Methoxy-substituted 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives exhibit differential binding affinities at the 5-HT(2A) receptor.
The effects of methoxy-substitution at the 1-, 2-, 3-, and 4-positions of 9-aminomethyl-9,10-dihydroanthracene (AMDA) on h5-HT(2A) receptor affinity were determined. Racemic mixtures of these compounds were found to show the following affinity trend: 3-MeO > 4-MeO > 1-MeO approximately 2-MeO. Comparison of the effects of these substitutions, with the aid of computational molecular modeling techniques, suggest that the various positional and stereochemical isomers of the methoxy-substituted AMDA compounds interact differently with the h5-HT(2A) receptor. It is predicted that for the compounds with higher affinities, the methoxy oxygen atom is able to interact with hydrogen bond-donating sidechains within alternative h5-HT(2A) receptor binding sites, whereas the lower-affinity isomers lack this ability.
Dewkar
Gajanan K
GK
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 410 N. 12th Street, PO Box 980540, Richmond, VA 23298-0540, USA.
Peddi
Srinivas
S
Mosier
Philip D
PD
Roth
Bryan L
BL
Westkaemper
Richard B
RB
D000873:Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D013329:Structure-Activity Relationship
C122082:9-(aminomethyl)-9,10-dihydroanthracene; D000873:Anthracenes; D044402:Receptor, Serotonin, 5-HT2A
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