Design, Synthesis, and Biological Evaluation of a Series of Oxazolone Carboxamides as a Novel Class of Acid Ceramidase Inhibitors.
Acid Ceramidase
/ antagonists & inhibitors
Administration, Oral
Animals
Binding Sites
Cell Line, Tumor
Drug Design
Enzyme Inhibitors
/ chemical synthesis
Half-Life
Humans
Inhibitory Concentration 50
Kinetics
Male
Mice
Mice, Inbred C57BL
Microsomes
/ metabolism
Molecular Docking Simulation
Oxazolone
/ chemistry
Solubility
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:
24 12 2020
24 12 2020
Historique:
pubmed:
9
12
2020
medline:
3
2
2021
entrez:
8
12
2020
Statut:
ppublish
Résumé
Acid ceramidase (AC) is a cysteine hydrolase that plays a crucial role in the metabolism of lysosomal ceramides, important members of the sphingolipid family, a diversified class of bioactive molecules that mediate many biological processes ranging from cell structural integrity, signaling, and cell proliferation to cell death. In the effort to expand the structural diversity of the existing collection of AC inhibitors, a novel class of substituted oxazol-2-one-3-carboxamides were designed and synthesized. Herein, we present the chemical optimization of our initial hits, 2-oxo-4-phenyl-
Identifiants
pubmed: 33290061
doi: 10.1021/acs.jmedchem.0c01561
pmc: PMC7770833
doi:
Substances chimiques
Enzyme Inhibitors
0
Oxazolone
15646-46-5
Acid Ceramidase
EC 3.5.1.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15821-15851Références
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