Structure-activity relationships of SERMs optimized for uterine antagonism and ovarian safety

  • Bioorg Med Chem Lett. 2007 Jul 1;17(13):3544-9. doi: 10.1016/j.bmcl.2007.04.044.
Timothy I Richardson  1 ,  Scott A Frank ,  Minmin Wang ,  Christian A Clarke ,  Scott A Jones ,  Bai-Ping Ying ,  Dan T Kohlman ,  Owen B Wallace ,  Timothy A Shepherd ,  Robert D Dally ,  Alan D Palkowitz ,  Andrew G Geiser ,  Henry U Bryant ,  Judith W Henck ,  Ilene R Cohen ,  Daniel G Rudmann ,  Denis J McCann ,  David E Coutant ,  Samuel W Oldham ,  Conrad W Hummel ,  Kin C Fong ,  Ronald Hinklin ,  George Lewis ,  Hongqi Tian ,  Jeffrey A Dodge
Affiliations
  • 1. Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. [email protected]
PMID: 17482463 DOI: 10.1016/j.bmcl.2007.04.044
Abstract

Structure-activity relationship studies are described, which led to the discovery of novel selective Estrogen Receptor modulators (SERMs) for the potential treatment of uterine fibroids. The SAR studies focused on limiting brain exposure and were guided by computational properties. Compounds with limited impact on the HPO axis were selected using serum estrogen levels as a biomarker for ovarian stimulation.