Design and synthesis of tamoxifen derivatives as a selective estrogen receptor down-regulator

Takuji Shoda; Keiichiro Okuhira; Masashi Kato; Yosuke Demizu; Hideshi Inoue; Mikihiko Naito; Masaaki Kurihara

doi:10.1016/j.bmcl.2013.11.078

Design and synthesis of tamoxifen derivatives as a selective estrogen receptor down-regulator

Bioorg Med Chem Lett. 2014 Jan 1;24(1):87-9. doi: 10.1016/j.bmcl.2013.11.078. Epub 2013 Dec 4.

Authors

Takuji Shoda¹, Keiichiro Okuhira², Masashi Kato³, Yosuke Demizu⁴, Hideshi Inoue⁵, Mikihiko Naito², Masaaki Kurihara⁶

Affiliations

¹ Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. Electronic address: tsho@nihs.go.jp.
² Division of Biochemistry and Molecular Biology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
³ Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
⁴ Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
⁵ School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
⁶ Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, Kanagawa 226-8501, Japan. Electronic address: masaaki@nihs.go.jp.

PMID: 24332630
DOI: 10.1016/j.bmcl.2013.11.078

Abstract

We designed and synthesized an estrogen receptor (ER) down-regulator (5), which is a derivative of tamoxifen with a long alkyl side chain. Compound 5 effectively reduced ER protein levels in MCF-7 cells and had an antagonistic effect.

Keywords: Breast cancer; Estrogen receptor; SERD; Tamoxifen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Down-Regulation / drug effects
Drug Design*
Humans
MCF-7 Cells
Molecular Structure
Receptors, Estrogen / antagonists & inhibitors*
Structure-Activity Relationship
Tamoxifen / chemical synthesis
Tamoxifen / chemistry
Tamoxifen / pharmacology*

Substances

Receptors, Estrogen
Tamoxifen