Process for the preparation of aminocarbonyl derivatives of geneseroline having selective brain anticholinesterase activity

US6297237A · kind A · utility

Assignee

• Chiesi Farmaceutici S.p.A. · IT

Inventors

• Paolo Chiesi · Parma, IT
• Paolo Ventura · Parma, IT
• Vittorino Servadio · Parma, IT
• Roberto Pighi · Parma, IT
• Fausto Pivetti · Parma, IT
• Bluetta Salsi · Parma, IT
• Maurizio Delcanale · Parma, IT
• Gabriele Amari · Parma, IT
• Claudio Pietra · Como, IT

Key dates

• Filing date: Aug 2, 1999
• Grant date: Oct 2, 2001
• Expiry date: Aug 2, 2019

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A process for the preparation of compounds of formula (I), ##STR1## wherein R is C.sub.2 -C.sub.20 linear or branched alkyl, C.sub.3 -C.sub.7 cycloalkyl, phenyl or benzyl, which can optionally be substituted by C.sub.1 -C.sub.4 alkyl, halogen or C.sub.1 -C.sub.4 alkoxy group, said process comprising: a) oxidation of eserine with hydrogen peroxide in the presence of a base and subsequent hydrolysis to geneseroline, without isolating the intermediate geneserine; b) acylation of geneseroline with an isocyanate of formula R--N.dbd.C.dbd.O, wherein R is as defined above, in the presence of a basic catalyst; c) optional transformation into a pharmaceutically acceptable salt. Compounds of formula (I) wherein R is a phenyl or benzyl, which can be optionally substituted by alkyl, halogen or alkoxy, are selective, potent brain anticholinesterase inhibitors.