Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-γ binding agents with potential application to the treatment of osteoporosis

The synthesis and structure–activity relationships of a novel series of N-sulfonyl-2-indole carboxamides that bind to peroxisome proliferator-activated receptor gamma (PPAR-γ) are reported. Chemical optimization of the series led to the identification of 4q (IC 50 = 50 nM) as a potent binding agent...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-11, Vol.16 (21), p.5659-5663
Main Authors: Hopkins, Corey R., O’Neil, Steven V., Laufersweiler, Michael C., Wang, Yili, Pokross, Matthew, Mekel, Marlene, Evdokimov, Artem, Walter, Richard, Kontoyianni, Maria, Petrey, Maria E., Sabatakos, Georgios, Roesgen, Jeff T., Richardson, Eloise, Demuth, Thomas P.
Format: Article
Language:English
Subjects:
3T3 Cells
Alkaline phosphatase assay
Amides - chemical synthesis
Amides - pharmacology
Animals
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Drug Design
Indoles - chemical synthesis
Indoles - pharmacology
Medical sciences
Mice
N-Sulfonyl-2-indole carboxamides
Osteoporosis
Osteoporosis - drug therapy
Pharmacology. Drug treatments
PPAR
PPAR gamma - metabolism
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Summary:The synthesis and structure–activity relationships of a novel series of N-sulfonyl-2-indole carboxamides that bind to peroxisome proliferator-activated receptor gamma (PPAR-γ) are reported. Chemical optimization of the series led to the identification of 4q (IC 50 = 50 nM) as a potent binding agent of PPAR-γ. Also reported is preliminary cell based data suggesting the use of these compounds in the treatment of osteoporosis.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.08.003