Design, synthesis, and pharmacological evaluation of azetedine and pyrrolidine derivatives as dual norepinephrine reuptake inhibitors and 5-HT1A partial agonists

被引：14

作者：

Pettersson, Martin ^{[1
]}

Campbell, Brian M. ^{[1
]}

Dounay, Amy B. ^{[1
]}

Gray, David L. ^{[1
]}

Xie, Longfei ^{[1
]}

O'Donnell, Christopher J. ^{[1
]}

Stratman, Nancy C. ^{[1
]}

Zoski, Kim ^{[1
]}

Drummond, Elena ^{[1
]}

Bora, Gary ^{[1
]}

Probert, Al ^{[1
]}

Whisman, Tammy ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 02期

关键词：

Norepinephrine reuptake inhibitor; 5-HT1A agonist; NRI; NET; DAT; SERT; ADHD; Depression; EFFICACY; REBOXETINE;

D O I：

10.1016/j.bmcl.2010.11.066

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compounds with combined norepinephrine reuptake inhibitor (NRI) and serotonin 1A (5-HT1A) partial agonist pharmacology may offer a new therapeutic approach for treating symptoms of neuropsychiatric disorders including ADHD, depression, and anxiety. Herein we describe the design and optimization of novel chemical matter that exhibits favorable dual NRI and 5-HT1A partial agonist activity. Lead compounds in this series were found to be devoid of activity at the dopamine transporter and were shown to be brain penetrant with high receptor occupancy. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：865 / 868

页数：4

共 50 条

[31] ATTENUATION OF OPIOID INDUCED ANTINOCICEPTION BY 5-HT1A PARTIAL AGONISTS IN THE RAT
MILLAN, MJ
COLPAERT, FC
NEUROPHARMACOLOGY, 1990, 29 (03) : 315 - 318
[32] Rigid analogues of buspirone and gepirone, 5-HT1A receptors partial agonists
Chilmonczyk, Z
Krajewski, KJ
Cybulski, J
FARMACO, 2002, 57 (11): : 917 - 923
[33] 5-HT1A autoreceptors and the mode of action of selective serotonin reuptake inhibitors (SSRI)
Hjorth, S
Auerbach, SB
BEHAVIOURAL BRAIN RESEARCH, 1996, 73 (1-2) : 281 - 283
[34] Design, Synthesis, and Structure-Activity Relationship Studies of Novel Indolyalkylpiperazine Derivatives as Selective 5-HT1A Receptor Agonists
Wang, Wenli
Zheng, Lan
Li, Wei
Zhu, Chen
Peng, Weiqing
Han, Bing
Fu, Wei
JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2020, 60 (01) : 235 - 248
[35] Synthesis and pharmacological evaluation of carboxamide derivatives as selective serotoninergic 5-HT4 receptor agonists
Itoh, K
Kanzaki, K
Ikebe, T
Kuroita, T
Tomozane, H
Sonda, S
Sato, N
Haga, K
Kawakita, T
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1999, 34 (04) : 329 - 341
[36] Synthesis and pharmacological evaluation of carboxamide derivatives as selective serotoninergic 5-HT4 receptor agonists
Itoh, K
Kanzaki, K
Ikebe, T
Kuroita, T
Tomozane, H
Sonda, S
Sato, N
Haga, K
Kawakita, T
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1999, 34 (11) : 977 - 989
[37] Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of Rat Prefrontal Cortical Dopamine Response to Dual Acting Norepinephrine Reuptake Inhibitor and 5-HT1A Partial Agonist
Li, Cheryl Shuang-wu
Zhang, Liming
Haske, Taraneh
Dounay, Amy
Gray, David
Barta, Nancy
Brodfuehrer, Joanne
Lepsy, Christopher
Campbell, Brian
AAPS JOURNAL, 2012, 14 (02): : 365 - 376
[38] Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of Rat Prefrontal Cortical Dopamine Response to Dual Acting Norepinephrine Reuptake Inhibitor and 5-HT1A Partial Agonist
Cheryl Shuang-wu Li
Liming Zhang
Taraneh Haske
Amy Dounay
David Gray
Nancy Barta
Joanne Brodfuehrer
Christopher Lepsy
Brian Campbell
The AAPS Journal, 2012, 14 : 365 - 376
[39] SYNTHESIS OF METABOLICALLY STABLE ARYLPIPERAZINE 5-HT1A RECEPTOR AGONISTS
ROMERO, AG
DARLINGTON, WH
PIERCEY, MF
LAHTI, RA
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1992, 2 (12) : 1703 - 1706
[40] Novel. selective and potent 5-HT reuptake inhibitors with 5-HT1D antagonist activity:: chemistry and pharmacological evaluation of a series of thienopyran derivatives
Torrado, A
Lamas, C
Agejas, J
Jiménez, A
Díaz, N
Gilmore, J
Boot, J
Findlay, J
Hayhurst, L
Wallace, L
Broadmore, R
Tomlinson, R
BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (20) : 5277 - 5295

← 1 2 3 4 5 →