Dual serotonin transporter/histamine H3 ligands:: Optimization of the H3 pharmacophore

被引：35

作者：

Keith, John M. ^{[1
]}

Gomez, Leslie A. ^{[1
]}

Letavic, Michael A. ^{[1
]}

Ly, Kiev S. ^{[1
]}

Jablonowski, Jill A. ^{[1
]}

Seierstad, Mark ^{[1
]}

Barbier, Ann J. ^{[1
]}

Wilson, Sandy J. ^{[1
]}

Boggs, Jamin D. ^{[1
]}

Fraser, Ian C. ^{[1
]}

Mazur, Curt ^{[1
]}

Lovenberg, Timothy W. ^{[1
]}

Carruthers, Nicholas I. ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 03期

关键词：

serotonin transporter; histamine H-3; ring-closure; 5-HTP potentiation;

D O I：

10.1016/j.bmcl.2006.10.089

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of tetrahydroisoquinolines acting as dual histamine H-3/serotonin transporter ligands is described. A highly regioselective synthesis of the tetrahydroisoquinoline core involving acid mediated ring-closure of an acetophenone intermediate followed by reduction with NaCNBH3 was developed. In vitro and in vivo data are discussed. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：702 / 706

页数：5

共 18 条

[1] A new class of diamine-based human histamine H3 receptor antagonists:: 4-(aminoalkoxy)benzylamines [J].

Apodaca, R ;

Dvorak, CA ;

Xiao, W ;

Barbier, AJ ;

Boggs, JD ;

Wilson, SJ ;

Lovenberg, TW ;

Carruthers, NI .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (18) :3938-3944

[2] Acute wake-promoting actions of JNJ-5207852, a novel, diamine-based H3 antagonist [J].

Barbier, AJ ;

Berridge, C ;

Dugovic, C ;

Laposky, AD ;

Wilson, SJ ;

Boggs, J ;

Aluisio, L ;

Lord, B ;

Mazur, C ;

Pudiak, CM ;

Langlois, X ;

Xiao, W ;

Apodaca, R ;

Carruthers, NI ;

Lovenberg, TW .

BRITISH JOURNAL OF PHARMACOLOGY, 2004, 143 (05) :649-661

[3] Adverse events and treatment discontinuations in clinical trials of fluoxetine in major depressive disorder: An updated meta-analysis [J].

Beasley, CM ;

Koke, SC ;

Nilsson, ME ;

Gonzales, JS .

CLINICAL THERAPEUTICS, 2000, 22 (11) :1319-+

[4]

CARRUTHERS NI, 2006, Patent No. 206066197

[5] Non-imidazole heterocyclic histamine H3 receptor antagonists [J].

Chai, WY ;

Breitenbucher, JG ;

Kwok, A ;

Li, XB ;

Wong, V ;

Carruthers, NI ;

Lovenberg, TW ;

Mazur, C ;

Wilson, SJ ;

Axe, FU ;

Jones, TK .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (10) :1767-1770

[6]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[7] The stimulatory and inhibitory components of cocaine's actions on the 5-HTP-induced 5-HT2A receptor response [J].

Darmani, NA ;

Reeves, SL .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1996, 55 (03) :387-396

[8] 4-Phenoxypiperidines:: Potent, conformationally restricted, non-imidazole histamine H3 antagonists [J].

Dvorak, CA ;

Apodaca, R ;

Barbier, AJ ;

Berridge, CW ;

Wilson, SJ ;

Boggs, JD ;

Xiao, W ;

Lovenberg, TW ;

Carruthers, NI .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (06) :2229-2238

[9] Residual symptoms in depression: An emerging therapeutic target [J].

Fava, GA ;

Fabbri, S ;

Sonino, N .

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2002, 26 (06) :1019-1027

[10] Predictors of efficacy in depression prevention programmes -: Meta-analysis [J].

Jané-Llopis, E ;

Hosman, C ;

Jenkins, R ;

Anderson, P .

BRITISH JOURNAL OF PSYCHIATRY, 2003, 183 :384-397

← 1 2 →