Synthesis and identification of novel oxa-steroids as progesterone receptor antagonists

  • Bioorg Med Chem Lett. 2007 Feb 15;17(4):907-10. doi: 10.1016/j.bmcl.2006.11.062.
Fu-An Kang  1 ,  George Allan ,  Jihua Guan ,  Nareshkumar Jain ,  Olivia Linton ,  Pamela Tannenbaum ,  Jun Xu ,  Peifang Zhu ,  Joseph Gunnet ,  Xin Chen ,  Keith Demarest ,  Scott Lundeen ,  Zhihua Sui
Affiliations
  • 1. Johnson and Johnson Pharmaceutical Research and Development, LLC, 665 Stockton Drive, Exton, PA 19341, USA. [email protected]
PMID: 17169557 DOI: 10.1016/j.bmcl.2006.11.062
Abstract

A novel series of oxa-steroids 6 derived from (8S, 13S, 14R)-7-oxa-estra-4,9-diene-3,17-dione 1 have been synthesized and identified as potent and selective Progesterone Receptor antagonists. These novel oxa-steroids showed similar potency to mifepristone. Preliminary SAR study resulted in the most potent 17-phenylethynyl oxa-steroid 6i wih an IC(50) of 1.4nM. In contrast to the equipotent mifepristone toward the Progesterone Receptor (PR) and Glucocorticoid Receptor (GR), compound 6i had over 200-fold selectivity for PR over GR.