Synthesis and biological evaluation of novel gamma-carboline analogues of Dimebon as potent 5-HT6 receptor antagonists.
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.
Ivachtchenko
Alexandre V
AV
Department of Organic Chemistry, Chemical Diversity Research Institute, 114401 Khimki, Moscow Reg., Russia. av@chemdiv.com
Frolov
Eugene B
EB
Mitkin
Oleg D
OD
Kysil
Volodymyr M
VM
Khvat
Alexander V
AV
Okun
Ilya M
IM
Tkachenko
Sergey E
SE
D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D011969:Receptors, Histamine H1 / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002243:Carbolines; D006634:Histamine H1 Antagonists; D007211:Indoles; D011969:Receptors, Histamine H1; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor; C055572:gamma-carboline; C010119:latrepirdine