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Synthesis of Valproic Acid Amides of a Melatonin Derivative, a Piracetam and Amantadine for Biological Tests

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Abstract

Three new amide derivatives of valproic acid have been synthesized and characterized by spectrophotometric studies. The rationale for the preparation of such agents has been based on the observation that chemical combination of the anticonvulsant pharmacophore, valproic acid with amine moieties produces more effective and less toxic amides. The amine components selected in this work also exhibit neuroactivity with the prospect of these agents being biologically active in controlling not just seizures and but also possessing neuroprotective properties. We report here the synthesis and properties of the valproylamides of 5-methoxytryptamine, related to melatonin (1), of N-substituted 2-pyrrolidinone related to piracetam (2), and of adamantylamine related to amantadine (3). In preliminary tests these compounds showed low toxicity and a variety of anticonvulsive properties, including a delay in onset of activity. These compounds and their derivatives are now available to be tested additionally for control of subclinical seizures, enhancement of cognition, behavior modification and alleviation of symptoms and disorders due to neuronal damage.

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Authors and Affiliations

  1. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314

    Nithiananda Chatterjie & George Alexander

  2. The College of Staten Island, The City University of New York, 2800 Victory Boulevard, Staten Island, NY, 10314

    Hsin Wang

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  1. Nithiananda Chatterjie
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  2. George Alexander
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Chatterjie, N., Alexander, G. & Wang, H. Synthesis of Valproic Acid Amides of a Melatonin Derivative, a Piracetam and Amantadine for Biological Tests. Neurochem Res 26, 1171–1176 (2001). https://doi.org/10.1023/A:1012383125480

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  • DOI: https://doi.org/10.1023/A:1012383125480

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