1. Novel progesterone receptor modulators: 4-aryl-phenylsulfonamides
- Author
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Michael Marella, Christine Huselton, Edward Melenski, Casey C. McComas, Richard C. Winneker, Cheryl Mugford, Jeffrey Cohen, Andrew Fensome, Matthew R. Yudt, Ov D. Slayden, and Jay Wrobel
- Subjects
Male ,Clinical Biochemistry ,Pharmaceutical Science ,Administration, Oral ,Progesterone receptor modulators ,Pharmacology ,Biochemistry ,Progesterone Antagonist ,Ames test ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Progesterone receptor ,Animals ,Humans ,Molecular Biology ,Sulfonamides ,Chemistry ,Aryl ,Organic Chemistry ,Alkaline Phosphatase ,Macaca mulatta ,Rats ,Molecular Medicine ,Receptors, Progesterone ,Half-Life - 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.
- Published
- 2012