(2015) New tetracyclic tacrine analogs containing pyrano2,3-cpyrazole: Efficient synthesis, biological assessment and docking simulation study. European Journal of Medicinal Chemistry. pp. 296-303.
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Abstract
A new series of tacrine-based acetylcholinesterase (AChE) inhibitors 7a-l were designed by replacing the benzene ring of tacrine with aryl-dihydropyrano2,3-cpyrazole. The poly-functionalized hybrid molecules 7a-l were efficiently synthesized through multi-component reaction and subsequent Friedländer reaction between the obtained pyrano2,3-cpyrazoles and cyclohexanone. Most of target compounds showed potent and selective anti-AChE activity at sub-micromolar range. The most potent compound 7h bearing a 3,4-dimethoxyphenyl group was more active than reference drug tacrine. The representative compound 7h could significantly protect neurons against oxidative stress as potent as quercetin at low concentrations. The docking study of compound 7h with AChE enzyme revealed that the (R)-enantiomer binds preferably to CAS while the (S)-enantiomer prone to be a PAS binder. © 2014 Published by Elsevier Masson SAS.
| Item Type: | Article |
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| Keywords: | 3 methyl 4 (3 nitrophenyl) 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 3 methyl 4 (4 tolyl) 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 3 methyl 4 (naphthalen 1 yl) 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 3 methyl 4 (thiophen 1 yl) 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 4 (2 fluorophenyl) 3 methyl 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 4 (2 methoxyphenyl) 3 methyl 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 4 (2,3 dichlorophenyl) 3 methyl 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 4 (2,5 dimethoxyphenyl) 3 methyl 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 4 (3,4 dimethoxyphenyl) 3 methyl 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 4 (3,4,5 trimethoxyphenyl) 3 methyl 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 4 (4 fluorophenyl) 3 methyl 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; 4 (4 methoxyphenyl) 3 methyl 2,4,6,7,8,9 hexahydropyrazolo4',3':5,6pyrano2,3 bquinolin 5 amine; acetylcholinesterase; benzene; cholinesterase; cholinesterase inhibitor; pyrano2,3 c pyrazole derivative; pyrazole derivative; quercetin; tacrine; tacrine derivative; unclassified drug; cholinesterase inhibitor; fused heterocyclic rings; hydrogen peroxide; neuroprotective agent; pyran derivative; pyrazole derivative; tacrine, Article; cell viability; cholinesterase inhibition; controlled study; drug synthesis; enzyme inhibition; neuroprotection; oxidative stress; PC12 cell line; analogs and derivatives; animal; blood; cell death; chemistry; drug design; drug effects; Electrophorus; horse; kinetics; molecular docking; rat; synthesis, Animals; Butyrylcholinesterase; Cell Death; Cholinesterase Inhibitors; Drug Design; Electrophorus; Heterocyclic Compounds with 4 or More Rings; Horses; Hydrogen Peroxide; Kinetics; Molecular Docking Simulation; Neuroprotective Agents; PC12 Cells; Pyrans; Pyrazoles; Rats; Tacrine |
| Page Range: | pp. 296-303 |
| Journal or Publication Title: | European Journal of Medicinal Chemistry |
| Volume: | 89 |
| Publisher: | Elsevier Masson SAS |
| Depositing User: | ms soheila Bazm |
| URI: | http://eprints.ssu.ac.ir/id/eprint/9417 |
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