| Literature DB >> 15745820 |
Qiang Tan1, Timothy A Blizzard, Jerry D Morgan, Elizabeth T Birzin, Wanda Chan, Yi Tien Yang, Lee-Yuh Pai, Edward C Hayes, Carolyn A DaSilva, Sudha Warrier, Joel Yudkovitz, Hilary A Wilkinson, Nandini Sharma, Paula M D Fitzgerald, Susan Li, Lawrence Colwell, John E Fisher, Sharon Adamski, Alfred A Reszka, Donald Kimmel, Frank DiNinno, Susan P Rohrer, Leonard P Freedman, James M Schaeffer, Milton L Hammond.
Abstract
The discovery, synthesis, and SAR of chromanes as ER alpha subtype selective ligands are described. X-ray studies revealed that the origin of the ER alpha-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in vivo antagonism of estradiol in an immature rat uterine weight assay, effectively inhibited ovariectomy-induced bone resorption in a 42 days treatment paradigm, and lowered serum cholesterol levels in ovx'd adult rat models. The best antagonists 8F and 12F also exhibited potent inhibition of MCF-7 cell growth and were shown to be estrogen receptor down-regulators (SERDs).Entities:
Mesh：
Substances：
Year: 2005 PMID： 15745820 DOI： 10.1016/j.bmcl.2005.01.046
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823