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

doi:10.1016/j.bmcl.2006.08.003

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 journal › Article › peer-review

47 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 language	English (US)
Pages (from-to)	5659-5663
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2006.08.003
State	Published - Nov 1 2006
Externally published	Yes

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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10.1016/j.bmcl.2006.08.003

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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

Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-γ binding agents with potential application to the treatment of osteoporosis. / Hopkins, Corey R.; O'Neil, Steven V.; Laufersweiler, Michael C. et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 21, 01.11.2006, p. 5659-5663.

Research output: Contribution to journal › Article › peer-review

Hopkins, CR, O'Neil, SV, Laufersweiler, MC, Wang, Y, Pokross, M, Mekel, M, Evdokimov, A, Walter, R, Kontoyianni, M, Petrey, ME, Sabatakos, G, Roesgen, JT, Richardson, E & Demuth, TP 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, vol. 16, no. 21, pp. 5659-5663. https://doi.org/10.1016/j.bmcl.2006.08.003

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title = "Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-γ 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-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.",

keywords = "Alkaline phosphatase assay, N-Sulfonyl-2-indole carboxamides, Osteoporosis, PPAR",

author = "Hopkins, {Corey R.} and O'Neil, {Steven V.} and Laufersweiler, {Michael C.} and Yili Wang and Matthew Pokross and Marlene Mekel and Artem Evdokimov and Richard Walter and Maria Kontoyianni and Petrey, {Maria E.} and Georgios Sabatakos and Roesgen, {Jeff T.} and Eloise Richardson and Demuth, {Thomas P.}",

note = "Funding Information: 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. ",

year = "2006",

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doi = "10.1016/j.bmcl.2006.08.003",

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AU - Hopkins, Corey R.

AU - O'Neil, Steven V.

AU - Laufersweiler, Michael C.

AU - Wang, Yili

AU - Pokross, Matthew

AU - Mekel, Marlene

AU - Evdokimov, Artem

AU - Walter, Richard

AU - Kontoyianni, Maria

AU - Petrey, Maria E.

AU - Sabatakos, Georgios

AU - Roesgen, Jeff T.

AU - Richardson, Eloise

AU - Demuth, Thomas P.

N1 - Funding Information: 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.

PY - 2006/11/1

Y1 - 2006/11/1

N2 - 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.

AB - 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.

KW - Alkaline phosphatase assay

KW - N-Sulfonyl-2-indole carboxamides

KW - Osteoporosis

KW - PPAR

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

Abstract

Keywords

ASJC Scopus subject areas

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