Discovery and Structure Relationships of Salicylanilide Derivatives as Potent, Non-acidic P2X1 Receptor Antagonists.
Allosteric Regulation
/ drug effects
Astrocytes
/ cytology
Binding Sites
Blood Platelets
/ cytology
Calcium
/ metabolism
Cell Line
Collagen
Drug Evaluation, Preclinical
Humans
Molecular Dynamics Simulation
Platelet Aggregation
/ drug effects
Protein Isoforms
/ antagonists & inhibitors
Purinergic P2X Receptor Antagonists
/ chemistry
Receptors, Purinergic P2X1
/ chemistry
Salicylanilides
/ chemistry
Structure-Activity Relationship
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
11 06 2020
11 06 2020
Historique:
pubmed:
30
4
2020
medline:
13
11
2020
entrez:
30
4
2020
Statut:
ppublish
Résumé
Antagonists for the ATP-gated ion channel receptor P2X1 have potential as antithrombotics and for treating hyperactive bladder and inflammation. In this study, salicylanilide derivatives were synthesized based on a screening hit. P2X1 antagonistic potency was assessed in 1321N1 astrocytoma cells stably transfected with the human P2X1 receptor by measuring inhibition of the ATP-induced calcium influx. Structure-activity relationships were analyzed, and selectivity versus other P2X receptor subtypes was assessed. The most potent compounds,
Identifiants
pubmed: 32345019
doi: 10.1021/acs.jmedchem.0c00435
doi:
Substances chimiques
Protein Isoforms
0
Purinergic P2X Receptor Antagonists
0
Receptors, Purinergic P2X1
0
Salicylanilides
0
Collagen
9007-34-5
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM