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).
| Original language | English |
|---|---|
| Pages (from-to) | 1675-1681 |
| Number of pages | 7 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 15 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 15-03-2005 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Cite this
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Estrogen receptor ligands. Part 10 : Chromanes: Old scaffolds for new SERAMs. / Tan, Qiang; Blizzard, Timothy A.; Morgan, Jerry D.; Birzin, Elizabeth T.; Chan, Wanda; Yang, Yi Tien; Pai, Lee Yuh; Hayes, Edward C.; Dasilva, Carolyn A.; Warrier, Sudha; Yudkovitz, Joel; Wilkinson, Hilary A.; Sharma, Nandini; Fitzgerald, Paula M.D.; Li, Susan; Colwell, Lawrence; Fisher, John E.; Adamski, Sharon; Reszka, Alfred A.; Kimmel, Donald; Dininno, Frank; Rohrer, Susan P.; Freedman, Leonard P.; Schaeffer, James M.; Hammond, Milton L.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 15, No. 6, 15.03.2005, p. 1675-1681.Research output: Contribution to journal › Article
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).
UR - http://www.scopus.com/inward/record.url?scp=20044395599&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20044395599&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2005.01.046
DO - 10.1016/j.bmcl.2005.01.046
M3 - Article
C2 - 15745820
AN - SCOPUS:20044395599
VL - 15
SP - 1675
EP - 1681
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 6
ER -