In pursuit of α4β2 nicotinic receptor partial agonists for smoking cessation:: Carbon analogs of (-)-cytisine

被引：55

作者：

Coe, JW ^{[1
]}

Vetelino, MG ^{[1
]}

Bashore, CG ^{[1
]}

Wirtz, MC ^{[1
]}

Brooks, PR ^{[1
]}

Arnold, EP ^{[1
]}

Lebel, LA ^{[1
]}

Fox, CB ^{[1
]}

Sands, SB ^{[1
]}

Davis, TI ^{[1
]}

Schulz, DW ^{[1
]}

Rollema, H ^{[1
]}

Tingley, FD ^{[1
]}

O'Neill, BT ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton Labs, Eastern Point Rd, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 12期

关键词：

alpha 4 beta 2 nicotinic receptor; nAChR; partial agonist; smoking; cessation; alkaloid;

D O I：

10.1016/j.bmcl.2005.04.036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The preparation and biological activity of analogs of (-)-cytisine, an alpha 4 beta 2 nicotinic receptor partial agonist, are discussed. All-carbon-containing phenyl ring replacements of the pyridone ring system, generated via Heck cyclization protocols, exhibited weaker affinity and lower efficacy partial agonist profiles relative to (-)-cytisine. In vivo, selected compounds exhibit lower efficacy partial agonist profiles than that of (-)-cytisine. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2974 / 2979

页数：6

共 62 条

[1] NICOTINIC RECEPTOR-BINDING OF [H-3] CYTISINE, [H-3] NICOTINE AND [H-3] METHYLCARBAMYLCHOLINE IN RAT-BRAIN [J].

ANDERSON, DJ ;

ARNERIC, SP .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1994, 253 (03) :261-267

[2]

[Anonymous], J CLIN PSYCHIAT MONO

[3] SOME STUDIES ON CYTISINE AND ITS METHYLATED DERIVATIVES [J].

BARLOW, RB ;

MCLEOD, LJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1969, 35 (01) :161-&

[4] Twisted amide reduction under Wolff-Kishner conditions: Synthesis of a benzo-1-aza-adamantane derivative [J].

Bashore, CG ;

Samardjiev, IJ ;

Bordner, J ;

Coe, JW .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (11) :3268-3272

[5]

BLACKHALL KY, 1995, J CHEM SOC P1, V21, P2767

[6]

Boido Caterina Canu, 2003, Farmaco (Lausanne), V58, P265, DOI 10.1016/S0014-827X(03)00017-X

[7] A short synthesis of (±)-cytisine [J].

Botuha, C ;

Galley, CMS ;

Gallagher, T .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2004, 2 (13) :1825-1826

[8] Synthesis of 2,3,4,5-tetrahydro-1,5-methano-1H-3-benzazepine via oxidative cleavage and reductive amination strategies [J].

Brooks, PR ;

Caron, S ;

Coe, JW ;

Ng, KK ;

Singer, RA ;

Vazquez, E ;

Vetelino, MG ;

Watson, HH ;

Whritenour, DC ;

Wirtz, MC .

SYNTHESIS-STUTTGART, 2004, (11) :1755-1758

[9] PREVENTING RELAPSE IN THE TREATMENT OF NICOTINE ADDICTION - CURRENT ISSUES AND FUTURE-DIRECTIONS [J].

CARMODY, TP .

JOURNAL OF PSYCHOACTIVE DRUGS, 1992, 24 (02) :131-158

[10]

CHANG WK, 1971, J MED CHEM, V14, P1011

← 1 2 3 4 5 6 7 →