Abstract
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.
Copyright 2009 Elsevier Ltd. All rights reserved.
MeSH terms
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Adrenergic alpha-2 Receptor Antagonists
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Adrenergic alpha-Antagonists / chemical synthesis*
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Adrenergic alpha-Antagonists / chemistry
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Adrenergic alpha-Antagonists / pharmacology
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Cell Line
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Histamine H1 Antagonists / chemical synthesis*
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Histamine H1 Antagonists / chemistry
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Histamine H1 Antagonists / pharmacology
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Humans
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Receptor, Serotonin, 5-HT2C / metabolism
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Receptors, Adrenergic, alpha-2 / metabolism
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Receptors, Histamine H1 / chemistry
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Receptors, Histamine H1 / metabolism
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Receptors, Serotonin / chemistry
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Receptors, Serotonin / metabolism
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Serotonin 5-HT2 Receptor Antagonists
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Structure-Activity Relationship
Substances
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Adrenergic alpha-2 Receptor Antagonists
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Adrenergic alpha-Antagonists
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Histamine H1 Antagonists
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Indoles
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Receptor, Serotonin, 5-HT2C
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Receptors, Adrenergic, alpha-2
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Receptors, Histamine H1
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Receptors, Serotonin
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Serotonin 5-HT2 Receptor Antagonists
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serotonin 6 receptor
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serotonin 7 receptor
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latrepirdine