Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments.
Bioorg Chem
; 93: 103322, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31585263
ABSTRACT
Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62â¯nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain substitution indicates a new binding mode of inhibitor with AChE. This finding provides new insights into the binding mechanism and is helpful for discovery of novel high-activity AChE inhibitors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Acetilcolinesterasa
/
Piridinas
/
Diseño de Fármacos
/
Quelantes
/
Inhibidores de la Colinesterasa
/
Cobre
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2019
Tipo del documento:
Article