N-Arylalkyl-2-azaadamantanes as cage-expanded polycarbocyclic sigma (σ) receptor ligands

被引：24

作者：

Banister, Samuel D. ^{[1
]}

Yoo, David T. ^{[1
]}

Chua, Sook Wern ^{[2
]}

Cui, Jinquan ^{[3
]}

Mach, Robert H. ^{[3
]}

Kassiou, Michael ^{[1
,2
,4
]}

机构：

[1] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia

[2] Brain & Mind Res Inst, Sydney, NSW 2050, Australia

[3] Washington Univ, Sch Med, Dept Radiol, Div Radiol Sci, St Louis, MO 63110 USA

[4] Univ Sydney, Discipline Med Radiat Sci, Sydney, NSW 2006, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 18期

关键词：

Adamantanes; Polycarbocyclic; Sigma receptors; CNS; Structure-activity relationships; STRIATAL SLICES; BINDING; MODULATION; RELEASE; EXPRESSION; SIGMA-1-RECEPTOR; TRISHOMOCUBANES; AFFINITY; CLONING; CA2+;

D O I：

10.1016/j.bmcl.2011.07.028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of racemic N-arylalkyl-2-azaadamantan-1-ols (9-15) and the corresponding deoxygenated, achiral N-arylalkyl-2-azaadamantanes (23-29) were synthesized and screened in competition binding assays against a panel of CNS targets. Adamantyl hemiaminals 9-15 displayed generally low affinity for both sigma(1) (K-i values = 294-1950 nM) and sigma(2) receptors (K-i values = 201-1020 nM), and negligible affinity for 42 other CNS proteins. Deoxygenation of 9-15 to give the corresponding achiral azaadamantanes 23-29 greatly improved affinity for sigma(1) (K-i values = 8.3-239 nM) and sigma(2) receptors (K-i values = 34-312 nM). (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：5289 / 5292

页数：4

共 36 条

[1] Effect of ploidy, recruitment, environmental factors, and tamoxifen treatment on the expression of sigma-2 receptors in proliferating and quiescent tumour cells [J].

Al-Nabulsi, I ;

Mach, RH ;

Wang, LM ;

Wallen, CA ;

Keng, PC ;

Sten, K ;

Childers, SR ;

Wheeler, KT .

BRITISH JOURNAL OF CANCER, 1999, 81 (06) :925-933

[2] The sigma receptor as a ligand-regulated auxiliary potassium channel subunit [J].

Aydar, E ;

Palmer, CP ;

Klyachko, VA ;

Jackson, MB .

NEURON, 2002, 34 (03) :399-410

[3] Molecular hybridization of 4-azahexacyclo[5.4.1.02,6.03,10.05,9.08,11] dodecane-3-ol with sigma (σ) receptor ligands modulates off-target activity and subtype selectivity [J].

Banister, Samuel D. ;

Moussa, Iman A. ;

Jorgensen, William T. ;

Chua, Sook Wern ;

Kassiou, Michael .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (12) :3622-3626

[4] Trishomocubane as a scaffold for the development of selective dopamine transporter (DAT) ligands [J].

Banister, Samuel D. ;

Moussa, Iman A. ;

Beinat, Corinne ;

Reynolds, Aaron J. ;

Schiavini, Paolo ;

Jorgensen, William T. ;

Kassiou, Michael .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (01) :38-41

[5] Oxo-bridged isomers of aza-trishomocubane sigma (σ) receptor ligands: Synthesis, in vitro binding, and molecular modeling [J].

Banister, Samuel D. ;

Moussa, Iman A. ;

Jordan, Meredith J. T. ;

Coster, Mark J. ;

Kassiou, Michael .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (01) :145-148

[6] The role of sigma receptors in depression [J].

Bermack, JE ;

Debonnel, G .

JOURNAL OF PHARMACOLOGICAL SCIENCES, 2005, 97 (03) :317-336

[7] Modulation of serotonergic neurotransmission by short- and long-term treatments with sigma ligands [J].

Bermack, JE ;

Debonnel, G .

BRITISH JOURNAL OF PHARMACOLOGY, 2001, 134 (03) :691-699

[8] Modulation of NMDA and dopaminergic neurotransmissions by sigma ligands: Possible implications for the treatment of psychiatric disorders [J].

Debonnel, G ;

deMontigny, C .

LIFE SCIENCES, 1996, 58 (09) :721-734

[9] Pharmacophore identification for sigma-1 (σ1) receptor binding:: Application of the "deconstruction reconstruction elaboration" approach [J].

Glennon, RA .

MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2005, 5 (10) :927-940

[10] Release of [H-3]dopamine from guinea pig striatal slices is modulated by sigma(1) receptor agonists [J].

Gonzalez, GM ;

Werling, LL .

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1997, 356 (04) :455-461

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