Synthesis and biological activity of 5-styryl and 5-phenethyl-substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles.
Syntheses, biological evaluation, and structure-activity relationships for a series of novel 5-styryl and 5-phenethyl analogs of dimebolin are disclosed. The novel derivatives and dimebolin share a broad spectrum of activities against therapeutically relevant targets. Among all synthesized derivatives, 2,8-dimethyl-5-[(Z)-2-phenylvinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole and its 5-phenethyl analog are the most potent blockers of 5-HT(7), 5-HT(6), 5-HT(2C), Adrenergic alpha(2) and H(1) receptors. The general affinity rank order towards the studied receptors was Z-3(2)>4(2)4(3)>>dimebolin, all of them having highest affinities to 5-HT(7) receptors.
Ivachtchenko
Alexandre V
AV
Department of Organic Chemistry, Chemical Diversity Research Institute, 114401 Khimki, Moscow Reg, Russia. av@chemdiv.com
Frolov
Eugen B
EB
Mitkin
Oleg D
OD
Tkachenko
Sergei E
SE
Okun
Ilya M
IM
Khvat
Alex V
AV
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / 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 / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000737:chemistry / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists; D013329:Structure-Activity Relationship
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D006634:Histamine H1 Antagonists; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; D018341:Receptors, Adrenergic, alpha-2; D011969:Receptors, Histamine H1; D011985:Receptors, Serotonin; D058830:Serotonin 5-HT2 Receptor Antagonists; C097216:serotonin 6 receptor; C104425:serotonin 7 receptor; C010119:latrepirdine