title: Synthesis and biological evaluation of novel 5,8-disubstituted-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b] indoles as 5-HT(6) and H(1) receptors antagonists.
abstract: Synthesis, biological evaluation, and structure-activity relationships (SAR) for a series of novel gamma-carboline analogues of Dimebon are described. Among the studied compounds, tetrahydro-gamma-carboline 5b (2,8-dimethyl-5-[cis-2-pyridin-3-ylvinyl]-2,3,4,5-tetrahydro-carboline) has been identified as the most potent small molecule antagonist, in particular against histamine H(1) and serotonin 5-HT(6) receptors (IC(50) < 0.45 microM and IC(50) = 0.73 microM, respectively). A thorough comparative SAR study performed for the tested compounds has revealed significant correlations between the nature of side substituents and the related antagonistic activity.
authors.affiliation: Department of Organic Chemistry, Chemical Diversity Research Institute, Khimki, Moscow Reg, Russia. av@chemdiv.com
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Ivachtchenko
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Frolov
authors.forename: Oleg D
authors.initials: OD
authors.lastname: Mitkin
authors.forename: Volodymyr M
authors.initials: VM
authors.lastname: Kysil
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Khvat
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Tkachenko
mesh_terms: D002243:Carbolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D002243:Carbolines; D006634:Histamine H1 Antagonists; D007211:Indoles; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor; C010119:latrepirdine