Recent Developments in the Synthesis of Acetylcholinesterase Inhibitors

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.

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