Synthesis of new 4-butyl-arylpiperazine-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives and evaluation for their 5-HT1A and D2 receptor affinity and serotonin transporter inhibition

被引：15

作者：

Wrobel, Martyna Z. ^{[1
]}

Chodkowski, Andrzej ^{[1
]}

Marciniak, Monika ^{[1
]}

Dawidowski, Maciej ^{[1
]}

Maksymiuk, Anna ^{[1
]}

Siwek, Agata ^{[2
]}

Nowak, Gabriel ^{[2
,3
]}

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

来源：

BIOORGANIC CHEMISTRY | 2020年 / 97卷

关键词：

Long-chain arylpiperazines; Depression; 5-HT1A receptor ligands; Schizophrenia; Multi-target ligands; DOPAMINE D-3; CNS AGENTS; ANTIDEPRESSANT; LIGANDS; ANALOGS; BINDING; PATHOPHYSIOLOGY; DEPRESSION; VILAZODONE; DISCOVERY;

D O I：

10.1016/j.bioorg.2020.103662

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of novel 4-butyl-arylpiperazine-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives were synthesized and evaluated for their 5-HT1A/D-2 receptor affinity and serotonin reuptake inhibition. The compounds exhibited high affinity for the 5-HT1A receptor, (especially 4d K-i = 0.4 nM) which depended on the substitution pattern at the phenylpiperazine moiety. From this series screen, compound 4c emerged with promising mixed receptor profiles for the 5-HT1A/D-2 receptors and the serotonin transporter (K-i = 1.3 nM, 182 nM and 64 nM, respectively).

引用

页数：9

共 48 条

[1] Synthesis and SAR of adatanserin:: Novel adamantyl aryl- and heteroarylpiperazines with dual serotonin 5-HT1A and 5-HT2 activity as potential anxiolytic and antidepressant agents [J].