Recent Developments in the Synthesis of Acetylcholinesterase Inhibitors

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.

RP-HPLC determination of lipophilicity in series of quinoline derivatives

“…Some quinoline based compounds showed also antineoplastics, antiasthmatic and antiplatelet activity [5][6][7][8][9][10]. The acetylcholinesterase inhibitory activity of various quinoline derivatives has been tested for potential treatment of nervous diseases [11].…”

Synthesis and Characterization of Tetrahydroquinolines as acetylcholinesterase inhibitors

“…Many quinoline derivatives have shown anti-cholinesterase activity and can be potential agents for treatment of AD (12)(13)(14). Gatta et al in 1992(15) reported the synthesis of THQs derivatives as potential AChEI, Fink et al in 1995(16) reported the synthesis and evaluation of 5-amino-5,6,7,8-tetrahydroquinolinones as AChEI, and in 2012 Maalej et al (17)reported the synthesis, biological assessment, and molecular modeling of racemic 7-aryl-9,10,11,12-tetrahydro-7H-benzo [7,8]chromeno [2,3-b]quinolin-8-amines as potential drugs for the treatment of AD.…”

Synthesis of 9‐amino‐5,6,7,8‐tetrahydrothieno[3,2‐b]quinoline and 9‐amino‐5,6,7,8‐tetrahydrothieno[3,2‐b]quinolin‐8‐ol derivatives

“…Acetylcholinesterase (AChE) inhibitors such as tacrine (1a) and donepezil by ''cholinergic hypothesis'' have been a useful and practical treatment for AD [5,6]. Moreover, the interest for AChE inhibitors has been greatly renewed due to the recent evidences that AChE might function to accelerate b-amyloid peptide (Ab) formation and could play a role during amyloid deposition in AD brain [7,8].…”