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
Mini-Reviews in Medicinal Chemistry
Title: Recent Developments in the Synthesis of Acetylcholinesterase Inhibitors
Volume: 3 Issue: 6
Author(s): Jose L. Marco and M. Carmo Carreiras
Affiliation:
Keywords: tacrine analogues, buche inhibitors, pyrano[2,3-b]quinolines, naphthyridines, quinolines, pyridines
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.
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Cite this article as:
Marco L. Jose and Carreiras Carmo M., Recent Developments in the Synthesis of Acetylcholinesterase Inhibitors, Mini-Reviews in Medicinal Chemistry 2003; 3 (6) . https://dx.doi.org/10.2174/1389557033487908
DOI https://dx.doi.org/10.2174/1389557033487908 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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