141071-80-9Relevant articles and documents
Synthesis, docking and pharmacological evaluation of novel homo- and hetero-bis 3-piperazinylpropylindole derivatives at SERT and 5-HT1A receptor
Pessoa-Mahana, Hernán,González-Lira, Christian,Fierro, Angélica,Zapata-Torres, Gerald,Pessoa-Mahana, C. David,Ortiz-Severin, Javiera,Iturriaga-Vásquez, Patricio,Reyes-Parada, Miguel,Silva-Matus, Paul,Saitz-Barría, Claudio,Araya-Maturana, Ramiro
, p. 7604 - 7611 (2013)
A series of 3-(3-(4-(3-(1H-indol-3-yl)propyl)piperazin-1-yl)propyl)-1H- indole derivatives (3a-d and 5a-f) as homo- and hetero-bis-ligands, were synthesized and evaluated for in vitro affinity at the serotonin transporter (SERT) and the 5-HT1A receptor. Compounds 5b and 5f showed nanomolar affinities for both targets. The experimental data were rationalized according to results obtained from docking experiments. These findings are in agreement with our proposal that bis-indole derivatives can bind both targets, and might serve as leads in the quest of ligands endowed with a dual mechanism of action.
Domino o-alkylation and heteroarylation of iodoarenes: One-pot synthesis of benzocyclohepta[b]indoles
Jafarpour, Farnaz,Otaredi-Kashani, Asieh,Behpajooh, Saeideh
, p. 1094 - 1098 (2013)
A new strategy for the synthesis of benzocyclohepta[b]indoles via a palladium-catalyzed/norbornene-mediated domino intermolecular alkylation/intramolecular heteroarylation of iodoarenes is devised. This approach provides a straightforward route to polycyclic nitrogen-containing heterocycles with fused seven-membered rings from readily accessible precursors. Georg Thieme Verlag Stuttgart New York.
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
, p. 235 - 248 (2020/02/18)
5-HT1A receptor (5-HT1AR) agonists have been implicated in the treatment of a variety of central nervous system (CNS) diseases such as depression and anxiety, et al. Based on our previously found compound FW01 (Ki = 51 ± 16 nM) obtained by virtual screening, a series of FW01 derivatives were designed and synthesized by the modification of the amide tail group as well as indole headgroup of FW01. SAR exploration found that amide tail group and indole headgroup play pivotal roles in determining the binding affinity and selectivity on dopamine and serotonin receptor subtypes. Among all tested compounds, 9_24 has a Ki value of 5 ± 0.6 nM with a good selectivity toward 5-HT1AR. The [35S] GTPγS assay showed that 9_24 is a full agonist toward 5-HT1AR with an EC50 value of 0.059 nM, which shows 266.2 and 146.4-fold selectivity to 5-HT2A and D3 respectively. Molecular dynamics simulations and molecular docking studies with 5-HT1AR-9_24 were performed to disclose the mechanism of its high activity and selectivity. Finally, a detailed stepwise 9_24 induced signal transduction mechanism of 5-HT1AR is proposed.
Synthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7
Gu, Zheng-Song,Wang, Wen-Tao,Qian, Hao,Zhou, Ai-Nan,Sun, Hong-Bin,Zhang, Qing-Wei,Li, Jian-Qi
supporting information, (2019/10/22)
A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a exhibited high affinities for the 5-HT1A/5-HT7 receptors (5-HT1A, Ki = 12 nM; 5-HT7, Ki = 3.2 nM) coupled with potent serotonin reuptake inhibition (IC50 = 14 nM) and showed a marked antidepressant-like effect in the FST and TST models.
