Discovery of 1-(1H-indazol-4-yl)-3-((1-phenyl-1H-pyrazol-5-yl)methyl) ureas as potent and thermoneutral TRPV1 antagonists.
Analgesics
/ chemical synthesis
Animals
Body Temperature
/ drug effects
CHO Cells
Capsaicin
/ pharmacology
Cricetulus
Humans
Indazoles
/ chemical synthesis
Methylurea Compounds
/ chemical synthesis
Mice
Molecular Structure
Pyrazoles
/ chemical synthesis
Structure-Activity Relationship
TRPV Cation Channels
/ agonists
Analgesic
TRPV1 Antagonist
Vanilloid Receptor 1
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 12 2020
01 12 2020
Historique:
received:
21
07
2020
revised:
03
09
2020
accepted:
06
09
2020
pubmed:
16
9
2020
medline:
3
7
2021
entrez:
15
9
2020
Statut:
ppublish
Résumé
A series of 1-indazol-3-(1-phenylpyrazol-5-yl)methyl ureas were investigated as hTRPV1 antagonists. The structure-activity relationship study was conducted systematically for both the indazole A-region and the 3-trifluoromethyl/t-butyl pyrazole C-region to optimize the antagonism toward the activation by capsaicin. Among them, the antagonists 26, 50 and 51 displayed highly potent antagonism with K
Identifiants
pubmed: 32931910
pii: S0960-894X(20)30659-4
doi: 10.1016/j.bmcl.2020.127548
pii:
doi:
Substances chimiques
Analgesics
0
Indazoles
0
Methylurea Compounds
0
Pyrazoles
0
TRPV Cation Channels
0
TRPV1 protein, human
0
Capsaicin
S07O44R1ZM
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
127548Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.