Synthesis, evaluation and docking of novel pyrazolo pyrimidines as potent p38α MAP kinase inhibitors with improved anti-inflammatory, ulcerogenic and TNF-α inhibitory properties.
Animals
Anti-Inflammatory Agents, Non-Steroidal
/ chemical synthesis
Anti-Ulcer Agents
/ chemical synthesis
Dose-Response Relationship, Drug
Edema
/ drug therapy
Female
Lipopolysaccharides
/ antagonists & inhibitors
Male
Mice
Mice, Inbred BALB C
Molecular Docking Simulation
Molecular Structure
Protein Kinase Inhibitors
/ chemical synthesis
Pyrazoles
/ chemical synthesis
Pyrimidines
/ chemical synthesis
Rats
Rats, Wistar
Structure-Activity Relationship
Tumor Necrosis Factor-alpha
/ antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases
/ antagonists & inhibitors
Anti-inflammatory
Docking
Pyrazolo pyrimidine
TNF-α inhibition
p38α MAP kinase
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
06
12
2018
revised:
06
03
2019
accepted:
14
03
2019
pubmed:
1
4
2019
medline:
23
9
2020
entrez:
1
4
2019
Statut:
ppublish
Résumé
A series of nine new N-substituted-4-((1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)amino)benzamides (6a-i) derivatives was synthesized. All the compounds were screened in-vitro for BSA anti-denaturation property, antioxidant assay and p38α MAP kinase inhibition. The in vitro anti-inflammatory assay results revealed that the compounds (6f-i) showed better activity than the compounds 6a-e. Compound 6f bearing the 4-chlorophenyl group showed in vitro anti-inflammatory activity (82.35 ± 4.04) comparable to standard drug diclofenac sodium (84.13 ± 1.63) and better p38α MAP kinase inhibitory activity (IC
Identifiants
pubmed: 30928877
pii: S0045-2068(18)31311-7
doi: 10.1016/j.bioorg.2019.03.037
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Anti-Ulcer Agents
0
Lipopolysaccharides
0
Protein Kinase Inhibitors
0
Pyrazoles
0
Pyrimidines
0
Tumor Necrosis Factor-alpha
0
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
550-559Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.