Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Methoxy-substituted 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives exhibit differential binding affinities at the 5-HT(2A) receptor. Bioorg Med Chem Lett 2008 Oct 01;18(19):5268-71

Date

09/09/2008

Pubmed ID

18774714

Pubmed Central ID

PMC3082371

DOI

10.1016/j.bmcl.2008.08.059

Scopus ID

2-s2.0-52249112061 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

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.

Author List

Dewkar GK, Peddi S, Mosier PD, Roth BL, Westkaemper RB

Author

Philip Mosier PhD Assistant Professor in the School of Pharmacy Administration department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Anthracenes
Combinatorial Chemistry Techniques
Humans
Models, Molecular
Molecular Structure
Receptor, Serotonin, 5-HT2A
Structure-Activity Relationship