Recent Developments in the Synthesis of Acetylcholinesterase Inhibitors

Author(s): Jose L. Marco, M. Carmo Carreiras

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 3 , Issue 6 , 2003


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Abstract:

The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3- b]quinolines (11-13) / 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4- amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15) / 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl- 5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described. These compounds are tacrine analogues that have been prepared from readily available polyfunctionalized ethyl [6-amino-5-cyano-4H-pyran]-3-carboxylates (9, 10), ethyl [6-amino-5-cyanopyridine]-3-carboxylates (7, 8), 2-amino-3-cyano-4,5-diarylfurans (17-19) and 2- amino-3-cyano-4,5-diphenylthiophene (20) via Friedländer condensation with selected ketones. These compounds are competitive and, in a few cases, non-competitive inhibitors for AChE, the most potent being compound (14), though three-fold less active than tacrine. The BuChE inhibitory activity is only significant in compounds 11 and 14, ten-fold less active than tacrine. Furthermore, the products 12 and 13 are selective and moderate AChE inhibitors.

Keywords: tacrine analogues, buche inhibitors, pyrano[2,3-b]quinolines, naphthyridines, quinolines, pyridines

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Article Details

VOLUME: 3
ISSUE: 6
Year: 2003
Page: [518 - 524]
Pages: 7
DOI: 10.2174/1389557033487908
Price: $65

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