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 journalArticle

46 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 languageEnglish
Pages (from-to)1675-1681
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number6
DOIs
Publication statusPublished - 15-03-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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    Tan, Q., Blizzard, T. A., Morgan, J. D., Birzin, E. T., Chan, W., Yang, Y. T., Pai, L. Y., Hayes, E. C., Dasilva, C. A., Warrier, S., Yudkovitz, J., Wilkinson, H. A., Sharma, N., Fitzgerald, P. M. D., Li, S., Colwell, L., Fisher, J. E., Adamski, S., Reszka, A. A., ... 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