Discovery of 7-alkyloxy- [1,2,4] triazolo[1,5-a] pyrimidine derivatives as selective positive modulators of GABAA1 and GABAA4 receptors with potent antiepileptic activity

Wu, Jun; Hou, Zhipeng; Wang, Yan; Chen, Liping; Lian, Chengxi; Meng, Qingfei; Zhang, Chaoying; Li, Xiufen; Huang, Longjiang; Yu, Haibo

doi:10.1016/j.bioorg.2021.105565

Cited by 5 publications

(2 citation statements)

References 46 publications

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“…The study of Gitto et al revealed 1,2,4-triazole-based compounds could inhibit α-syn aggregation to prevent Parkinson’s disease [ 19 ]. Wu et al worked on 1,2,4-triazole derivatives and found a series of anticonvulsant compounds by using epilepsy models during both in vivo and in vitro studies [ 20 ]. Recently, triazole-based compounds have been explored for the possibility of treating AD.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity of 4-(4-(Heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one via Repression of MAPK/NF-κB Signaling Pathways in β-Amyloid-Induced Alzheimer’s Disease Models

Xuan

Liu

et al. 2022

Molecules

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Alzheimer’s disease (AD) is a major neurodegenerative disease, but so far, it can only be treated symptomatically rather than changing the process of the disease. Recently, triazoles and their derivatives have been shown to have potential for the treatment of AD. In this study, the neuroprotective effects of 4-(4-(heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (W112) against β-amyloid (Aβ)-induced AD pathology and its possible mechanism were explored both in vitro and in vivo. The results showed that W112 exhibits a neuroprotective role against Aβ-induced cytotoxicity in PC12 cells and improves the learning and memory abilities of Aβ-induced AD-like rats. In addition, the assays of the protein expression revealed that W112 reversed tau hyperphosphorylation and reduced the production of proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, both in vitro and in vivo studies. Further study indicated that the regulation of mitogen-activated protein kinase/nuclear factor-κB pathways played a key role in mediating the neuroprotective effects of W112 against AD-like pathology. W112 may become a potential drug for AD intervention.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity of 4-(4-(Heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one via Repression of MAPK/NF-κB Signaling Pathways in β-Amyloid-Induced Alzheimer’s Disease Models

Xuan

Liu

et al. 2022

Molecules

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“…By stimulating the ionotropic GABA A , GABA C , and metabotropic GABA B receptors, this neurotransmitter enhances the central inhibitory tone. The glutamate cycle is responsible for synthesis of GABA, an endogenous substance found in GABAergic nerve terminals . It is estimated that GABA is present in 60–70% of all synapses in the central nervous system .…”

Section: Mechanism Of Action Of Antiepileptic Drugsmentioning

confidence: 99%

Anticonvulsant Classes and Possible Mechanism of Actions

Abd-Allah,

El-Mohsen Anwar,

Mohammed

et al. 2023

ACS Chem. Neurosci.

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Epilepsy is considered one of the most common neurological disorders worldwide; it needs long-term or life-long treatment. Despite the presence of several novel antiepileptic drugs, approximately 30% patients still suffer from drug-resistant epilepsy. Subsequently, searching for new anticonvulsants with lower toxicity and better efficacy is still in paramount demand. Using target-based studies in the discovery of novel antiepileptics is uncommon owing to the insufficient information on the molecular pathway of epilepsy and complex mode of action for most of known antiepileptic drugs. In this review, we investigated the properties of anticonvulsants, types of epileptic seizures, and mechanism of action for anticonvulsants.

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Design, synthesis, anticonvulsant activity and structure-activity relationships of novel 7-Azaindole derivatives

Meng

Ren

Wang

et al. 2023

Bioorganic Chemistry

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Discovery of 7-alkyloxy- [1,2,4] triazolo[1,5-a] pyrimidine derivatives as selective positive modulators of GABAA1 and GABAA4 receptors with potent antiepileptic activity

Cited by 5 publications

References 46 publications

Anti-Inflammatory Activity of 4-(4-(Heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one via Repression of MAPK/NF-κB Signaling Pathways in β-Amyloid-Induced Alzheimer’s Disease Models

Anti-Inflammatory Activity of 4-(4-(Heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one via Repression of MAPK/NF-κB Signaling Pathways in β-Amyloid-Induced Alzheimer’s Disease Models

Anticonvulsant Classes and Possible Mechanism of Actions

Design, synthesis, anticonvulsant activity and structure-activity relationships of novel 7-Azaindole derivatives

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