Studies towards the identification of a new generation of atypical antipsychotic agents

被引：32

作者：

Garzya, Vincenzo

Forbes, Ian T.

Gribble, Andrew D.

Hadley, Mike S.

Lightfoot, Andrew P.

Payne, Andrew H.

Smith, Alexander B.

Douglas, Sara E.

Cooper, David G.

Stansfield, Ian G.

Meeson, Malcom

Dodds, Emma E.

Jones, Declan N. C.

Wood, Martyn

Reavill, Charlie

Scorer, Carol A.

Worby, Angela

Riley, Graham

Eddershaw, Peter

Ioannou, Chris

Donati, Daniele

Hagan, Jim J.

Ratti, Emiliangelo A.

机构：

[1] Psychiat Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England

[2] Discovery Res GlaxoSmithKline, Harlow CM19 5AW, Essex, England

[3] Med Res Ctr, I-37135 Verona, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 02期

关键词：

dopamine; serotonin; antagonist; sulfonamide; benzazepine; atypical; antipsychotic; schizophrenia;

D O I：

10.1016/j.bmcl.2006.10.036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A rational structure-activity relationship study around compound (1) is reported. The lead optimisation programme led to the identification of sulfonamide (25), a molecule combining dopamine D-2/D-3 receptor antagonism with serotonin 5-HT2A, 5-HT2C, 5-HT6 receptor antagonism for an effective treatment of schizophrenia. Compound (25) was shown to possess the required in vivo activity with no EPS liability. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：400 / 405

页数：6

共 25 条

[1]

BROMIDGE SM, 2003, Patent No. 2003068752

[2]

Bymaster FP, 1996, SCHIZOPHR RES, V18, pVIA2

[3] ANTIPSYCHOTIC-DRUGS, NEUROTRANSMITTERS, AND SCHIZOPHRENIA [J].