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用于设计选择性雌激素受体调节剂的新型支架

New scaffolds for the design of selective estrogen receptor modulators.

作者信息

Martín-Santamaría Sonsoles, Rodríguez José-Juan, de Pascual-Teresa Sonia, Gordon Sandra, Bengtsson Martin, Garrido-Laguna Ignacio, Rubio-Viqueira Belén, López-Casas Pedro P, Hidalgo Manuel, de Pascual-Teresa Beatriz, Ramos Ana

机构信息

Departamento de Química, Facultad de Farmacia, Universidad San Pablo CEU, 28668-Boadilla del Monte, Madrid, Spain.

出版信息

Org Biomol Chem. 2008 Oct 7;6(19):3486-96. doi: 10.1039/b806918b. Epub 2008 Aug 4.

DOI:10.1039/b806918b
PMID:19082149
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 ERalpha and ERbeta 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 is reported as a novel ERbeta-agonist/ERalpha-antagonist. Two compounds show an interesting antitumour profile towards two pancreatic cancer cell lines and have been selected for in vivo assays.

摘要

在本研究中，我们报道了四种新型雌激素受体（ER）配体的合成，这些配体可用作引入抗雌激素活性所需碱性侧链的支架。分别通过竞争性放射性配体测定和体外共激活因子募集功能测定，确定了这些配体对雌激素受体α（ERα）和雌激素受体β（ERβ）的亲和力以及激动剂/拮抗剂特性。已使用分子建模技术来解释实验结果。化合物被报道为一种新型的雌激素受体β激动剂/雌激素受体α拮抗剂。两种化合物对两种胰腺癌细胞系显示出有趣的抗肿瘤谱，并已被选用于体内试验。

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Benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia.苯并吡喃是选择性雌激素受体β激动剂，在良性前列腺增生模型中具有新的活性。
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