TY - JOUR
T1 - Synthesis and anticonvulsant activity of aromatic tetramethylcyclopropanecarboxamide derivatives
AU - Shimshoni, Jakob Avi
AU - Bialer, Meir
AU - Yagen, Boris
PY - 2008/6/1
Y1 - 2008/6/1
N2 - As part of our ongoing research on potential new antiepileptic drugs (AEDs), a series of tetramethylcyclopropanecarboxamide derivatives containing benzene ring were designed, synthesized, and evaluated for anticonvulsant activities in the murine maximal electroshock (MES) and subcutaneous pentylenetetrazole (scMet) seizure tests. The most potent compound emerging from this study was N-(2,2,3,3-tetramethylcyclopropanecarboxamide)-p-phenyl-sulfonamide (21), possessing an ED50 value of 26 mg/kg in the rat-MES test and a remarkable PI (PI = TD50/ED50) value above 19. The better anticonvulsant potency of compound 21 and its wider safety margin compared to valproic acid (VPA) and zonisamide make it a potential candidate to become a new AED second-generation to VPA.
AB - As part of our ongoing research on potential new antiepileptic drugs (AEDs), a series of tetramethylcyclopropanecarboxamide derivatives containing benzene ring were designed, synthesized, and evaluated for anticonvulsant activities in the murine maximal electroshock (MES) and subcutaneous pentylenetetrazole (scMet) seizure tests. The most potent compound emerging from this study was N-(2,2,3,3-tetramethylcyclopropanecarboxamide)-p-phenyl-sulfonamide (21), possessing an ED50 value of 26 mg/kg in the rat-MES test and a remarkable PI (PI = TD50/ED50) value above 19. The better anticonvulsant potency of compound 21 and its wider safety margin compared to valproic acid (VPA) and zonisamide make it a potential candidate to become a new AED second-generation to VPA.
KW - 2,2,3,3-Tetramethylcyclopropanecarboxylic acid
KW - Anticonvulsants
KW - Maximal electroshock seizure test
KW - Phenyl-alkyl-amines
KW - Structure-activity relationships
KW - Subcutaneous pentylenetetrazole seizure test
KW - Sulfonamides
KW - Valproic acid
UR - http://www.scopus.com/inward/record.url?scp=44449083297&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2008.03.051
DO - 10.1016/j.bmc.2008.03.051
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C2 - 18472270
AN - SCOPUS:44449083297
SN - 0968-0896
VL - 16
SP - 6297
EP - 6305
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 11
ER -