Benzobicyclooctanes as novel inhibitors of TNF-α signaling

A novel series of TNF-alpha inhibitors based on a benzobicyclooctane scaffold is reported. The compounds display good potency in inhibiting TNF-alpha induced apoptosis and NF kappa B activation. Additionally, they are selective for TNF-alpha as they do not inhibit apoptosis induced by soluble Fas li...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2002-04, Vol.12 (7), p.1093-1097
Main Authors: JACKSON, Randy W, GELINAS, Richard, BAUGHMAN, Ted A, COX, Thomas, HOWBERT, J. Jeffry, KUCERA, Kristin A, LATHAM, John A, RAMSDELL, Fred, SINGH, Devinder, DARWISH, Ihab S
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Apoptosis - physiology
Biological and medical sciences
Fas Ligand Protein
Humans
Immunomodulators
Lung Neoplasms - drug therapy
Medical sciences
Membrane Glycoproteins - pharmacology
Molecular Structure
NF-kappa B - drug effects
NF-kappa B - metabolism
Octanes - pharmacology
Pharmacology. Drug treatments
Signal Transduction - physiology
Tumor Cells, Cultured - drug effects
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Tumor Necrosis Factor-alpha - metabolism
Tumor Necrosis Factor-alpha - pharmacology
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Summary:A novel series of TNF-alpha inhibitors based on a benzobicyclooctane scaffold is reported. The compounds display good potency in inhibiting TNF-alpha induced apoptosis and NF kappa B activation. Additionally, they are selective for TNF-alpha as they do not inhibit apoptosis induced by soluble Fas ligand. The compounds described here can act as leads for future medicinal chemistry efforts and may also be useful tools for elucidating the TNF-alpha signaling pathway.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(02)00098-7