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

Abstract

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-gamma) are reported. Chemical optimization of the series led to the identification of 4q (IC(50)=50 nM) as a potent binding agent of PPAR-gamma. Also reported is preliminary cell based data suggesting the use of these compounds in the treatment of osteoporosis.

• Authors: Corey R Hopkins, Steven V O'neil, Michael C Laufersweiler, Yili Wang, Matthew Pokross, Marlene Mekel, Artem Evdokimov, Richard Walter, Maria Kontoyianni, Maria E Petrey, Georgios Sabatakos, Jeff T Roesgen, Eloise Richardson, Thomas P Demuth Jr
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 16 Issue 21 Pg. 5659-63 (Nov 01 2006) ISSN: 0960-894X [Print] England
• PMID: 16919947 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Amides
• Indoles
• PPAR gamma

Topics

• 3T3 Cells
• Amides (chemical synthesis, pharmacology)
• Animals
• Drug Design
• Indoles (chemical synthesis, pharmacology)
• Mice
• Osteoporosis (drug therapy)
• PPAR gamma (metabolism)