Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia

被引：20

作者：

Yan, Yinfa ^{[1
]}

Zhou, Ping ^{[1
]}

Rotella, David P. ^{[1
]}

Feenstra, Rolf ^{[2
]}

Kruse, Chris G. ^{[2
]}

Reinders, Jan-Hendrik ^{[2
]}

van der Neut, Martina ^{[2
]}

Lai, Margaret ^{[3
]}

Zhang, Jean ^{[3
]}

Kowal, Dianne M. ^{[3
]}

Carrick, Tikva ^{[3
]}

Marquis, Karen L. ^{[3
]}

Pausch, Mark H. ^{[3
]}

Robichaud, Albert J. ^{[1
]}

机构：

[1] Wyeth Res, Chem Sci, Princeton, NJ 08543 USA

[2] Solvay Pharmaceut Res Labs, NL-1381 CP Weesp, Netherlands

[3] Wyeth Res, Discovery Neurosci, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 09期

关键词：

Serotonin reuptake inhibitor; Dopamine D-2 partial agonist; Schizophrenia; DEPRESSION; ARIPIPRAZOLE; COMBINATION; OLANZAPINE; FLUOXETINE;

D O I：

10.1016/j.bmcl.2010.02.105

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D-2 ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D-2 partial agonists and serotonin reuptake inhibitors. Structure-activity studies revealed that the linker plays a key role in contributing to D-2 affinity, function, and SRI activity. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2983 / 2986

页数：4

共 12 条

[1] Comparison of fluoxetine, olanzapine, and combined fluoxetine plus olanzapine initial therapy of bipolar type I and type II major depression - lack of manic induction
Amsterdam, JD
Shults, J
[J]. JOURNAL OF AFFECTIVE DISORDERS, 2005, 87 (01) : 121 - 130
[2] Olanzapine/Fluoxetine Combination for the Treatment of Mixed Depression in Bipolar I Disorder: A Post Hoc Analysis
Benazzi, Franco
Berk, Michael
Frye, Mark A.
Wang, Wei
Barraco, Alessandra
Tohen, Mauricio
[J]. JOURNAL OF CLINICAL PSYCHIATRY, 2009, 70 (10) : 1424 - 1431
[3] CHRIS LB, 2002, CURR CONTR TRIALS C, V3, P7
[4] FAILLI AA, 2008, Patent No. 20070530
[5] GALANTE RJ, 2007, Patent No. 2007139998
[6] GARY PS, 1999, Patent No. 5869490
[7] Aripiprazole
McGavin, JK
Goa, KL
[J]. CNS DRUGS, 2002, 16 (11) : 779 - 786
[8] MELZER HY, 1999, NEUROPSYCHOPHARMACOL, V21, pS106
[9] New generation dopaminergic agents.: 2.: Discovery of 3-OH-phenoxyethnamine and 3-OH-N1-phenylpiperazine dopaminergic templates
Mewshaw, RE
Husbands, M
Gildersleeve, ES
Webb, MB
Shi, XJ
Mazandarani, H
Cockett, MI
Ochalski, R
Brennan, JA
Abou-Gharbia, M
Marquis, K
McGaughey, GB
Coupet, J
Andree, TH
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (03) : 295 - 300
[10] Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia
Rotella, David P.
McFarlane, Geraldine R.
Greenfield, Alexander
Grosanu, Cristina
Robichaud, Albert J.
Denny, Rajiah Aldrin
Feenstra, Rolf W.
Nunez-Garcia, Sara
Reinders, Jan-Hendrik
van der Neut, Martina
McCreary, Andrew
Kruse, Chris G.
Sullivan, Kelly
Pruthi, Farhana
Lai, Margaret
Zhang, Jean
Kowal, Dianne M.
Carrick, Tikva
Grauer, Steven M.
Navarra, Rachel L.
Graf, Radka
Brennan, Julie
Marquis, Karen L.
Pausch, Mark H.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (19) : 5552 - 5555

← 1 2 →