Novel progesterone receptor modulators: 4-Aryl-phenylsulfonamides

Casey McComas, Jeffrey Cohen, Christine Huselton, Michael Marella, Edward Melenski, Cheryl Mugford, Ov Slayden, Richard Winneker, Jay Wrobel, Matthew R. Yudt, Andrew Fensome

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    We have developed a new series of progesterone receptor modulators based upon the 4-aryl-phenylsulfonamide. Initial work in the series afforded potent compounds with good properties, however an advanced intermediate proved to be genotoxic in a non-GLP Ames assay following metabolic activation. We subsequently solved this problem and identified advanced leads which demonstrated oral efficacy in rhesus monkey pharmacodynamic and kinetics models.

    Original languageEnglish (US)
    Pages (from-to)7119-7122
    Number of pages4
    JournalBioorganic and Medicinal Chemistry Letters
    Volume22
    Issue number23
    DOIs
    StatePublished - Dec 1 2012

    Fingerprint

    Pharmacodynamics
    Progesterone Receptors
    Macaca mulatta
    Modulators
    Assays
    Chemical activation
    Kinetics
    Metabolic Activation

    Keywords

    • Endometriosis
    • Progesterone antagonist
    • Progesterone modulator
    • Uterine fibroids

    ASJC Scopus subject areas

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

    Cite this

    McComas, C., Cohen, J., Huselton, C., Marella, M., Melenski, E., Mugford, C., ... Fensome, A. (2012). Novel progesterone receptor modulators: 4-Aryl-phenylsulfonamides. Bioorganic and Medicinal Chemistry Letters, 22(23), 7119-7122. https://doi.org/10.1016/j.bmcl.2012.09.077

    Novel progesterone receptor modulators : 4-Aryl-phenylsulfonamides. / McComas, Casey; Cohen, Jeffrey; Huselton, Christine; Marella, Michael; Melenski, Edward; Mugford, Cheryl; Slayden, Ov; Winneker, Richard; Wrobel, Jay; Yudt, Matthew R.; Fensome, Andrew.

    In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 23, 01.12.2012, p. 7119-7122.

    Research output: Contribution to journalArticle

    McComas, C, Cohen, J, Huselton, C, Marella, M, Melenski, E, Mugford, C, Slayden, O, Winneker, R, Wrobel, J, Yudt, MR & Fensome, A 2012, 'Novel progesterone receptor modulators: 4-Aryl-phenylsulfonamides', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 23, pp. 7119-7122. https://doi.org/10.1016/j.bmcl.2012.09.077
    McComas C, Cohen J, Huselton C, Marella M, Melenski E, Mugford C et al. Novel progesterone receptor modulators: 4-Aryl-phenylsulfonamides. Bioorganic and Medicinal Chemistry Letters. 2012 Dec 1;22(23):7119-7122. https://doi.org/10.1016/j.bmcl.2012.09.077
    McComas, Casey ; Cohen, Jeffrey ; Huselton, Christine ; Marella, Michael ; Melenski, Edward ; Mugford, Cheryl ; Slayden, Ov ; Winneker, Richard ; Wrobel, Jay ; Yudt, Matthew R. ; Fensome, Andrew. / Novel progesterone receptor modulators : 4-Aryl-phenylsulfonamides. In: Bioorganic and Medicinal Chemistry Letters. 2012 ; Vol. 22, No. 23. pp. 7119-7122.
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