title: Synthesis, anticonvulsant activity, and neuropathic pain-attenuating activity of N-benzyl 2-amino-2-(hetero)aromatic acetamides.
abstract: N-Benzyl 2-acetamido-2-substituted acetamides, where the 2-substituent is a (hetero)aromatic moiety, are potent anticonvulsants. We report the synthesis and whole animal pharmacological evaluation of 16 analogues where the terminal 2-acetyl group was removed to give the corresponding primary amino acid derivatives (PAADs). Conversion to the PAAD structure led to a substantial drop in seizure protection in animal tests, demonstrating the importance of the N-acetyl moiety for anticonvulsant activity. However, several of the PAADs displayed notable pain-attenuating activities in a mouse model.
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA.
authors.forename: Pranjal K
authors.initials: PK
authors.lastname: Baruah
authors.forename: Jason
authors.initials: J
authors.lastname: Dinsmore
authors.forename: Amber M
authors.initials: AM
authors.lastname: King
authors.forename: Christophe
authors.initials: C
authors.lastname: Salomé
authors.forename: Marc
authors.initials: M
authors.lastname: De Ryck
authors.forename: Rafal
authors.initials: R
authors.lastname: Kaminski
authors.forename: Laurent
authors.initials: L
authors.lastname: Provins
authors.forename: Harold
authors.initials: H
authors.lastname: Kohn
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009437:Neuralgia / Q000188:drug therapy*; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000596:Amino Acids; D000927:Anticonvulsants