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Synthesis and Evaluation of 3‐[(2,4‐Dioxo‐1,3,8‐triazaspiro[4.6]undec‐3‐yl)methyl]benzonitrile Derivatives as Potential Anticonvulsants
Author(s) -
Madaiah Malavalli,
Prashanth Maralekere K.,
Revanasiddappa Hosakere D.,
Veeresh Bantal
Publication year - 2013
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201200400
Subject(s) - anticonvulsant , benzonitrile , chemistry , neurotoxicity , seizure threshold , pharmacology , drug , stereochemistry , epilepsy , toxicity , medicinal chemistry , organic chemistry , medicine , psychiatry
Abstract New 3‐[(2,4‐dioxo‐1,3,8‐triazaspiro[4.6]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.