Pyrazino[1,2-a]indoles as novel high-affinity and selective imidazoline I2 receptor ligands

被引：10

作者：

Chang-Fong, J

Tyacke, RJ

Lau, A

Westaway, J

Hudson, AL

Glennon, RA

机构：

[1] Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA 23298 USA

[2] Univ Bristol, Sch Med Sci, Psychopharmacol Unit, Bristol BS8 1TD, Avon, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 04期

关键词：

D O I：

10.1016/j.bmcl.2003.12.033

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

1,2,3,4-Tetrahydropyrazino[1,2-a]indoles are described as a novel class of I-2 imidazoline receptor ligands. In particular, 8-methoxy-1,2,3,4-tetrahydropyrazino[1,2-a]indole (8-OMe THPI; 3c) binds with high affinity at I-2 imidazoline receptors (K-i = 6.2 nM) and with exceptional (greater than or equal to 1000-fold) selectivity relative to its affinity for I-1 imidazoline receptors, alpha(2)adrenergic receptors, and 5-HT2A and 5-HT2C serotonin receptors. (C) 2003 Elsevier Ltd. All rights reserved.

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页码：1003 / 1005

页数：3

相关论文

共 14 条

[1] Labelling of I-2B-imidazoline receptors by [H-3]2-(2-benzofuranyl)-2-imidazoline (2-BFI) in rat brain and liver: Characterization, regulation and relation to monoamine oxidase enzymes [J].

Alemany, R ;

Olmos, G ;

GarciaSevilla, JA .

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1997, 356 (01) :39-47

[2]

ANATASSIADOU M, 2001, BIOORGAN MED CHEM, V9, P585

[3] Attenuation of tolerance to opioid-induced antinociception by idazoxan and other I2-ligands [J].

Boronat, MA ;

Olmos, G ;

García-Sevilla, JA .

IMIDAZOLINE RECEPTORS AND THEIR ENDOGENOUS LIGANDS: CURRENT CONCEPTS AND THERAPEUTIC POTENTIAL, 1999, 881 :359-363

[4] Evaluation of isotryptamine derivatives at 5-HT2 serotonin receptors [J].

Chang-Fonga, J ;

Addo, J ;

Dukat, M ;

Smith, C ;

Mitchell, NA ;

Herrick-Davis, K ;

Teitler, M ;

Glennon, RA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (02) :155-158

[5]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[6] 'Seeing through a glass darkly': casting light on imidazoline 'I' sites [J].

Eglen, RM ;

Hudson, AL ;

Kendall, DA ;

Nutt, DJ ;

Morgan, NG ;

Wilson, VG ;

Dillon, MP .

TRENDS IN PHARMACOLOGICAL SCIENCES, 1998, 19 (09) :381-390

[7] Imidazoline binding sites (IBS) profile modulation:: Key role of the bridge in determining I1-IBS or I2-IBS selectivity within a series of 2-phenoxymethylimidazoline analogues [J].

Gentili, F ;

Bousquet, P ;

Brasili, L ;

Dontenwill, M ;

Feldman, J ;

Ghelfi, F ;

Giannella, M ;

Piergentili, A ;

Quaglia, W ;

Pigini, M .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (11) :2169-2176

[8] Binding of β-carbolines and related agents at serotonin (5-HT2 and 5-HT1A), dopamine (D2) and benzodiazepine receptors [J].

Glennon, RA ;

Dukat, M ;

Grella, B ;

Hong, SS ;

Costantino, L ;

Teitler, M ;

Smith, C ;

Egan, C ;

Davis, K ;

Mattson, MV .

DRUG AND ALCOHOL DEPENDENCE, 2000, 60 (02) :121-132

[9]

GLENNON RA, 2004, BIOORG MED CHEM LETT, V14

[10] Binding of β-carbolines at 5-HT2 serotonin receptors [J].

Grella, B ;

Teitler, M ;

Smith, C ;

Herrick-Davis, K ;

Glennon, RA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (24) :4421-4425