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Novel progesterone receptor modulators: 4-Aryl-phenylsulfonamides |
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| Authors: | Casey McComas Jeffrey Cohen Christine Huselton Michael Marella Edward Melenski Cheryl Mugford Ov Slayden Richard Winneker Jay Wrobel Matthew R. Yudt Andrew Fensome |
| Affiliation: | 1. Chemical Sciences, Drug Safety and Metabolism, Pfizer Global Research and Development, 500 Arcola Road, Collegeville, PA 19426, United States;2. Women’s Health Research Institute, Drug Safety and Metabolism, Pfizer Global Research and Development, 500 Arcola Road, Collegeville, PA 19426, United States;3. Biotransformation Division, Drug Safety and Metabolism, Pfizer Global Research and Development, 500 Arcola Road, Collegeville, PA 19426, United States;4. Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 9700, United States |
| 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. |
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