| Title : Design, synthesis and biological evaluation of tricyclic pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one scaffolds as selective BuChE inhibitors - Qiu_2018_J.Enzyme.Inhib.Med.Chem_33_1506 |
| Author(s) : Qiu GL , He SS , Chen SC , Li B , Wu HH , Zhang J , Tang WJ |
| Ref : J Enzyme Inhib Med Chem , 33 :1506 , 2018 |
|
Abstract :
Based on the structural analysis of tricyclic scaffolds as butyrylcholinesterase (BuChE) inhibitors, a series of pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one derivatives were designed, synthesized and evaluated for their acetylcholinesterase (AChE) and BuChE inhibitory activity. Compounds with 5-carbonyl and 7- or/and 9-halogen substitutions showed potential BuChE inhibitory activity, among which compounds 6a, 6c and 6g showed the best BuChE inhibition (IC50 = 1.06, 1.63 and 1.63 microM, respectively). The structure-activity relationship showed that the 5-carbonyl and halogen substituents significantly influenced BuChE activity. Compounds 6a and 6g were found nontoxic, lipophilic and exhibited remarkable neuroprotective activity and mixed-type inhibition against BuChE (Ki = 7.46 and 3.09 microM, respectively). Docking studies revealed that compound 6a can be accommodated into BuChE via five hydrogen bonds, one Pi-Sigma interaction and three Pi-Alkyl interactions. |
| PubMedSearch : Qiu_2018_J.Enzyme.Inhib.Med.Chem_33_1506 |
| PubMedID: 30284486 |
Qiu GL, He SS, Chen SC, Li B, Wu HH, Zhang J, Tang WJ (2018)
Design, synthesis and biological evaluation of tricyclic pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one scaffolds as selective BuChE inhibitors
J Enzyme Inhib Med Chem
33 :1506
Qiu GL, He SS, Chen SC, Li B, Wu HH, Zhang J, Tang WJ (2018)
J Enzyme Inhib Med Chem
33 :1506