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

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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.

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Acknowledgments

X-ray data were collected at SER-CAT 22-ID beam line at the Advanced Photon Source, Argonne National Laboratory. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. All relevant structures were submitted to the PDB, code 2HFP.

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