Novartis rivastigmine

An interesting approach to the generation of l4C-labeled rivastigmine needed for in vivo studies was published by Novartis (Scheme 11).57 The synthesis of 14C-labeled 2 was initiated by l4C-labeled cyanation of iodide 48 to provide 3-methoxybenzo-14C-nitrile (49) in 80% yield. Copper-mediated addition of methyl magnesium bromide to nitrile 49 formed an imine that was hydrolyzed with aqueous HC1 to the corresponding... 

Based on the in-vitro data in the table, the N-methyl-N-ethyl compound (Entry 6) does not seem to be the best candidate. In fact, it seems to be positioned on the line between the N,N-dimethyl and the barely active N,N-diethyl compounds. It was the in-vivo activities, including the better oral absorption and the much longer duration of action, that first placed it at the top of the group. The enantiomeric mixture, that first attracted Stedman to miotine, was resolved for the methylethyl compound, and the more active enantiomer, S, was developed by Novartis into the AD drug rivastigmine (Exelon ) [40]. 

Novartis Pharmaceuticals. Exelon (rivastigmine tartrate) package insert. East Hanover, NJ, 2001. 

Exelon (Rivastigmine hydrogen tartrate). Novartis Pharmaceuticals UK Ltd. UK Summary of product characteristics, October 2006. 

Exelon (Rivastigmine tartrate). Novartis Pharmaceuticals Corp. US Prescribing information, June 2006. 

Product information Exelon(R), rivastigmine. East Hanover, NJ Novartis. 

Rivastigmine (sold as its tartrate salt under the trade name Exelon Novartis, Basel, Switzerland) is an acetylcholinesterase inhibitor of the carbamate type whose (S)-enantiomer is prescribed for the treatment of mild-to-moderate Alzheimer-type dementia. Gotor-Fernandez, Gotor, and co-workers have reported on a DKR-based... 

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