Clozapine derived 2,3-dihydro-1H-1,4-and 1,5-benzodiazepines with D4 receptor selectivity:: synthesis and biological testing

被引：37

作者：

Hussenether, T ^{[1
]}

Hübner, H ^{[1
]}

Gmeiner, P ^{[1
]}

Troschütz, R ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Emil Fischer Ctr, Dept Med Chem, D-91052 Erlangen, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 10期

关键词：

D O I：

10.1016/j.bmc.2004.03.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Novel 4-arylpiperazin-l-yl-substituted 2,3-dihydro-1H-1,4- and 1H-1,5-benzodiazepines and their aza-analogues were synthesized as debenzoclozapine derivatives for evaluation as potential D4-ligands. While K-i values of some of the title compounds came within the range of clozapine, they showed an impressively greater selectivity over other dopamine receptor subtypes, especially D2. For the most promising compounds, intrinsic activity and binding properties to serotonin 5-HT1(A) and 5-HT2 were also determined. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：2625 / 2637

页数：13

共 41 条

[1] MODULATION OF INTRACELLULAR CYCLIC-AMP LEVELS BY DIFFERENT HUMAN DOPAMINE D4 RECEPTOR VARIANTS [J].

ASGHARI, V ;

SANYAL, S ;

BUCHWALDT, S ;

PATERSON, A ;

JOVANOVIC, V ;

VANTOL, HHM .

JOURNAL OF NEUROCHEMISTRY, 1995, 65 (03) :1157-1165

[2] MONOMERS AND POLYMERS .6. THE PREPARATION OF VINYL DERIVATIVES OF 5-ATOM HETEROCYCLIC RINGS [J].

BACHMAN, GB ;

HEISEY, LV .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1949, 71 (06) :1985-1988

[3]

BAUER A, 1972, ARCH PHARM (WEINHEIM W GER), V305, P557, DOI 10.1002/ardp.19723050802

[4] SOME REACTIONS OF SUBSTITUTED 2-BROMOPYRIDINES [J].

BERRIE, AH ;

NEWBOLD, GT ;

SPRING, FS .

JOURNAL OF THE CHEMICAL SOCIETY, 1952, (JUN) :2042-2046

[5] HETEROARENOBENZODIAZEPINES .3. 4-PIPERAZINYL-10H-THIENO[2,3-B][1,5]BENZODIAZEPINES AS POTENTIAL NEUROLEPTICS [J].

CHAKRABARTI, JK ;

HORSMAN, L ;

HOTTEN, TM ;

PULLAR, IA ;

TUPPER, DE ;

WRIGHT, FC .

JOURNAL OF MEDICINAL CHEMISTRY, 1980, 23 (08) :878-884

[6]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[7] SYNTHESIS OF 5-AMINO-2,3-DIHYDRO-1H-1,4-BENZODIAZEPINES [J].

CORRAL, C ;

MADRONERO, R ;

VEGA, S .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1977, 14 (06) :985-988

[8]

DAVIS KL, 1991, AM J PSYCHIAT, V148, P1474

[9] Discovery and structure-activity relationships of imidazole-containing tetrahydrobenzodiazepine inhibitors of farnesyltransferase [J].

Ding, CZ ;

Batorsky, R ;

Bhide, R ;

Chao, HGJ ;

Cho, Y ;

Chong, S ;

Gullo-Brown, J ;

Guo, P ;

Kim, SH ;

Lee, F ;

Leftheris, K ;

Miller, A ;

Mitt, T ;

Patel, M ;

Penhallow, BA ;

Ricca, C ;

Rose, WC ;

Schmidt, R ;

Slusarchyk, WA ;

Vite, G ;

Yan, N ;

Manne, V ;

Hunt, JT .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (25) :5241-5253

[10] Synthesis of new benzo-substituted macrocyclic ligands containing pyridine or triazole as subcyclic units [J].

Elwahy, AHM ;

Abbas, AA .

TETRAHEDRON, 2000, 56 (06) :885-895

← 1 2 3 4 5 →