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

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

  • Eur J Med Chem. 2010 Feb;45(2):782-9. doi: 10.1016/j.ejmech.2009.10.035.
Alexandre V Ivachtchenko 1,  Oleg D Mitkin,  Sergey E Tkachenko,  Ilya M Okun,  Volodymyr M Kysil
Affiliations

Affiliation

  • 1 Department of Organic Chemistry, Chemical Diversity Research Institute, 114401 Khimki, Moscow Reg, Russia. av@chemdiv.com
PMID: 19939513 DOI: 10.1016/j.ejmech.2009.10.035
Abstract

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-HT(6) 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-HT(6) receptor antagonists with K(i) values equal to 2.1 nM and 5.7 nM and IC(50) 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.

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