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9-Aminomethyl-9,10-dihydroanthracene (AMDA) analogs as structural probes for steric tolerance in 5-HT2A and H1 receptor binding sites. Bioorg Med Chem Lett 2010 Feb 01;20(3):935-8



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Scopus ID

2-s2.0-74049127386 (requires institutional sign-in at Scopus site)   6 Citations


Synthesis, radioligand binding and molecular modeling studies of several 9-aminomethyl-9,10-dihydroanthracene (AMDA) analogs were carried out to determine the extent of the steric tolerance associated with expansion of the tricyclic ring system and amine substitution at 5-HT(2A) and H(1) receptors. A mixture of (7,12-dihydrotetraphene-12-yl)methanamine and (6,11-dihydrotetracene-11-yl)methanamine in a 75-25% ratio was found to have an apparent K(i) of 10nM at the 5-HT(2A) receptor. A substantial binding affinity for (7,12-dihydrotetraphene-3-methoxy-12-yl)methanamine at the 5-HT(2A) receptor (K(i)=21 nM) was also observed. Interestingly, this compound was found to have 100-fold selectivity for 5-HT(2A) over the H(1) receptor (K(i)=2500 nM). N-Phenylalkyl-AMDA derivatives, in which the length of the alkyl chain varied from methylene to n-butylene, were found to have only weak affinity for both 5-HT(2A) and H(1) receptors (K(i)=223 to 964 nM). Our results show that large rigid annulated AMDA analogs can be sterically accommodated within the proposed 5-HT(2A) binding site.

Author List

Shah JR, Mosier PD, Peddi S, Roth BL, Westkaemper RB


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

Binding Sites
Receptor, Serotonin, 5-HT2A
Receptors, Serotonin, 5-HT1
Structure-Activity Relationship