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甲氧基取代的9-氨甲基-9,10-二氢蒽（AMDA）衍生物在5-羟色胺（2A）受体上表现出不同的结合亲和力。

Methoxy-substituted 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives exhibit differential binding affinities at the 5-HT(2A) receptor.

作者信息

Dewkar Gajanan K, Peddi Srinivas, Mosier Philip D, Roth Bryan L, Westkaemper Richard B

机构信息

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 410 N. 12th Street, PO Box 980540, Richmond, VA 23298-0540, USA.

出版信息

Bioorg Med Chem Lett. 2008 Oct 1;18(19):5268-71. doi: 10.1016/j.bmcl.2008.08.059. Epub 2008 Aug 22.

DOI:10.1016/j.bmcl.2008.08.059
PMID:18774714
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3082371/
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.

摘要

测定了9-氨甲基-9,10-二氢蒽（AMDA）的1-、2-、3-和4-位甲氧基取代对h5-HT(2A)受体亲和力的影响。发现这些化合物的外消旋混合物呈现以下亲和力趋势：3-甲氧基＞4-甲氧基＞1-甲氧基≈2-甲氧基。借助计算分子建模技术对这些取代作用的影响进行比较，结果表明甲氧基取代的AMDA化合物的各种位置和立体化学异构体与h5-HT(2A)受体的相互作用方式不同。据预测，对于具有较高亲和力的化合物，甲氧基氧原子能够与h5-HT(2A)受体不同结合位点内的氢键供体侧链相互作用，而亲和力较低的异构体则缺乏这种能力。

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本文引用的文献

1
Multistructure 3D-QSAR studies on a series of conformationally constrained butyrophenones docked into a new homology model of the 5-HT2A receptor.
J Med Chem. 2007 Jul 12;50(14):3242-55. doi: 10.1021/jm070277a. Epub 2007 Jun 19.
2
Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists.
Mol Pharmacol. 2006 Dec;70(6):1956-64. doi: 10.1124/mol.106.028720. Epub 2006 Sep 25.
3
Identification of amino acid residues important for sarpogrelate binding to the human 5-hydroxytryptamine2A serotonin receptor.
J Pharmacol Sci. 2006 Sep;102(1):55-63. doi: 10.1254/jphs.fp0060171. Epub 2006 Sep 15.
4
QF2004B, a potential antipsychotic butyrophenone derivative with similar pharmacological properties to clozapine.
Neuropharmacology. 2006 Aug;51(2):251-62. doi: 10.1016/j.neuropharm.2006.03.021. Epub 2006 May 11.
5
Multiple sequence alignment with the Clustal series of programs.
Nucleic Acids Res. 2003 Jul 1;31(13):3497-500. doi: 10.1093/nar/gkg500.
6
A homology-based model of the human 5-HT2A receptor derived from an in silico activated G-protein coupled receptor.
J Comput Aided Mol Des. 2002 Jul;16(7):511-20. doi: 10.1023/a:1021275430021.
7
Protein-based virtual screening of chemical databases. II. Are homology models of G-Protein Coupled Receptors suitable targets?
Proteins. 2003 Jan 1;50(1):5-25. doi: 10.1002/prot.10237.
8
Application of ligand SAR, receptor modeling and receptor mutagenesis to the discovery and development of a new class of 5-HT(2A) ligands.
Curr Top Med Chem. 2002 Jun;2(6):575-98. doi: 10.2174/1568026023393741.
9
Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene.
Bioorg Med Chem Lett. 2001 Mar 12;11(5):655-8. doi: 10.1016/s0960-894x(01)00023-3.
10
Exploring the relationship between binding modes of 9-(aminomethyl)-9,10-dihydroanthracene and cyproheptadine analogues at the 5-HT2A serotonin receptor.
Bioorg Med Chem Lett. 2001 Feb 26;11(4):563-6. doi: 10.1016/s0960-894x(01)00010-5.

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