Synthesis and Pharmacological Evaluation of Tetrahydro-γ-carboline Derivatives as Potent Anti-inflammatory Agents Targeting Cyclic GMP-AMP Synthase.
Animals
Anti-Inflammatory Agents
/ chemical synthesis
Autoimmune Diseases
/ drug therapy
Binding Sites
Carbolines
/ chemistry
Cell Survival
/ drug effects
DNA
/ chemistry
Disease Models, Animal
Drug Design
Female
Humans
Interleukin-6
/ genetics
Lipopolysaccharides
/ toxicity
Mice
Mice, Inbred BALB C
Molecular Conformation
Molecular Docking Simulation
Nucleotidyltransferases
/ antagonists & inhibitors
Signal Transduction
/ drug effects
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:
10 06 2021
10 06 2021
Historique:
pubmed:
29
5
2021
medline:
22
6
2021
entrez:
28
5
2021
Statut:
ppublish
Résumé
The activation of cyclic GMP-AMP synthase (cGAS) by double-stranded DNA is implicated in the pathogenesis of many hyperinflammatory and autoimmune diseases, and the cGAS-targeting small molecule has emerged as a novel therapeutic strategy for treating these diseases. However, the currently reported cGAS inhibitors are far beyond maturity, barely demonstrating in vivo efficacy. Inspired by the structural novelty of compound
Identifiants
pubmed: 34044539
doi: 10.1021/acs.jmedchem.1c00398
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Carbolines
0
Interleukin-6
0
Lipopolysaccharides
0
gamma-carboline
244-69-9
DNA
9007-49-2
Nucleotidyltransferases
EC 2.7.7.-
cGAS protein, human
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM