Novel tetrahydro-β-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)

A structure–activity relationship study was conducted on a series of tetrahydro-β-carboline-1-carboxylic acid analogs against MK-2. The compounds were evaluated for their ability to inhibit TNFα production in vitro and in vivo. A structure–activity relationship study was conducted on a series of tet...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2007-08, Vol.17 (16), p.4657-4663
Main Authors: Trujillo, John I., Meyers, Marvin J., Anderson, David R., Hegde, Shridhar, Mahoney, Matthew W., Vernier, William F., Buchler, Ingrid P., Wu, Kun K., Yang, Syaluan, Hartmann, Susan J., Reitz, David B.
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - chemistry
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Carbolines - chemistry
Carbolines - pharmacology
Humans
Inflammation
MAPKAP kinase 2
Medical sciences
Mitogen-Activated Protein Kinases - antagonists & inhibitors
MK-2
Molecular Structure
Pharmacology. Drug treatments
Rats
Rheumatoid arthritis
Structure-Activity Relationship
TNF-α
U937 Cells
β-Carboline-1
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Summary:A structure–activity relationship study was conducted on a series of tetrahydro-β-carboline-1-carboxylic acid analogs against MK-2. The compounds were evaluated for their ability to inhibit TNFα production in vitro and in vivo. A structure–activity relationship study was conducted on a series of tetrahydro-β-carboline-1-carboxylic acid analogs in order to identify the key functionality responsible for activity against the mitogen-activated protein kinase-activated protein kinase 2 enzyme (MK-2). The compounds were further evaluated for their ability to inhibit TNFα production in U937 cells and in vivo. These compounds represent a novel structural class of compounds capable of inhibiting MK-2 with remarkable selectivity.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2007.05.070