| Title : Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors - Wang_2015_Bioorg.Med.Chem.Lett_25_5212 |
| Author(s) : Wang C , Wu Z , Cai H , Xu S , Liu J , Jiang J , Yao H , Wu X , Xu J |
| Ref : Bioorganic & Medicinal Chemistry Lett , 25 :5212 , 2015 |
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Abstract :
A series of novel 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors have been designed and synthesized. The screening results showed that most of the compounds exhibited potent anti-AChE activity in the range of nM concentrations. The 1-(4-fluorobenzyl) substituted derivative 9d exhibited the most potent anti-AChE activity with IC50 value of 8.9nM and high AChE/BuChE selectivity (SI>230). Kinetic and molecular modeling studies suggested that compound 9d was mixed-type inhibitor, binding simultaneously to CAS and PAS of AChE. Besides, the preliminary structure-activity relationships were discussed. |
| PubMedSearch : Wang_2015_Bioorg.Med.Chem.Lett_25_5212 |
| PubMedID: 26454504 |
Wang C, Wu Z, Cai H, Xu S, Liu J, Jiang J, Yao H, Wu X, Xu J (2015)
Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors
Bioorganic & Medicinal Chemistry Lett
25 :5212
Wang C, Wu Z, Cai H, Xu S, Liu J, Jiang J, Yao H, Wu X, Xu J (2015)
Bioorganic & Medicinal Chemistry Lett
25 :5212