Solution Phase Parallel Synthesis of Substituted 3-Phenylsulfonyl-[1,2,3]triazolo[1,5-a]quinazolines: Selective Serotonin 5-HT6 Receptor Antagonists

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• 作者：Alexandre V. Ivachtchenko ; Elena S. Golovina ; Madina G. Kadieva ; Angela G. Koryakova ; Sergiy M. Kovalenko ; Oleg D. Mitkin ; Ilya M. Okun ; Irina M. Ravnyeyko ; Sergey E. Tkachenko ; Oleg V. Zaremba
• 刊名：Journal of Combinatorial Chemistry
• 出版年：2010
• 出版时间：July 12, 2010
• 年：2010
• 卷：12
• 期：4
• 页码：445-452
• 全文大小：401K
• 年卷期：v.12,no.4(July 12, 2010)
• ISSN：1520-4774

文摘

Here we present the solution phase parallel synthesis of a combinatorial library consisting of 776 new substituted 3-phenylsulfonyl-[1,2,3]triazolo[1,5-a]quinazolines and a study of the relation of their structure with a 5-HT₆ receptor antagonistic activity in a functional cell (HEK 293) analysis and radioligand competitive binding. We have found highly active and selective 5-HT₆R antagonists. The most active 5-HT₆R antagonists have IC₅₀ <100 nM in a functional assay, and K_i <10 nM in a binding assay, which is 100 times higher than the activity with respect to other serotonin receptors.