Synthesis and evaluation of 3-(2,4-{Dioxo}-1,3,8-triazaspiro4.6]undec-3-yl) methyl]benzonitrile derivatives as potential anticonvulsants

Madaiah, M. and Prashanth, M. K. and Revanasiddappa, H. D. and Veeresh, B. (2013) Synthesis and evaluation of 3-(2,4-{Dioxo}-1,3,8-triazaspiro4.6]undec-3-yl) methyl]benzonitrile derivatives as potential anticonvulsants. Archiv der Pharmazie, 346 (3). pp. 200-209. ISSN 0365-6233

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Abstract

New 3-(2,4-dioxo-1,3,8-triazaspiro4.6]undec-3-yl)methyl]benzonitrile derivatives 8-37 were synthesized and their pharmacological activities were determined with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity. All the compounds were evaluated for their possible anticonvulsant activity by maximal electroshock seizure (MES) and pentylenetetrazole (PTZ) test. Compounds 11, 18, 31, and 32 showed significant and protective effect on seizure, when compared with the standard drug valproate. The same compounds were found to exhibit advanced anticonvulsant activity as well as lower neurotoxicity than the reference drug. From this study, it is quite apparent that there are at least three parameters for the activity of anticonvulsant drugs, that is, a lipophilic domain, a hydrophobic center, and a two-electron donor. A series of 3-(2,4-Dioxo-1,3,8-triazaspiro4. 6]undec-3-yl)methyl]-benzonitrile derivatives 8-37 were synthesized and evaluated for their anticonvulsant activity. The most promising compounds 11, 18, 31, and 32 showed significant and protective effects on seizure. The novel anticonvulsant agents include essential pharmacophoric elements in their structure.

Item Type:	Article
Uncontrolled Keywords:	article, priority journal, animal experiment, animal model, controlled study, drug screening, nonhuman, unclassified drug, Animals, drug synthesis, structure activity relation, 3, lipophilicity, Dose-Response Relationship, Drug, Molecular Structure, Structure-Activity Relationship, anticonvulsant activity, neurotoxicity, seizure, Nitriles, Mice, mouse, Lethal Dose 50, hydrophobicity, neuroprotection, Drug Design, anticonvulsive agent, unindexed drug, Spiro Compounds, 4 dioxo 1, valproic acid, Anticonvulsants, Electroshock, maximal electroshock seizure, Seizures, competitive inhibition, (2 chlorobenzyl) 3 (3 cyanobenzyl) 2, (4 chlorophenyl) 3 (3 cyanobenzyl) 2, 1 tert butyl 4 ethyl 5 oxoazepane 1, 3 2, 3 8 (2, 3 8 (2 chlorophenyl)sulfonyl 2, 3 8 (2 cyanophenyl)sulfonyl 2, 3 8 (2 fluorophenyl)sulfonyl 2, 3 8 (2 methylphenyl)sulfonyl 2, 3 8 (3, 3 8 (3 bromophenyl)sulfonyl 2, 3 8 (3 fluorophenyl)sulfonyl 2, 3 8 (3 methylphenyl)sulfonyl 2, 3 8 (4 ethylphenyl)sulfonyl 2, 3 8 (4 fluoro 2 methylphenyl)sulfonyl 2, 3 8 (4 methoxyphenyl)sulfonyl 2, 3 8 (4 methylbenzyl)sulfonyl 2, 4 dicarboxylate, 4 dimethylphenyl)sulfonyl 2, 4 dioxo 8 (2 fluorophenyloyl) 1, 4 dioxo 8 (3 fluorophenyloyl) 1, 4 dioxo 8 (3 methylphenyloyl) 1, 4 dioxo 8 (4 methylphenyloyl) 1, 4 dioxo 8 (benzylmethyloyl) 1, 5 dimethylphenyl)sulfonyl 2, 6)undec 3 yl]methyl]benzonitrile, 8 triazaspiro(4, 8 triazaspiro(4.6)undec 3 yl]methyl]benzonitrile, 8 triazaspiro(4.6)undecane 8 carboxylate, GABAergic system, Neurotoxicity Syndromes, tert butyl 2, tert butyl 3 (3 cyanobenzyl) 2, tert butyl 4 oxoazepane 1 carboxylate, tert butyl 4 oxopiperidine 1 carboxylate
Subjects:	C Chemical Science > Chemistry
Divisions:	Department of > Chemistry
Depositing User:	Arshiya Kousar Library Assistant
Date Deposited:	17 Oct 2019 09:42
Last Modified:	17 Oct 2019 09:42
URI:	http://eprints.uni-mysore.ac.in/id/eprint/9193

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