Synthesis and anticonvulsant activity of 7-phenyl-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones and their derivatives

Deng, Xian‐Qing; Quan, Lina; Song, Mo; Wei, Cheng‐Xi; Quan, Zhe‐Shan

doi:10.1016/j.ejmech.2011.04.020

Cited by 32 publications

(15 citation statements)

References 27 publications

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“…To understand the molecular basis of anticonvulsant activity of the newly designed series of pyrimidine–triazine derivatives ( 4a–t) and to explore the binding mechanisms of these molecules, we docked these molecules into the active site of GABA A receptor (PDB ID‐4COF). The active site of GABA A receptor consists of Arg142, Pro144, Leu145, Asp146, Glu147, Gln185, Ser187, Lys215, Arg216, Asn217, Ile218, Asn439, Arg142, Glu147, Asn217, Leu145, Lys215, Asp146, Trp443, Tyr446, and Val447 . Similar to carbamazepine, a marketed GABA A inhibitor, 16 of our synthesized molecules also showed the conserved H‐bond interaction with Arg216 which is a gate‐keeper residue in the GABA A active site.…”

Section: Resultsmentioning

confidence: 76%

“…The preclinical discovery and development of a new chemical entity as an anticonvulsant agent is a great challenge in the field of medicinal chemistry. The development of a new anticonvulsant compound is completely based on the use of proposed animal models . The anticonvulsant activity of the target compounds was evaluated against two standard animal seizure models; one is electrically induced seizure model, that is, maximal electroshock (MES)‐induced seizures, and other is chemically induced seizure model, that is, subcutaneous pentylenetetrazole (scPTZ)‐induced seizures.…”

Section: Resultsmentioning

confidence: 99%

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Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

Sahu

Siddiqui

Naim

et al. 2017

Archiv der Pharmazie

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A series of new pyrimidine-triazine hybrids (4a-t) was designed and synthesized, from which potent anticonvulsant agents were identified. Most of the compounds exhibited promising anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests, along with minimal motor impairment with higher safety compared to the standard drugs, phenytoin and carbamazepine. In the series, 5-(4-(4-fluorophenyl)-6-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4o) and 5-(6-(4-hydroxy-3-methoxyphenyl)-4-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4s) emerged as most potent anticonvulsant agents with median doses of 22.54 and 29.40 mg/kg (MES ED ), 285.02 and 293.42 mg/kg (scPTZ ED ), and 389.11 and 412.16 mg/kg (TD ), respectively. Docking studies were also performed for all synthesized compounds to get insight into the binding pattern toward the GABA receptor as a possible mechanism of their anticonvulsant action, and in silico ADME studies were carried out to predict the safety and stability of the molecules. The increased GABA level in the experimental animals in the neurochemical estimation assay confirmed their GABAergic modulating activity. The most potent compounds were also evaluated for their neurotoxic and hepatotoxic effects. Fortunately, they did not show any sign of neurotoxicity or hepatotoxicity, suggesting that they have a broad spectrum of anticonvulsant activity with a large safety margin. Together, this research suggested that 4o and 4s may serve as leads in the discovery and development of new anticonvulsant drugs.

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Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

Sahu

Siddiqui

Naim

et al. 2017

Archiv der Pharmazie

View full text Add to dashboard Cite

show abstract

“…have repoted synthesis of several triazolo[1,5- a ]pyrimidin-5(4 H )-ones 149 ( Fig. 34 ) as anticonvulsant agents [ 135 ]. SAR study indicated the significance of position of halogen on phenyl ring on the anticonvulsant activity.…”

Section: Biological Activities Of 124-triazole Derivativesmentioning

confidence: 99%

An insight on medicinal attributes of 1,2,4-triazoles

Aggarwal

Sumran²

2020

European Journal of Medicinal Chemistry

199

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The present review aims to summarize the pharmacological profile of 1,2,4-triazole, one of the emerging privileged scaffold, as antifungal, antibacterial, anticancer, anticonvulsant, antituberculosis, antiviral, antiparasitic, analgesic and anti-inflammatory agents, etc. along with structure-activity relationship. The comprehensive compilation of work carried out in the last decade on 1,2,4-triazole nucleus will provide inevitable scope for researchers for the advancement of novel potential drug candidates having better efficacy and selectivity.

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“…Most of the synthesised compounds exhibited potent anticonvulsant activities in the MES test. The most promising compound ( 108 , Figure 17 ) showed significant anticonvulsant activity in MES test with ED 50 value of 19.7 mg/kg and low toxicity in rotarod test with TD 50 value of 684.7 mg/kg, which gave a high PI value of 34.8 127 .…”

Section: Fused-triazolesmentioning

confidence: 99%

Recent developments on triazole nucleus in anticonvulsant compounds: a review

Song

Deng

2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Epilepsy is one of the common diseases seriously threatening life and health of human. More than 50 million people are suffering from this condition and anticonvulsant agents are the main treatment. However, side effects and intolerance, and a lack of efficacy limit the application of the current anticonvulsant agents. The search for new anticonvulsant agents with higher efficacy and lower toxicity continues to be the focus and task in medicinal chemistry. Numbers of triazole derivatives as clinical drugs or candidates have been frequently employed for the treatment of various types of diseases, which have proved the importance of this heterocyclic nucleus in drug design and discovery. Recently many endeavours were made to involve the triazole into the anticonvulsants design, which have brought lots of active compounds. This work is an attempt to systematically review the research of triazole derivatives in the design and development of anticonvulsant agents during the past two decades.

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Synthesis and anticonvulsant activity of 7-phenyl-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones and their derivatives

Cited by 32 publications

References 27 publications

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

An insight on medicinal attributes of 1,2,4-triazoles

Recent developments on triazole nucleus in anticonvulsant compounds: a review

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