8-Sulfonyl-substituted tetrahydro-1H-pyrido[4,3-b]indoles as 5-HT6 receptor antagonists

A series of novel 8-sulfonyl-substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles (THPI) has been synthesized and their ability to interact with 5-HT6 receptors evaluated in cell-based and radioligand binding assays. Amongst evaluated THPIs, compounds 9.HCl and 20.HCl have been identified as the most potent 5-HT6 receptor antagonists with Ki values equal to 2.1 nM and 5.7 nM and IC50 values (functional assay) equal to 15 nM and 78 nM, respectively. Affinities of these two compounds for several serotonin receptors in the competitive radioligand binding assays as well as their specificity profiles against a panel of therapeutic targets have been determined.

Graphical abstractA series of novel 8-sulfonyl-substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles has been synthesized and evaluated as antagonists of 5-HT6 receptors.Figure optionsDownload full-size imageDownload as PowerPoint slide