α-Fluoro-2,2,3,3-Tetramethylcyclopropanecarboxamide, a Novel Potent Anticonvulsant Derivative of a Cyclic Analogue of Valproic Acid
作者： Neta Pessah , Meir Bialer , Bogdan Wlodarczyk , Richard H. Finnell , Boris Yagen
DOI: 10.1021/JM900017F
关键词:
摘要: 2,2,3,3-Tetramethylcyclopropanecarboxylic acid (TMCA, 4) is a cyclic analogue of the antiepileptic drug (AED) valproic (VPA) (1). α-F, α-Cl, α-Br, and α-methyl derivatives 4 their amides were synthesized tested in rodent models for anticonvulsant potency AED-induced teratogenicity. In rat-maximal electroshock (MES) subcutaneous metrazol (scMet) tests, α-Cl-TMCD (17) had ED50 values 97 27 mg/kg, respectively. α-F-TMCD (11) was 120 times more potent than VPA rat-scMet test (ED50 = 6 mg/kg) protective index (PI TD50/ED50) 20. Hz psychomotor mouse model 11 57 mg/kg (32 mA) 59 (44 mA). The hippocampal-kindled rat pilocarpine-induced-status 30 23 Unlike 1, nonteratogenic mice. This novel compound has potential to become candidate development as new safe CNS drug.
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