Benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia

  • J Med Chem. 2006 Oct 19;49(21):6155-7. doi: 10.1021/jm060491j.
Bryan H Norman  1 ,  Jeffrey A Dodge ,  Timothy I Richardson ,  Peter S Borromeo ,  Charles W Lugar ,  Scott A Jones ,  Keyue Chen ,  Yong Wang ,  Gregory L Durst ,  Robert J Barr ,  Chahrzad Montrose-Rafizadeh ,  Harold E Osborne ,  Robert M Amos ,  Sherry Guo ,  Amechand Boodhoo ,  Venkatesh Krishnan
Affiliations
  • 1. Discovery Chemistry Research, Bone and Inflammation Research, Lead Optimization Biology, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. [email protected]
PMID: 17034120 DOI: 10.1021/jm060491j
Abstract

Benzopyran selective Estrogen receptor beta agonist-1 (SERBA-1) shows potent, selective binding and agonist function in Estrogen receptor beta (ERbeta) in vitro assays. X-ray crystal structures of SERBA-1 in ERalpha and beta help explain observed beta-selectivity of this ligand. SERBA-1 in vivo demonstrates involution of the ventral prostate in CD-1 mice (ERbeta effect), while having no effect on gonadal hormone levels (ERalpha effect) at 10x the efficacious dose, consistent with in vitro properties of this molecule.