Anti-narcoleptic agent modafinil and its sulfone: a novel facile synthesis and potential anti-epileptic activity.
We report a facile procedure to synthesize racemic modafinil (diphenylmethylsulfinylacetamide), which is now being used in pharmacotherapy, and its achiral oxidized derivative (diphenylmethylsulfonyl acetamide). Modafinil is of interest more than for its potential anti-narcoleptic activity. It has also been reported to have neuroprotective properties and may potentially be effective in the enhancement of vigilance and cognitive performance. Finally, it may also protect from subclinical seizures that have been implicated as causative factors in autistic spectrum disorders and other neurodegenerative conditions. This agent can now be synthesized simply and in larger amounts than previously, making it more readily available for testing in various research modalities. The described procedure also lends itself to production of several other amides of potential interest. We are currently in the process of synthesizing and testing several new derivatives in this series. The anticonvulsant properties of modafinil and its sulfone derivative have not previously been extensively described in the literature. It may be of interest to note that the oxidized derivative of modafinil is also nontoxic and almost as effective as an anticonvulsant as the parent.
Chatterjie
Nithiananda
N
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. chemexp@aol.com
Stables
James P
JP
Wang
Hsin
H
Alexander
George J
GJ
D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D007202:Indicators and Reagents; D051379:Mice; D000077408:Modafinil; D051381:Rats; D012640:Seizures / Q000517:prevention & control; D013450:Sulfones / Q000494:pharmacology*
D000927:Anticonvulsants; D001559:Benzhydryl Compounds; D007202:Indicators and Reagents; D013450:Sulfones; D000077408:Modafinil