Synthesis and pharmacological evaluation of novel 1'-[2-(difluoromethoxy)benzyl]-2'H,5'H-spiro[8-azabicyclo[3.2.1]octane-3,4'-imidazolidine]-2',5'-diones and their derivatives.
A series of novel 1'-[2-(difluoromethoxy)benzyl]-2'H,5'H-spiro[8-azabicyclo[3.2.1]octane-3,4'-imidazolidine]-2',5'-dione substituted hydantoins (5-32) were synthesized using an appropriate synthetic route and characterized by elemental analysis and spectral data. The novel molecules were screened for anticonvulsant activity in mice by maximal electroshock (MES) and subcutaneous pentylenetetrazol (ScPTZ)-induced seizure tests. The neurotoxicity was assessed using the rotarod method. Compounds 9, 10, 18, 30, and 31 exhibited anticonvulsant potency against MES seizure and in the ScPTZ model, with lesser neurotoxicity. Some title compounds showed lesser central nervous system depression compared to phenytoin.
Department of Chemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
Malavalli
M
Madaiah
Maralekere K
MK
Prashanth
Hosakere D
HD
Revanasiddappa
Bantal
B
Veeresh
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D045442:Rotarod Performance Test; D012640:Seizures / Q000188:drug therapy; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity
D000927:Anticonvulsants; D053961:Azabicyclo Compounds; D048289:Imidazolidines; D013141:Spiro Compounds
Anticonvulsant; Isocyanate; Maximal electroshock; ScPTZ; Spirohydantoins