Synthesis and biological evaluation of novel gamma-carboline analogues of Dimebon as potent 5-HT6 receptor antagonists

Alexandre V Ivachtchenko; Eugene B Frolov; Oleg D Mitkin; Volodymyr M Kysil; Alexander V Khvat; Ilya M Okun; Sergey E Tkachenko

doi:10.1016/j.bmcl.2009.04.128

Synthesis and biological evaluation of novel gamma-carboline analogues of Dimebon as potent 5-HT6 receptor antagonists

Bioorg Med Chem Lett. 2009 Jun 15;19(12):3183-7. doi: 10.1016/j.bmcl.2009.04.128. Epub 2009 May 3.

Authors

Alexandre V Ivachtchenko¹, Eugene B Frolov, Oleg D Mitkin, Volodymyr M Kysil, Alexander V Khvat, Ilya M Okun, Sergey E Tkachenko

Affiliation

¹ Department of Organic Chemistry, Chemical Diversity Research Institute, 114401 Khimki, Moscow Reg., Russia. av@chemdiv.com

PMID: 19443217
DOI: 10.1016/j.bmcl.2009.04.128

Abstract

Synthesis, biological evaluation and structure-activity relationships for a series of novel gamma-carboline analogues of Dimebon are described. Among the studied compounds, gamma-carbolines 3{8} and 3{14} have been identified as potent small molecule antagonists of histamine H(1) (IC(50)=0.1 microM) and serotonin 5-HT(6) (IC(50)=0.37 microM) receptors, respectively.

MeSH terms

Carbolines / chemical synthesis
Carbolines / chemistry*
Carbolines / pharmacology
Cell Line
Histamine H1 Antagonists / chemical synthesis
Histamine H1 Antagonists / chemistry
Histamine H1 Antagonists / pharmacology
Humans
Indoles / chemistry
Inhibitory Concentration 50
Receptors, Histamine H1 / drug effects
Receptors, Serotonin / drug effects*
Serotonin Antagonists / chemical synthesis
Serotonin Antagonists / chemistry*
Serotonin Antagonists / pharmacology
Structure-Activity Relationship

Substances

Carbolines
Histamine H1 Antagonists
Indoles
Receptors, Histamine H1
Receptors, Serotonin
Serotonin Antagonists
serotonin 6 receptor
gamma-carboline
latrepirdine