Synthesis and anticonvulsant activity of 8-alkoxy-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1-one derivatives

Piao, Fengyuan; Han, Rongbi; Zhang, Wei; Zhang, Wenbin; Ri-shan, Jiang

doi:10.1016/j.ejmech.2011.01.017

Cited by 18 publications

(6 citation statements)

References 27 publications

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“…These PI values were higher than the PI value of the prototype antiepileptic drug carbamazepine. Sc-PTZ tests showed that 147a was the most potent with ED 50 value of 38.0 mg/kg and PI value of greater than 29.4, which is much safer than marketed drug carbamazepine 169 .…”

Section: Fused-triazolonesmentioning

confidence: 91%

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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Section: Fused-triazolonesmentioning

confidence: 91%

Recent developments on triazole nucleus in anticonvulsant compounds: a review

Song

Deng

2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…This test was chosen because it has a good predictive value for anticonvulsant and antiepileptic activities in the clinic [16, 17]. Mice were divided into 6 groups ( n = 8 per group).…”

Section: Methodsmentioning

confidence: 99%

Monoterpenoid Terpinen-4-ol Exhibits Anticonvulsant Activity in Behavioural and Electrophysiological Studies

Nóbrega

Salvadori

Masson

et al. 2014

Oxidative Medicine and Cellular Longevity

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Terpinen-4-ol (4TRP) is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p.) at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v.) at concentrations of 10, 20, and 40 ng/2 μL. For in vitro experiments, 4TRP concentrations were 0.1 mM and 1.0 mM. 4TRP (i.p.) inhibited pentylenetetrazol- (PTZ-) induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v.) protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP). The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of the GABAA receptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels.

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“…Compound 3 was demethylated by BBr 3 to produce compound 4 , which was reacted with the appropriate alkyl halide to produce the target compounds 5a-5n . The structures of all the new compounds were confi rmed by IR, 1 H NMR, 13 C NMR, MS and elemental analyses, and their anticonvulsant activities have been initially screened.…”

Section: ▼ Chemistrymentioning

confidence: 99%

“…Triazole compounds also have a wide variety of biological activities, and the introduction of a triazole ring to some active molecules may signifi cantly improve the activity of the parent molecule through additive or synergistic eff ects [ 10 -13 ] . We have synthesized a series of 2,3,4,5-tetrahydro-7-alkoxy-1H-2-benzazepin-1-one [ 9 ] and 9-alkoxy-6,7-dihydro-2H-benzo[c] [1,2,4]triazolo [4,3-a]azepin-3(5H)-one derivatives [ 13 ] and evaluated them for their anticonvulsant activity. The most active compound in this series showed moderate anticonvulsant activity.…”

Section: Introduction ▼mentioning

confidence: 99%

“…IR (KBr), cm − 1 : 1 605, 1 464 (C = N, C = C), 1 233 (C-O) 1. H NMR (300 MHz, DMSO-d 6 ): δ 8.57 (1H, s, triazole CH), 7.77 (1H, d, J = 8.4 Hz, ArH), 7.51 (2H, d, J = 8.7 Hz, ArH), 7.47 (2H, d, J = 8.7 Hz, ArH), 7.00-7.09 (2H, m, ArH), 5.17 (2H, s, benzyl CH 2 ), 4.03 (2H, t, J = 6.6 Hz, H-5), 2.70 (2H, t, J = 6.9 Hz, H-7), 2.15-2.26 (2H, m, H-6);13 C NMR (75 MHz, DMSO-d 6 ): δ 159.4 (C-9), 153.4 (C-11b), 144.4 (C-3), 140.4 (C-7a), 135.9 (phenyl C-1), 132.6 (phenyl C-4), 129.9 (C-11), 129.6 (phenyl C-2 and C-6), 128.5 (phenyl C-3 and C-5), 120.0 (C-11a), 116.2 (C-8), 113.2 (C-10), 68.5 (benzyl C), 42.7 (C-5), 31.0 (C-7), 28.4 (C-6). MS-APCI positive (m/z, %): 326.0 ([M + 1] + , 100).…”

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confidence: 99%

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Synthesis and Biological Evaluation of 9-alkoxy-6,7-dihydro-5H-benzo[c] [1,2,4]triazolo[4,3-a]azepines as Potential Anticonvulsant Agents

Piao

Peng

Zhang

et al. 2012

Arzneimittelforschung

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A novel series of 9-alkoxy-6,7-dihydro-5H-benzo[c][1,2,4]triazolo[4,3-a]azepine derivatives was synthesized and screened for anticonvulsant activity by the maximal electroshock (MES) test and the subcutaneous pentylenetetrazol (scPTZ) test. Neurotoxic effects were also determined by the rotarod neurotoxicity test. The results revealed that all of the compounds exhibited anticonvulsant activity, Compound 5d was found to possess the most potential anticonvulsant activity in the anti-MES potency test; it had a median effective dose (ED50) of 12.3 mg/kg, a median toxicity dose (TD50) of 73.5 mg/kg, and a protective index (PI) of 6.0, which is slightly lower than the PI of the prototype drug carbamazepine (ED50=8.8, PI=8.1). In the scPTZ test, compound 5c was the most active, with an ED50 value of 19.8 mg/kg, a TD50 value of 80.8 mg/kg and a PI value of 4.1, which are much greater than the ED50 and the PI of the prototype drug carbamazepine (ED50>100, PI<0.72), Possible structure-activity relationships are also discussed.

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Synthesis and anticonvulsant activity of 8-alkoxy-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1-one derivatives

Cited by 18 publications

References 27 publications

Recent developments on triazole nucleus in anticonvulsant compounds: a review

Recent developments on triazole nucleus in anticonvulsant compounds: a review

Monoterpenoid Terpinen-4-ol Exhibits Anticonvulsant Activity in Behavioural and Electrophysiological Studies

Synthesis and Biological Evaluation of 9-alkoxy-6,7-dihydro-5H-benzo[c] [1,2,4]triazolo[4,3-a]azepines as Potential Anticonvulsant Agents

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