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

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

Research output: Contribution to journalArticle

37 Scopus citations

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-γ) are reported. Chemical optimization of the series led to the identification of 4q (IC50 = 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.

Original languageEnglish (US)
Pages (from-to)5659-5663
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number21
DOIs
StatePublished - Nov 1 2006

Keywords

  • Alkaline phosphatase assay
  • N-Sulfonyl-2-indole carboxamides
  • Osteoporosis
  • PPAR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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    Hopkins, C. R., O'Neil, S. V., Laufersweiler, M. C., Wang, Y., Pokross, M., Mekel, M., Evdokimov, A., Walter, R., Kontoyianni, M., Petrey, M. E., Sabatakos, G., Roesgen, J. T., Richardson, E., & Demuth, T. P. (2006). Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-γ binding agents with potential application to the treatment of osteoporosis. Bioorganic and Medicinal Chemistry Letters, 16(21), 5659-5663. https://doi.org/10.1016/j.bmcl.2006.08.003