Tailoring the substitution pattern of Pyrrolidine-2,5-dione for discovery of new structural template for dual COX/LOX inhibition.
Animals
Arachidonate 5-Lipoxygenase
/ metabolism
Cattle
Cyclooxygenase 2
/ metabolism
Cyclooxygenase 2 Inhibitors
/ chemical synthesis
Dose-Response Relationship, Drug
Drug Discovery
Humans
Lipoxygenase Inhibitors
/ chemical synthesis
Molecular Docking Simulation
Molecular Structure
Pyrrolidines
/ chemical synthesis
Structure-Activity Relationship
Carbonic anhydrase
Cyclooxygenases
Leukotriene
Lipoxygenase
NN-disubstituted pyrrolidine-2,5-dione
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
05
02
2021
revised:
24
04
2021
accepted:
03
05
2021
pubmed:
24
5
2021
medline:
25
2
2023
entrez:
23
5
2021
Statut:
ppublish
Résumé
Dual inhibition of the enzymatic pathways of cyclooxygenases (COX-1/COX-2) and lipoxygenase (LOX) is a rational approach for developing more efficient and safe anti-inflammatory agents. Herein, dual inhibitors of COX and LOX for the management of inflammation are reported. The structural modifications of starting pyrrolidine-2,5-dione aldehyde derivatives resulted in two structurally diverse families (Family A & B). Synthesized derivatives from both Families displayed preferential COX-2 affinity in submicromolar to nanomolar ranges. Disubstitution pattern of the most active series of compounds having N-(benzyl(4-methoxyphenyl)amino moiety presents a new template that is mimic to the diaryl pattern of traditional COX-2 inhibitors. Compound 78 with IC
Identifiants
pubmed: 34023639
pii: S0045-2068(21)00346-1
doi: 10.1016/j.bioorg.2021.104969
pii:
doi:
Substances chimiques
Cyclooxygenase 2 Inhibitors
0
Lipoxygenase Inhibitors
0
Pyrrolidines
0
pyrrolidine-2,5-dione
0
Arachidonate 5-Lipoxygenase
EC 1.13.11.34
Cyclooxygenase 2
EC 1.14.99.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104969Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.