New antiestrogens from a library screen of homoallylic amides, allylic amides, and C-cyclopropylalkylamides

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

13 Scopus Citations
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Author(s)

  • Jelena M. Janjic
  • Ying Mu
  • Christopher Kendall
  • Corey R.J. Stephenson
  • Raghavan Balachandran
  • Brianne S. Raccor
  • Ying Lu
  • Wen Xie
  • Peter Wipf
  • Billy W. Day

Detail(s)

Original languageEnglish
Pages (from-to)157-164
Journal / PublicationBioorganic and Medicinal Chemistry
Volume13
Issue number1
Publication statusPublished - 3 Jan 2005
Externally publishedYes

Abstract

A new structural scaffold for antiestrogens was identified from the cell-based screening of a 67-member library of homoallylic amides, allylic amides, and C-cyclopropylalkylamides. Several derivatives had activity comparable to that of tamoxifen. A new structural scaffold for antiestrogens was identified from the cell-based screening of transcriptional regulation properties of a 67-member library of homoallylic amides, allylic amides, and C-cyclopropylalkylamides. C-Cyclopropylalkylamide 3a (O-ethyl-N-{2-[(1S*, 2R*)-2-{(R*)-[(diphenylphosphinoyl)amino](phenyl)methyl}cyclopropyl] ethyl}-N-[(4-methylphenyl)sulfonyl]carbamate) had antagonistic activity similar to that of tamoxifen and was further evaluated. Compound 3a inhibited estradiol-induced proliferation of the ER-positive MCF-7 cells but had no effect on ER-negative MDA-MB231 human breast cancer cells. Furthermore, high micromolar concentrations of 3a exhibited minimal cytotoxicity to the ER-negative line. The biological activities of the enantiomers of 3a did not differ from one another nor from that of racemic 3a. © 2004 Elsevier Ltd. All rights reserved.

Research Area(s)

  • Cell-based screen, Estrogen receptor α, Estrogen response element, Fluorescent estrogen, Transcription

Citation Format(s)

New antiestrogens from a library screen of homoallylic amides, allylic amides, and C-cyclopropylalkylamides. / Janjic, Jelena M.; Mu, Ying; Kendall, Christopher; Stephenson, Corey R.J.; Balachandran, Raghavan; Raccor, Brianne S.; Lu, Ying; Zhu, Guangyu; Xie, Wen; Wipf, Peter; Day, Billy W.

In: Bioorganic and Medicinal Chemistry, Vol. 13, No. 1, 03.01.2005, p. 157-164.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal