Development of pyrazole and spiropyrazoline analogs as multifunctional agents for treatment of Alzheimer's disease.
Acetylcholinesterase
/ chemistry
Adjuvants, Anesthesia
/ toxicity
Alzheimer Disease
/ drug therapy
Amnesia
/ chemically induced
Animals
Antioxidants
/ chemistry
Benzamides
/ chemistry
Blood-Brain Barrier
/ drug effects
Cholinesterase Inhibitors
/ chemistry
Disease Models, Animal
Drug Design
Female
Mice
Pyrazoles
/ chemistry
Rats
Rats, Wistar
Scopolamine
/ toxicity
Structure-Activity Relationship
Acetylcholinesterase
Alzheimer’s disease
Amyloid beta
Central nervous system
De novo drug design
Spiropyrazoline
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
17
04
2019
revised:
11
05
2019
accepted:
18
06
2019
pubmed:
5
7
2019
medline:
21
10
2020
entrez:
5
7
2019
Statut:
ppublish
Résumé
Cholinergic hypothesis of Alzheimer's disease has been advocated as an essential tool in the last couple of decades for the drug development. Here in, we report de novo fragment growing strategy for the design of novel 3,5-diarylpyrazoles and hit optimization of spiropyrazoline derivatives as acetyl cholinesterase inhibitors. Both type of scaffolds numbering forty compounds were synthesized and evaluated for their potencies against AChE, BuChE and PAMPA. Introduction of lipophilic cyclohexane ring in 3,5-diarylpyrazole analogs led to spiropyrazoline derivatives, which facilitated and improved the potencies. Compound 44 (AChE = 1.937 ± 0.066 µM; BuChE = 1.166 ± 0.088 µM; hAChE = 1.758 ± 0.095 µM; P
Identifiants
pubmed: 31271946
pii: S0045-2068(19)30593-0
doi: 10.1016/j.bioorg.2019.103080
pii:
doi:
Substances chimiques
Adjuvants, Anesthesia
0
Antioxidants
0
Benzamides
0
Cholinesterase Inhibitors
0
Pyrazoles
0
Scopolamine
DL48G20X8X
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103080Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.