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: Pranjal K Baruah, Jason Dinsmore, Amber M King, Christophe Salomé, Marc De Ryck, Rafal Kaminski, Laurent Provins, Harold Kohn
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 20 Issue 11 Pg. 3551-64 (Jun 01 2012) ISSN: 1464-3391 [Electronic] England
• PMID: 22546207 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Acetamides
• Amino Acids
• Anticonvulsants

Topics

• Acetamides (chemical synthesis, chemistry, pharmacology)
• Amino Acids (chemistry)
• Animals
• Anticonvulsants (chemical synthesis, chemistry, pharmacology)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Male
• Mice
• Mice, Inbred Strains
• Molecular Structure
• Neuralgia (drug therapy)
• Seizures (drug therapy)
• Structure-Activity Relationship