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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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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cited_by cdi_FETCH-LOGICAL-c337t-dbafdd2f08067981e39fc5f25108d27b9b0a2417c482d564b63b72739f596c463
cites cdi_FETCH-LOGICAL-c337t-dbafdd2f08067981e39fc5f25108d27b9b0a2417c482d564b63b72739f596c463
container_end_page 1097
container_issue 7
container_start_page 1093
container_title Bioorganic & medicinal chemistry letters
container_volume 12
creator JACKSON, Randy W
GELINAS, Richard
BAUGHMAN, Ted A
COX, Thomas
HOWBERT, J. Jeffry
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LATHAM, John A
RAMSDELL, Fred
SINGH, Devinder
DARWISH, Ihab S
description 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.
doi_str_mv 10.1016/S0960-894X(02)00098-7
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ispartof Bioorganic & medicinal chemistry letters, 2002-04, Vol.12 (7), p.1093-1097
issn 0960-894X
1464-3405
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source Elsevier
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
title Benzobicyclooctanes as novel inhibitors of TNF-α signaling
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