title: Synthesis and evaluation of 3-[(2,4-dioxo-1,3,8-triazaspiro[4.6]undec-3-yl)methyl]benzonitrile derivatives as potential anticonvulsants.
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.
authors: Department of Chemistry, University of Mysore, Manasagangotri, Mysore, India.
authors: Malavalli
authors: M
authors: Madaiah
authors: Maralekere K
authors: MK
authors: Prashanth
authors: Hosakere D
authors: HD
authors: Revanasiddappa
authors: Bantal
authors: B
authors: Veeresh
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004597:Electroshock; D007928:Lethal Dose 50; D051379:Mice; D015394:Molecular Structure; D020258:Neurotoxicity Syndromes / Q000209:etiology; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D012640:Seizures / Q000188:drug therapy; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D013141:Spiro Compounds; C014356:benzonitrile