Issue 19, 2008
From the journal:

Organic & Biomolecular Chemistry

New scaffolds for the design of selective estrogen receptor modulators

Sonsoles Martín-Santamaría,a   José-Juan Rodríguez,a   Sonia de Pascual-Teresa,b   Sandra Gordon,c   Martin Bengtsson,c   Ignacio Garrido-Laguna,d   Belén Rubio-Viqueira,e   Pedro P. López-Casas,e   Manuel Hidalgo,d   Beatriz de Pascual-Teresa*a  and  Ana Ramos*a  

* Corresponding authors

a Departamento de Química, Facultad de Farmacia, Universidad San Pablo CEU, 28668-Boadilla del Monte, Madrid, Spain
E-mail: aramgon@ceu.es, bpaster@ceu.es
Fax: +34 913510496
Tel: +34 913724782

b Departamento de Metabolismo y Nutrición, Instituto del Frío, C.S.I.C, José Antonio Novais 10, 28040-Madrid, Spain

c Karo Bio AB, Hälsovägen, Huddinge, Sweden

d The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21230, USA

e Centro Integral Oncológico Clara Campal (CIOCC), Oña 10, 28050-Madrid, Spain

Abstract

In the present work we report the synthesis of four new ER ligands which can be used as scaffolds for the introduction of the basic side chains necessary for antiestrogenic activity. Affinities and agonist/antagonist characterization of the ligands for both ERα and ERβ have been determined in a competitive radioligand assay, and in an in vitro coactivator recruitment functional assay, respectively. Molecular modelling techniques have been used in order to rationalize the experimental results. Compound 2 is reported as a novel ERβ-agonist/ERα-antagonist. Two compounds show an interesting antitumour profile towards two pancreatic cancer cell lines and have been selected for in vivo assays.

Graphical abstract: New scaffolds for the design of selective estrogen receptor modulators

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Article information

DOI
https://doi.org/10.1039/B806918B
Article type
Paper
Submitted
24 Apr 2008
Accepted
07 Jul 2008
First published
04 Aug 2008

Org. Biomol. Chem., 2008,6, 3486-3496

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New scaffolds for the design of selective estrogen receptor modulators

S. Martín-Santamaría, J. Rodríguez, S. de Pascual-Teresa, S. Gordon, M. Bengtsson, I. Garrido-Laguna, B. Rubio-Viqueira, P. P. López-Casas, M. Hidalgo, B. de Pascual-Teresa and A. Ramos, Org. Biomol. Chem., 2008, 6, 3486 DOI: 10.1039/B806918B

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