Optimizing drug-like properties of selective butyrylcholinesterase inhibitors for cognitive improvement: Enhancing aqueous solubility by disrupting molecular plane.
Alzheimer's disease
Drug-like property optimization
Pharmacokinetic
Selective butyrylcholinesterase inhibitor
Solubility optimization
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 Mar 2024
15 Mar 2024
Historique:
received:
09
01
2024
revised:
19
02
2024
accepted:
25
02
2024
medline:
18
3
2024
pubmed:
8
3
2024
entrez:
7
3
2024
Statut:
ppublish
Résumé
Most recently, worldwide interest in butyrylcholinesterase (BChE) as a potential target for treating Alzheimer's disease (AD) has increased. In this study, the previously obtained selective BChE inhibitors with benzimidazole-oxadiazole scaffold were further structurally modified to increase their aqueous solubility and pharmacokinetic (PK) characteristics. S16-1029 showed improved solubility (3280 μM, upgraded by 14 times) and PK parameters, including plasma exposure (AUC
Identifiants
pubmed: 38452730
pii: S0223-5234(24)00169-7
doi: 10.1016/j.ejmech.2024.116289
pii:
doi:
Substances chimiques
Butyrylcholinesterase
EC 3.1.1.8
Cholinesterase Inhibitors
0
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
116289Informations de copyright
Copyright © 2024 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.