TY - JOUR
T1 - Estrogen receptor ligands. Part 10
T2 - Chromanes: Old scaffolds for new SERAMs
AU - Tan, Qiang
AU - Blizzard, Timothy A.
AU - Morgan, Jerry D.
AU - Birzin, Elizabeth T.
AU - Chan, Wanda
AU - Yang, Yi Tien
AU - Pai, Lee Yuh
AU - Hayes, Edward C.
AU - Dasilva, Carolyn A.
AU - Warrier, Sudha
AU - Yudkovitz, Joel
AU - Wilkinson, Hilary A.
AU - Sharma, Nandini
AU - Fitzgerald, Paula M.D.
AU - Li, Susan
AU - Colwell, Lawrence
AU - Fisher, John E.
AU - Adamski, Sharon
AU - Reszka, Alfred A.
AU - Kimmel, Donald
AU - Dininno, Frank
AU - Rohrer, Susan P.
AU - Freedman, Leonard P.
AU - Schaeffer, James M.
AU - Hammond, Milton L.
PY - 2005/3/15
Y1 - 2005/3/15
N2 - 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).
AB - 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).
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U2 - 10.1016/j.bmcl.2005.01.046
DO - 10.1016/j.bmcl.2005.01.046
M3 - Article
C2 - 15745820
AN - SCOPUS:20044395599
SN - 0960-894X
VL - 15
SP - 1675
EP - 1681
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 6
ER -