Novel progesterone receptor modulators: 4-aryl-phenylsulfonamides

  • Bioorg Med Chem Lett. 2012 Dec 1;22(23):7119-22. doi: 10.1016/j.bmcl.2012.09.077.
Casey McComas  1 ,  Jeffrey Cohen ,  Christine Huselton ,  Michael Marella ,  Edward Melenski ,  Cheryl Mugford ,  Ov Slayden ,  Richard Winneker ,  Jay Wrobel ,  Matthew R Yudt ,  Andrew Fensome
Affiliations
  • 1. Chemical Sciences, Drug Safety and Metabolism, Pfizer Global Research and Development, 500 Arcola Road, Collegeville, PA 19426, USA.
PMID: 23079530 DOI: 10.1016/j.bmcl.2012.09.077
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.