Pyrrolinone derivatives as a new class of P2X3 receptor antagonists Part 2: Discovery of orally bioavailable compounds.
Administration, Oral
Biological Availability
Drug Discovery
High-Throughput Screening Assays
Humans
Inhibitory Concentration 50
Neuralgia
/ drug therapy
Purinergic P2X Receptor Antagonists
/ administration & dosage
Pyrroles
/ pharmacology
Receptors, Purinergic P2X3
/ drug effects
Structure-Activity Relationship
Ion channels
P2X3 receptor antagonists
Pain
Purinergic receptors
Pyrrolinone derivatives
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
01 03 2019
01 03 2019
Historique:
received:
21
10
2018
revised:
28
01
2019
accepted:
30
01
2019
pubmed:
8
2
2019
medline:
15
2
2020
entrez:
8
2
2019
Statut:
ppublish
Résumé
Some P2X3 receptor antagonists have been developed as new therapeutic drugs for pain. We discovered a novel chemotype of P2X3 receptor antagonists with a pyrrolinone skeleton. Because of SAR studies to improve bioavailability of lead compound 2, compound (R)-24 was identified, which showed an analgesic effect against neuropathic pain by oral administration. We constructed a human P2X3 homology model as a template for the zebrafish P2X4 receptor, which agreed with SAR studies of pyrrolinone derivatives.
Identifiants
pubmed: 30728111
pii: S0960-894X(19)30060-5
doi: 10.1016/j.bmcl.2019.01.039
pii:
doi:
Substances chimiques
Purinergic P2X Receptor Antagonists
0
Pyrroles
0
Receptors, Purinergic P2X3
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
688-693Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.