrimidin-4(3H)-one core are described. Aiming at antidepressants with a novel mode of action our objective was to identify potent antagonists showing balanced affinities and high selectivity for the 5-HT_1A and 5-HT_1B receptors. Strategies for the development of dual 5-HT_1A and 5-HT_1B antagonists based on 1 and 2 as leads and the corresponding results are discussed. Isoquinoline analogue 33 displayed high affinity and an antagonistic mode of action for the 5-HT_1A and the 5-HT_1B receptors and was characterized further with respect to selectivity, electrically stimulated ³H]5-HT release and in vivo efficacy.

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