Author/Authors :
Zhen-Qiang Tan، نويسنده , , Timothy A. Blizzard، نويسنده , , Jerry D. Morgan II، نويسنده , , Elizabeth T. Birzin، نويسنده , , Wanda Chan، نويسنده , , Yi Tien Yang، نويسنده , , Lee-Yuh Pai، نويسنده , , Edward C. Hayes، نويسنده , , Carolyn A. DaSilva، نويسنده , , Sudha Warrier، نويسنده , , Joel Yudkovitz، نويسنده , , Hilary A. Wilkinson، نويسنده , , Nandini Sharma، نويسنده , , Paula M.D. Fitzgerald، نويسنده , , Susan Li، نويسنده , , Lawrence Colwell، نويسنده , , John E. Fisher، نويسنده , , Sharon Adamski، نويسنده , , Alfred A. Reszka، نويسنده , , Donald Kimmel، نويسنده , , et al.، نويسنده ,
Abstract :
The discovery, synthesis, and SAR of chromanes as ERα subtype selective ligands are described. X-ray studies revealed that the origin of the ERα-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).
Keywords :
estrogen receptor , Subtype selectivity , Chromane , SERM , estrogen receptor antagonist , cancer , Osteoporosis , estrogen receptor alpha , SERAM
