Discovery of a new series of monoamine reuptake inhibitors, the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols

被引：13

作者：

Kim, Callain Y. ^{[1
]}

Mahaney, Paige E. ^{[1
]}

McConnell, Oliver ^{[1
]}

Zhang, Yingru ^{[1
]}

Manas, Eric ^{[1
]}

Ho, Douglas M. ^{[2
]}

Deecher, Darlene C. ^{[1
]}

Trybulski, Eugene J. ^{[1
]}

机构：

[1] Wyeth Res, Chem Sci, Collegeville, PA 19426 USA

[2] Princeton Univ, Dept Chem, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 17期

关键词：

Vasomotor symptoms; Monoamine reuptake inhibitor; Norepiephrine reuptake inhibitor; NRI; NE; 5-HT; ENANTIOMERIC SEPARATION; CHIRAL TECHNOLOGY; NOREPINEPHRINE; ANTIDEPRESSANT; REBOXETINE; EFFICACY;

D O I：

10.1016/j.bmcl.2009.07.053

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of monoamine reuptake inhibitors, the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols, have been discovered by combining virtual and focused screening efforts with design techniques. Synthesis of the two diastereomeric isomers of the molecule followed by chiral resolution of each enantiomer revealed the (2R,3S)-isomer to be a potent norepinephrine reuptake inhibitor (IC50 = 28 nM) with excellent selectivity over the dopamine transporter and 13-fold selectivity over the serotonin transporter. (C) 2009 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5029 / 5032

页数：4

相关论文

共 50 条

[41] 8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: Dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors-Part II [J].

Bromidge, Steven M. ;

Bertani, Barbara ;

Borriello, Manuela ;

Bozzoli, Andrea ;

Faedo, Stefania ;

Gianotti, Massimo ;

Gordon, Laurie J. ;

Hill, Matthew ;

Zucchelli, Valeria ;

Watson, Jeannette M. ;

Zonzini, Laura .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (08) :2338-2342

[42] Microwave-assisted synthesis of 2-(4,5-dihydro-5-(tetrazolo[1,5-a]quinoline-4-yl)-1H-pyrazol-3-yl)-substituted phenols [J].

Ashok, Dongamanti ;

Rao, Velagapuri Hanumantha ;

Sreenivas, Peddolla .

HETEROCYCLIC COMMUNICATIONS, 2013, 19 (05) :363-367

[43] Discovery of (E)-N1-(3-Fluorophenyl)-N3-(3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)malonamide (CHMFL-KIT-033) as a Novel c-KIT T670I Mutant Selective Kinase Inhibitor for Gastrointestinal Stromal Tumors (GISTs) [J].

Liu, Xuesong ;

Wang, Beilei ;

Chen, Cheng ;

Qi, Ziping ;

Zou, Fengming ;

Wang, Junjie ;

Hu, Chen ;

Wang, Aoli ;

Ge, Juan ;

Liu, Qingwang ;

Yu, Kailin ;

Hu, Zhenquan ;

Jiang, Zongru ;

Wang, Wei ;

Wang, Li ;

Wang, Wenchao ;

Ren, Tao ;

Bai, Mingfeng ;

Liu, Qingsong ;

Liu, Jing .

JOURNAL OF MEDICINAL CHEMISTRY, 2019, 62 (10) :5006-5024

[44] Crystal structure of 3-(adamantan-1-yl)-4-(4fluorophenyl)-1H-1,2,4-triazole-5(4H)-thione,C18H20FN3S [J].

Al-Shehri, Mona M. ;

Elsaman, Tilal ;

Al-Abdullah, Ebtehal S. ;

Ghabbour, Hazem A. ;

El-Emam, Ali A. .

ZEITSCHRIFT FUR KRISTALLOGRAPHIE-NEW CRYSTAL STRUCTURES, 2017, 232 (03) :443-445

[45] The novel compound (±)-1-[10-((E)-3-Phenyl-allyl)-3,10-diazabicyclo[4.3.1]dec-3-yl]-propan-1-one (NS7051) attenuates nociceptive transmission in animal models of experimental pain;: a pharmacological comparison with the combined μ-opioid receptor agonist and monoamine reuptake inhibitor tramadol [J].

Munro, Gordon ;

Baek, Camilla AE. ;

Erichsen, Helle K. ;

Nielsen, Alexander N. ;

Nielsen, Elsebet O. ;

Scheel-Kruger, Jorgen ;

Weikop, Pia ;

Peters, Dan .

NEUROPHARMACOLOGY, 2008, 54 (02) :331-343

[46] Discovery of Novel 1,2,3,4-Tetrahydrobenzofuro[2,3-c]pyridine Histone Deacetylase Inhibitors for Efficient Treatment of Hepatocellular Carcinoma [J].

Lai, Zhencheng ;

Ni, Hao ;

Hu, Xueping ;

Cui, Sunliang .

JOURNAL OF MEDICINAL CHEMISTRY, 2023, 66 (15) :10791-10807

[47] N-[2-[(3-Chlorophenyl)amino]-phenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide: Synthesis, Crystal Structure, Molecular Docking and Biological Activities [J].

Zhang, Aigui ;

Yang, Yihua ;

Yue, Ying ;

Tao, Ke ;

Hou, Taiping ;

Jin, Hong .

CHEMISTRY & BIODIVERSITY, 2019, 16 (07)

[48] Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts [J].

Marvanova, Pavlina ;

Padrtova, Tereza ;

Pekarek, Tomas ;

Brus, Jiri ;

Czernek, Jiri ;

Mokry, Petr ;

Humpa, Otakar ;

Oravec, Michal ;

Jampilek, Josef .

MOLECULES, 2016, 21 (06)

[49] Discovery, Structure-Activity Relationship, and Mechanistic Studies of 1-((3R,4S)-3-((Dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)piperidin-1-yl)-2-(2,4,5-trifluorophenyl)ethan-1-one as a Novel Potent Analgesic [J].

Huang, Huoming ;

Li, Xueping ;

Xie, Peng ;

Li, Xinwei ;

Xu, XueJun ;

Qian, Yuanyuan ;

Yuan, Congmin ;

Meng, Xiangguo ;

Chai, JingRui ;

Chen, Jing ;

Liu, Jing ;

Wang, Wenli ;

Li, Wei ;

Wang, YuJun ;

Fu, Wei ;

Liu, Jinggen .

JOURNAL OF MEDICINAL CHEMISTRY, 2021, 64 (13) :9458-9483

[50] N-(3-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl} propyl)-1H-indazole-3-carboxamide (D2AAK3) as a potential antipsychotic: In vitro, in silico and in vivo evaluation of a multi-target ligand [J].

Kaczor, Agnieszka A. ;

Targowska-Duda, Katarzyna M. ;

Stepnicki, Piotr ;

Silva, Andrea G. ;

Koszla, Oliwia ;

Kedzierska, Ewa ;

Grudzinska, Angelika ;

Kruk-Slomka, Marta ;

Biala, Grazyna ;

Castro, Marian .

NEUROCHEMISTRY INTERNATIONAL, 2021, 146

← 1 2 3 4 5 →