Synthesis and antidepressant-like activity of novel alkoxy-piperidine derivatives targeting SSRI/5-HT1A/5-HT7

Wang, Wen-Tao; Qian, Hao; Wu, Jianwei; Chen, Xiaowen; Li, Jianqi

doi:10.1016/j.bmcl.2019.126769

Cited by 14 publications

(6 citation statements)

References 21 publications

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“…Twenty-five studies that used compounds nonspecific to the 5-HT7 receptor identified potential antidepressant effects depression such as immobility time, in both the FST or TST ( Abbas et al, 2009 ; Cates et al, 2013 ; Chlon-Rzepa et al, 2013 ; Gu et al, 2019 , 2018 , 2017 ; Guilloux et al, 2013 ; Jankowska et al, 2020 ; Kim et al, 2014 ; Kołaczkowski et al, 2014 ; Latacz et al, 2018 ; Li et al, 2013 ; Mørk et al, 2012 ; Partyka et al, 2017 , 2019 ; Pytka et al, 2015 , 2017a , 2017b , 2018 ; Wang et al, 2019 ; Waszkielewicz et al, 2015 ; Wróbel et al, 2019 ; Zagórska et al, 2015 , 2016 ; Zajdel et al, 2013 ).…”

Section: Preclinical Study Resultsmentioning

confidence: 99%

“…Two studies found mixed results, each with a 5-HT7 antagonist compound showing potential antidepressant effects in the FST, but not TST ( Lax et al, 2018 ; Wang et al, 2019 ). A further three studies showed no significant antidepressant effects of their tested compounds in either the TST or FST ( Delcourte et al, 2017 ; Maxwell et al, 2019 ; Volk et al, 2011 ).…”

Section: Preclinical Study Resultsmentioning

confidence: 99%

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The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: A systematic review

Gottlieb,

Li,

Young

et al. 2023

J Psychopharmacol

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Background: Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this systematic review, we aimed to review the relationship between the 5-HT7 receptor system and mood and anxiety disorders, and to explore the pharmacology and therapeutic potential of medications that target the 5-HT7 receptor for their treatment. Methods: Medline, Cochrane Library, EMBASE, PsycINFO databases, the National Institute of Health website Clinicaltrials.gov, controlled-trials.com, and relevant grey literature were used to search for original research articles, and reference lists of included articles were then hand searched. Results: Sixty-four studies were included in the review: 52 animal studies and 12 human studies. Studies used a variety of preclinical paradigms and questionnaires to assess change in mood, and few studies examined sleep or cognition. Forty-four out of 47 (44/47) preclinical 5-HT7 modulation studies identified potential antidepressant effects and 20/23 studies identified potential anxiolytic effects. In clinical studies, 5/7 identified potential antidepressant effects in major depressive disorder, 1/2 identified potential anxiolytic effects in generalized anxiety disorder, and 3/3 identified potential antidepressant effects in bipolar disorders. Conclusion: While there is some evidence that the 5-HT7 receptor system may be a potential target for treating mood and anxiety disorders, many agents included in the review also bind to other receptors. Further research is needed using drugs that bind specifically to 5-HT7 receptors to examine treatment proof of concept further.

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Section: Preclinical Study Resultsmentioning

confidence: 99%

Section: Preclinical Study Resultsmentioning

confidence: 99%

The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: A systematic review

Gottlieb,

Li,

Young

et al. 2023

J Psychopharmacol

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“…7) also displayed dual binding towards 5-HT 1A /SERT with Ki values of 7.0 nM (5-HT 1A ) and 17.5 nM (SERT) for compound 37 as well as 4.9 nM (5-HT 1A ) and 17.5 nM (SERT) for compound 38 over 15 days. In vivo FST assays also identified the lead compound MW005 (30) as the most active due to its good binding ability to the 5-HT 1A receptor and strong antidepressant activity. Therefore compound 30 was identified as the lead compound.…”

Section: Pyrrolidinementioning

confidence: 99%

Development of heterocyclic-based frameworks as potential scaffold of 5-HT1A receptor agonist and future perspectives: A review

Yuan,

Ma,

Zhang

2024

Medicine

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As a subtype of the 5-hydroxytryptamine (5-HT) receptor, 5-HT1A receptors are involved in the pathological process of psychiatric disorders and is an important target for antidepressants. The research groups focus on these area have tried to design novel compounds to alleviate depression by targeting 5-HT1A receptor. The heterocyclic structures is an important scaffold to enhance the antidepressant activity of ligands, including piperazine, piperidine, benzothiazole, and pyrrolidone. The current review highlights the function and significance of nitrogen-based heterocyclics 5-HT1AR represented by piperazine, piperidine, benzothiazole, and pyrrolidone in the development of antidepressant.

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“…Results indicated that two compounds significantly reduced the immobility time at the dose of 40 mg/kg as compared to vortioxetine (reference), and exhibited potent antidepressant-like activity. Metabolic stability assay was performed on the rat liver in which the compounds 6a and 6b displayed a half-life of 34.5 and 22.9 min, which was higher than the standard drug vortioxetine [ 104 ]. The design strategy and SAR studies of these compounds are shown in Fig.…”

Section: Various Classes Of Multi-target Directed Ligands Against Dep...mentioning

confidence: 99%

Design Strategies, Chemistry and Therapeutic Insights of Multi-target Directed Ligands as Antidepressant Agents

Singh

Bhatia

Kumar

et al. 2022

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: Depression is one of the major disorders of the central nervous system worldwide and causes disability and functional impairment. According to the World Health Organization, around 265 million people worldwide are affected by depression. Currently marketed antidepressant drugs take weeks or even months to show anticipated clinical efficacy but remain ineffective in treating suicidal thoughts and cognitive impairment. Due to its multifactorial complexity, single-target drugs did not always produce satisfactory results and lacks the desired level of therapeutic efficacy. Recent literature reports revealed improved therapeutic potential of multi-target directed ligands due to their synergistic potency and better safety. Medicinal chemists have gone to great extents for the design of multi-target ligands by generating structural hybrids of different key pharmacophores with improved binding affinities and potency towards different receptors or enzymes. This article compiled the design strategies of recently published multi-target directed ligands as antidepressant agents. Their biological evaluation, structural-activity relationships, mechanistic and in silico studies were also described. This article will be highly useful for the researchers to design and develop multi-target ligands as antidepressants with high potency and therapeutic efficacy.

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Synthesis and antidepressant-like activity of novel alkoxy-piperidine derivatives targeting SSRI/5-HT1A/5-HT7

Cited by 14 publications

References 21 publications

The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: A systematic review

The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: A systematic review

Development of heterocyclic-based frameworks as potential scaffold of 5-HT1A receptor agonist and future perspectives: A review

Design Strategies, Chemistry and Therapeutic Insights of Multi-target Directed Ligands as Antidepressant Agents

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