Novel progesterone receptor modulators: 4-aryl-phenylsulfonamides
| Autor: | Michael Marella, Christine Huselton, Edward Melenski, Casey C. McComas, Richard C. Winneker, Cheryl Mugford, Jeffrey Cohen, Andrew Fensome, Matthew R. Yudt, Ov D. Slayden, Jay Wrobel |
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| Rok vydání: | 2012 |
| Předmět: |
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 |
| Zdroj: | Bioorganicmedicinal chemistry letters. 22(23) |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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