9-(Aminomethyl)-9,10-dihydroanthracene is a novel and unlikely 5-HT2A receptor antagonist.
Structural elaboration of phenylethylamine to 9-(aminomethyl)-9,10-dihydroanthracene (AMDA) produces an agent with high affinity (Ki = 9.5-21 nM) at 5-HT2A receptors. It was shown that AMDA acts as a 5-HT2A receptor antagonist. The structure and molecular geometry of AMDA are not consistent with existing pharmacophore models for 5-HT2A receptor antagonist activity. Thus, AMDA may be a structurally novel parent of a new class of 5-HT2A receptor antagonists that binds to the receptor in a unique fashion that is distinct from the binding topology of existing 5-HT2A receptor antagonists.
Westkaemper
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RB
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298-0540, USA. richard.westkaemper@vcu.edu
Runyon
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SP
Bondarev
M L
ML
Savage
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JE
Roth
B L
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Glennon
R A
RA
D016475:3T3 Cells; D000818:Animals; D000873:Anthracenes / Q000737:chemistry / Q000378:metabolism*; D001667:Binding, Competitive; D007650:Ketanserin / Q000378:metabolism; D051379:Mice; D010636:Phenols / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011407:Propane / Q000031:analogs & derivatives / Q000378:metabolism; D011869:Radioligand Assay; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014316:Tritium
C121050:1,2,5-dimethoxy-4-bromophenol-2-aminopropane; C122082:9-(aminomethyl)-9,10-dihydroanthracene; D000873:Anthracenes; D010636:Phenols; D010716:Phosphatidylinositols; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014316:Tritium; D007650:Ketanserin; D011407:Propane