N-(substituted-phenyl) piperazines: Antagonists with high binding and functional selectivity for dopamine D-4 receptors

被引：17

作者：

Boyfield, I ^{[1
]}

Coldwell, MC ^{[1
]}

Hadley, MS ^{[1
]}

Healy, MAM ^{[1
]}

Johns, A ^{[1
]}

Nash, DJ ^{[1
]}

Riley, GJ ^{[1
]}

Scott, EE ^{[1
]}

Smith, SA ^{[1
]}

Stemp, G ^{[1
]}

Wilson, K ^{[1
]}

机构：

[1] SMITHKLINE BEECHAM PHARMACEUT,HARLOW CM19 5AW,ESSEX,ENGLAND

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1996年 / 6卷 / 11期

关键词：

D O I：

10.1016/0960-894X(96)00198-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-(substituted-phenyl) piperazine derivatives was prepared as selective antagonists of the dopamine D-4 receptor. Many analogues possessed a binding selectivity of over 100 fold for D-4 over D-2 receptors. In functional studies in the microphysiometer, compound 24 showed a selectivity over dopamine D-2 receptors of greater than 1000 fold. Copyright (C) 1996 Elsevier Science Ltd

引用

页码：1227 / 1232

页数：6

共 12 条

[1] CLONING OF THE CDNA AND GENE FOR A HUMAN D2-DOPAMINE RECEPTOR [J].

GRANDY, DK ;

MARCHIONNI, MA ;

MAKAM, H ;

STOFKO, RE ;

ALFANO, M ;

FROTHINGHAM, L ;

FISCHER, JB ;

BURKEHOWIE, KJ ;

BUNZOW, JR ;

SERVER, AC ;

CIVELLI, O .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (24) :9762-9766

[2] DRUG-TREATMENT OF SCHIZOPHRENIA - OVERVIEW OF RECENT RESEARCH [J].

MARDER, SR ;

WIRSHING, WC ;

VANPUTTEN, T .

SCHIZOPHRENIA RESEARCH, 1991, 4 (02) :81-90

[3] FULL-LENGTH CDNA CLONING AND DISTRIBUTION OF HUMAN DOPAMINE D4 RECEPTOR [J].

MATSUMOTO, M ;

HIDAKA, K ;

TADA, S ;

TASAKI, Y ;

YAMAGUCHI, T .

MOLECULAR BRAIN RESEARCH, 1995, 29 (01) :157-162

[4] EXPRESSION AND FUNCTIONAL-CHARACTERIZATION OF A SYNTHETIC VERSION OF THE HUMAN D-4 DOPAMINE-RECEPTOR IN A STABLE HUMAN CELL-LINE [J].

MCHALE, M ;

COLDWELL, MC ;

HERRITY, N ;

BOYFIELD, I ;

WINN, FM ;

BALL, S ;

COOK, T ;

ROBINSON, JH ;

GLOGER, IS .

FEBS LETTERS, 1994, 345 (2-3) :147-150

[5] DISTRIBUTION OF PUTATIVE D4 DOPAMINE-RECEPTORS IN POSTMORTEM STRIATUM FROM PATIENTS WITH SCHIZOPHRENIA [J].

MURRAY, AM ;

HYDE, TM ;

KNABLE, MB ;

HERMAN, MM ;

BIGELOW, LB ;

CARTER, JM ;

WEINBERGER, DR ;

KLEINMAN, JE .

JOURNAL OF NEUROSCIENCE, 1995, 15 (03) :2186-2191

[6]

REYNOLDS GP, 1994, J NEUROCHEM, V63, P1576

[7] DOPAMINE-RECEPTORS AND THE DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA [J].

SEEMAN, P .

SYNAPSE, 1987, 1 (02) :133-152

[8] DOPAMINE D4 RECEPTORS ELEVATED IN SCHIZOPHRENIA [J].

SEEMAN, P ;

GUAN, HC ;

VANTOL, HHM .

NATURE, 1993, 365 (6445) :441-445

[9] MOLECULAR-CLONING AND CHARACTERIZATION OF A NOVEL DOPAMINE RECEPTOR (D3) AS A TARGET FOR NEUROLEPTICS [J].

SOKOLOFF, P ;

GIROS, B ;

MARTRES, MP ;

BOUTHENET, ML ;

SCHWARTZ, JC .

NATURE, 1990, 347 (6289) :146-151

[10]

TALLMAN JF, 1994, AM COLL NEUR 33 ANN

← 1 2 →