Synthesis and biological evaluation of new multi-target 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with potential antidepressant effect

被引：25

作者：

Wrobel, Martyna Z. ^{[1
]}

Chodkowski, Andrzej ^{[1
]}

Herold, Franciszek ^{[1
]}

Marciniak, Monika ^{[1
]}

Dawidowski, Maciej ^{[1
]}

Siwek, Agata ^{[2
]}

Starowicz, Gabriela ^{[2
]}

Stachowicz, Katarzyna ^{[3
]}

Szewczyk, Bernadeta ^{[3
]}

Nowak, Gabriel ^{[2
,3
]}

Belka, Mariusz ^{[4
]}

Baczek, Tomasz ^{[4
]}

Satala, Grzegorz ^{[5
]}

Bojarski, Andrzej J. ^{[5
]}

Turlo, Jadwiga ^{[1
]}

机构：

[1] Med Univ Warsaw, Fac Pharm, Dept Drug Technol & Pharmaceut Biotechnol, 1 Banacha St, PL-02097 Warsaw, Poland

[2] Jagiellonian Univ, Fac Pharm, Dept Pharmacobiol, Med Coll, 9 Med St, PL-30688 Krakow, Poland

[3] Polish Acad Sci, Maj Inst Pharmacol, Dept Neurobiol, 12 Smetna St, PL-31343 Krakow, Poland

[4] Med Univ Gdansk, Dept Pharmaceut Chem, PL-80416 Gdansk, Poland

[5] Polish Acad Sci, Maj Inst Pharmacol, Dept Med Chem, 12 Smetna St, PL-31343 Krakow, Poland

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2019年 / 183卷

关键词：

Multitarget directed ligand; 5-HT1A agonists; 5-HT1A/SERT dual activity; Serotonin reuptake inhibitors; D-2 receptor ligands; Antidepressants; 5-HT1A RECEPTOR LIGANDS; DOPAMINE; SEROTONIN; METABOLISM; AGONISTS; SYSTEM; NEUROTRANSMISSION; PATHOPHYSIOLOGY; BREXPIPRAZOLE; SCHIZOPHRENIA;

D O I：

10.1016/j.ejmech.2019.111736

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives were synthesised and evaluated for their 5-HT1A/D-2/5-HT2A/5-HT6/5-HT7 receptor affinity and serotonin reuptake inhibition. Most of the evaluated compounds displayed high affinities for 5-HT1A receptors (e.g., 4c K-i = 23 nM, 41 K-i = 3.2 nM). The antidepressant activity of the selected compounds was screened in vivo using the forced swim test (FST). The results indicate that compound MWOOS (agonist of the pre- and postsynaptic 5-HT1A receptor) exhibited promising affinities for the 5-HT1A/SERT/D-2/5-HT6/5-HT7 receptors and showed an antidepressant-like activity in the FST model. (C) 2019 Elsevier Masson SAS. All rights reserved.

引用

页数：18

共 50 条

[21] Discovery of New 3-(Benzo[b]Thiophen-2-yl)Pyrrolidine-2,5-Dione Derivatives as Potent Antiseizure and Antinociceptive Agents-In Vitro and In Vivo Evaluation
Rapacz, Anna
Jakubiec, Marcin
Abram, Michal
Jasinski, Jakub
Chrzan, Karolina
Gora, Malgorzata
Dziubina, Anna
Wojcik-Pszczola, Katarzyna
Koczurkiewicz-Adamczyk, Paulina
Ciepiela, Katarzyna
Pekala, Elzbieta
Obniska, Jolanta
Kaminski, Krzysztof
PHARMACEUTICALS, 2024, 17 (11)
[22] Antinociceptive and Antiallodynic Activity of Some 3-(3-Methylthiophen-2-yl)pyrrolidine-2,5-dione Derivatives in Mouse Models of Tonic and Neuropathic Pain
Dziubina, Anna
Rapacz, Anna
Czopek, Anna
Gora, Malgorzata
Obniska, Jolanta
Kaminski, Krzysztof
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (07)
[23] 1-(2-Hydroxyethyl)-3-[(2-hydroxyethyl)amino]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione
Xie, Zhi-Xiong
Zhao, Sheng-Yin
ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, 2011, 67 : O854 - U329
[24] SYNTHESIS OF 3-OCTYL-3-(PROP-2-YNYL)PYRROLIDINE-2,5-DIONE, 3-CYCLOHEXYLMETHYL-3-(PROP-2-YNYL)PYRROLIDINE-2,5-DIONE AND 3-CARBOXY-3-(PROP-2-YNYL)PYRROLIDINE-2,5-DIONES REQUIRED AS POTENTIAL AROMATASE INHIBITORS
WOO, LWL
SMITH, HJ
BARRELL, KJ
NICHOLLS, PJ
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1993, (21): : 2549 - 2553
[25] Synthesis and evaluation of 1-(1H-indol-3-yl)ethanamine derivatives as new antibacterial agents
Burchak, Olga N.
Le Pihive, Emmanuelle
Maigre, Laure
Guinchard, Xavier
Bouhours, Pascale
Jolivalt, Claude
Schneider, Dominique
Maurin, Max
Giglione, Carmela
Meinnel, Thierry
Paris, Jean-Marc
Denis, Jean-Noel
BIOORGANIC & MEDICINAL CHEMISTRY, 2011, 19 (10) : 3204 - 3215
[26] Evaluation of anticonvulsant and antinociceptive properties of new N-Mannich bases derived from pyrrolidine-2,5-dione and 3-methylpyrrolidine-2,5-dione
Rapacz, Anna
Rybka, Sabina
Obniska, Jolanta
Saat, Kinga
Powroznik, Beata
Pekala, Elzbieta
Filipek, Barbara
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2016, 389 (03) : 339 - 348
[27] Evaluation of anticonvulsant and antinociceptive properties of new N-Mannich bases derived from pyrrolidine-2,5-dione and 3-methylpyrrolidine-2,5-dione
Anna Rapacz
Sabina Rybka
Jolanta Obniska
Kinga Sałat
Beata Powroźnik
Elżbieta Pękala
Barbara Filipek
Naunyn-Schmiedeberg's Archives of Pharmacology, 2016, 389 : 339 - 348
[28] Synthesis and Antidepressant Activity of Some New 5-(1H-Indol-3-yl)-3-(substituted aryl)-4,5-dihydroisoxazoline Derivatives
Patil, Pravin O.
Bari, Sanjay B.
JOURNAL OF CHEMISTRY, 2013, 2013
[29] Synthesis, characterization, and SAR studies of new (1H-indol-3-yl)alkyl-3-(1H-indol-3-yl)propanamide derivatives as possible antimicrobial and antitubercular agents
Ranjith Pakkath Karuvalam
Rajeesh Pakkath
Karickal Raman Haridas
Rathnasamy Rishikesan
Nalilu Suchetha Kumari
Medicinal Chemistry Research, 2013, 22 : 4437 - 4454
[30] 3,4-Bis[1-(prop-2-ynyl)-1H-indol-3-yl]1H- pyrrole-2,5-dione
Huang, Mu-Hua
Gao, Yong-Chen
Yang, Feng-Ling
Luo, Yun-Jun
ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, 2013, 69 : O924 - +

← 1 2 3 4 5 →