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.
A direct and simple approach for the synthesis of indole-3-propanol and its acetates from dihydropyran
Srinivasa, Aswathanarayana,Mahadevan, Kittappa M.,Sureshakumara, Tholappanavara H.,Hulikal, Vijaykumar
, p. 1475 - 1478 (2008)
A general method was developed for the one-pot synthesis of highly functionalized indoles from simple, commercially available phenylhydrazine hydrochlorides and dihydropyran. Synthesis of indole-3-propanol and its acetates was studied extensively for appropriate acetic acid and water mixture as the solvent.
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.
Synthesis of CF3-Containing Spirocyclic Indolines via a Red-Light-Mediated Trifluoromethylation/Dearomatization Cascade
Gianetti, Thomas L.,Mei, Liangyong,Moutet, Jules,Stull, Savannah M.
supporting information, p. 10640 - 10653 (2021/07/31)
A red-light-mediated nPr-DMQA+-catalyzed cascade intramolecular trifluoromethylation and dearomatization of indole derivatives with Umemoto's reagent has been developed. This protocol provides a facile and efficient approach for the construction of functionalized and potentially biologically important CF3-containing 3,3-spirocyclic indolines with moderate to high yields and excellent diastereoselectivities under mild conditions. The success of multiple gram-scale (1 and 10 g) experiments further highlights the robustness and practicality of this protocol and the merit of the employment of red light. Mechanistic studies support the formation of a crucial CF3 radical species and a dearomatized benzyl carbocation intermediate.
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.
Indole derivatives and its application on the medicament
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Paragraph 0383-0386; 0412; 0414-0417, (2019/03/28)
The invention provides indole derivatives or stereisomers, tautomers, nitrogen oxides, solvate, metabolic products, pharmaceutically acceptable salts or prodrugs thereof for treating the alzheimer disease. The invention further discloses a pharmaceutical composition containing the compounds and a method of using the compounds or the pharmaceutical composition thereof to treat the alzheimer disease.
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.
Synthesis and antidepressant-like activity of novel aralkyl piperazine derivatives targeting SSRI/5-HT1A/5-HT7
Gu, Zheng-Song,Zhou, Ai-nan,Xiao, Ying,Zhang, Qing-Wei,Li, Jian-Qi
, p. 701 - 715 (2018/01/03)
A series of novel aralkyl piperazine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the compounds were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compounds 21k (RUI, IC50 = 31 nM; 5-HT1A, 5-HT7, ki = 62, 12 nM) and 21n (RUI, IC50 = 25 nM; 5-HT1A, 5-HT7, ki = 28, 3.3 nM) exhibited high affinities for the 5-HT1A/5-HT7 receptors coupled with potent serotonin reuptake inhibition. Specifically, the most promising compound 21n possessed a good oral pharmacokinetic properties and an acceptable hERG profile, and showed potent antidepressant-like effect in the FST and TST models.
Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core
Méndez-Rojas, Claudio,Quiroz, Gabriel,Faúndez, Mario,Gallardo-Garrido, Carlos,Pessoa-Mahana, C. David,Chung, Hery,Gallardo-Toledo, Eduardo,Saitz-Barría, Claudio,Araya-Maturana, Ramiro,Kogan, Marcelo J.,Zú?iga-López, María C.,Iturriaga-Vásquez, Patricio,Valenzuela-Gutiérrez, Carla,Pessoa-Mahana, Hernán
, (2018/04/06)
With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 μM and 20.2 ± 0.9 μM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.
Palladium-Catalyzed Asymmetric Allylic Alkylation of 3-Substituted 1 H-Indoles and Tryptophan Derivatives with Vinylcyclopropanes
Trost, Barry M.,Bai, Wen-Ju,Hohn, Christoph,Bai, Yu,Cregg, James J.
supporting information, p. 6710 - 6717 (2018/05/24)
Vinylcyclopropanes (VCPs) are known to generate 1,3-dipoles with a palladium catalyst that initially serve as nucleophiles to undergo [3 + 2] cycloadditions with electron-deficient olefins. In this report, we reverse this reactivity and drive the 1,3-dipoles to serve as electrophiles by employing 3-alkylated indoles as nucleophiles. This represents the first use of VCPs for the completely atom-economic functionalization of 3-substituted 1H-indoles and tryptophan derivatives via a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA). Excellent yields and high chemo-, regio-, and enantioselectivities have been realized, providing various indolenine and indoline products. The method is amenable to gram scale and works efficiently with tryptophan derivatives that contain a diketopiperazine or diketomorpholine ring, allowing us to synthesize mollenine A in a rapid and ligand-controlled fashion. The obtained indolenine products bear an imine, an internal olefin, and a malonate motif, giving multiple sites with diverse reactivities for product diversification. Complicated polycyclic skeletons can be conveniently constructed by leveraging this unique juxtaposition of functional groups.
