Estrogen receptor ligands. Part 10: Chromanes: Old scaffolds for new SERAMs

Qiang Tan; 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

doi:10.1016/j.bmcl.2005.01.046

Estrogen receptor ligands. Part 10: Chromanes: Old scaffolds for new SERAMs

Qiang Tan, 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 KimmelFrank Dininno, Susan P. Rohrer, Leonard P. Freedman, James M. Schaeffer, Milton L. Hammond

Research output: Contribution to journal › Article

45 Citations (Scopus)

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	https://doi.org/10.1016/j.bmcl.2005.01.046
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

Tan, Q., Blizzard, T. A., Morgan, J. D., Birzin, E. T., Chan, W., Yang, Y. T., ... Hammond, M. L. (2005). Estrogen receptor ligands. Part 10: Chromanes: Old scaffolds for new SERAMs. Bioorganic and Medicinal Chemistry Letters, 15(6), 1675-1681. https://doi.org/10.1016/j.bmcl.2005.01.046

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. / Estrogen receptor ligands. Part 10 : Chromanes: Old scaffolds for new SERAMs. In: Bioorganic and Medicinal Chemistry Letters. 2005 ; Vol. 15, No. 6. pp. 1675-1681.

@article{692674d9db034a1da759da37db8b7105,

title = "Estrogen receptor ligands. Part 10: Chromanes: Old scaffolds for new SERAMs",

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).",

author = "Qiang Tan and Blizzard, {Timothy A.} and Morgan, {Jerry D.} and Birzin, {Elizabeth T.} and Wanda Chan and Yang, {Yi Tien} and Pai, {Lee Yuh} and Hayes, {Edward C.} and Dasilva, {Carolyn A.} and Sudha Warrier and Joel Yudkovitz and Wilkinson, {Hilary A.} and Nandini Sharma and Fitzgerald, {Paula M.D.} and Susan Li and Lawrence Colwell and Fisher, {John E.} and Sharon Adamski and Reszka, {Alfred A.} and Donald Kimmel and Frank Dininno and Rohrer, {Susan P.} and Freedman, {Leonard P.} and Schaeffer, {James M.} and Hammond, {Milton L.}",

year = "2005",

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Tan, Q, Blizzard, TA, Morgan, JD, Birzin, ET, Chan, W, Yang, YT, Pai, LY, Hayes, EC, Dasilva, CA, Warrier, S, Yudkovitz, J, Wilkinson, HA, Sharma, N, Fitzgerald, PMD, Li, S, Colwell, L, Fisher, JE, Adamski, S, Reszka, AA, Kimmel, D, Dininno, F, Rohrer, SP, Freedman, LP, Schaeffer, JM & Hammond, ML 2005, 'Estrogen receptor ligands. Part 10: Chromanes: Old scaffolds for new SERAMs', Bioorganic and Medicinal Chemistry Letters, vol. 15, no. 6, pp. 1675-1681. https://doi.org/10.1016/j.bmcl.2005.01.046

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).

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DO - 10.1016/j.bmcl.2005.01.046

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AN - SCOPUS:20044395599

VL - 15

SP - 1675

EP - 1681

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

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Access to Document

10.1016/j.bmcl.2005.01.046