Identification of N-phenyl-3-methoxy-4-pyridinones as orally bioavailable H
- Resource Type
- Authors
- Minkui, Zhang; Li, Tang; Liu, Jiang; Jun, Wei; Yongzhou, Hu; Rong, Sheng
- Source
- European journal of medicinal chemistry. 212
- Subject
- Amyloid beta-Peptides
Dose-Response Relationship, Drug
Molecular Structure
Pyridones
Administration, Oral
Biological Availability
Rats
Molecular Docking Simulation
Rats, Sprague-Dawley
Protein Aggregates
Structure-Activity Relationship
Alzheimer Disease
Animals
Humans
Receptors, Histamine H3
Maze Learning
Histamine H3 Antagonists
- Language
- ISSN
- 1768-3254
Based on our previous work, a series of N-phenyl-3-methoxy-4-pyridinone derivatives were designed as orally bioavailable dual functional agents for therapy of Alzheimer's disease, through introducing alkyloxy moiety into 4-pyridinone ring to avoid the possible phase II metabolism of 3-hydroxy-4-pyridinone in lead compound 3-hydroxy-2-methyl-1-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl)-pyridin-4(1H)-one (4). In vitro studies indicated that most of these compounds exhibit excellent H