Synthesis and evaluation of 17α-E-20-(heteroaryl)norpregn-1,3,5(10),20 tetraene-3,17β-diols [17α-(heteroaryl)vinyl estradiols] as ligands for the estrogen receptor-α ligand binding domain (ERα-LBD)

被引：6

作者：

Olmsted, Sandra L. ^{[2
]}

Tongcharoensirikul, Pakamas ^{[1
]}

McCaskill, Emmett ^{[1
]}

Gandiaga, Karla ^{[1
]}

Labaree, David ^{[3
]}

Hochberg, Richard B. ^{[3
]}

Hanson, Robert N. ^{[1
]}

机构：

[1] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA

[2] Augsburg Coll, Dept Chem, Minneapolis, MN 55454 USA

[3] Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06520 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Heteroarylvinyl estradiols; Estrogen receptor-alpha ligand binding domain; Competitive binding assay; Alkaline phosphatase induction; Relative binding affinity; Relative stimulatory activity; MOLECULAR-MECHANISMS; MULTIFUNCTIONAL MEDICINES; MODULATORS; ANTIESTROGENS; SUPERFAMILY; ANTAGONISM; PROBES;

D O I：

10.1016/j.bmcl.2011.12.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 17 alpha-(heteroaryl)vinyi estradiols was prepared to evaluate the influence of heteroatom on the affinity and efficacy of estrogenic ligands for the estrogen receptor-alpha ligand binding domain (ER alpha-LBD). The products demonstrated reduced binding affinity compared to the parent 17 alpha-E-phenylvinyl estradiol, but the binding was relatively independent of the heteroatom. The greatest influence of the heteroatom was evident in the efficacy of the compounds as the thienyl derivatives 2f,g were more potent than either the pyridyl 2b-d or pyrimidinyl 2e analogs. The results suggest that a subtle interplay of interactions between the ligands and the receptor influences the biological response. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：977 / 979

页数：3

共 28 条

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Hanson, Robert N.
Olmsted, Sandra
Tongcharoensirikul, Pakamas
McCaskill, Emmett
Labaree, David C.
Hochberg, Richard B.
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2007, 234
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ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1998, 215 : U878 - U878
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ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1998, 215 : U878 - U878
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ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2004, 227 : U34 - U35
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McCaskill, E
Hochberg, RB
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ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2004, 227 : U47 - U47
[20] SYNTHESIS, RECEPTOR-BINDING, AND TISSUE DISTRIBUTION OF 7-ALPHA-SUBSTITUTED AND 11-BETA-SUBSTITUTED (17-ALPHA,20E)-21-[I-125]IODO-19-NORPREGNA-1,3,5(10),20-TETRAENE-3,17-DIOLS AND (17-ALPHA,20Z)-21-[I-125]IODO-19-NORPREGNA-1,3,5(10),20-TETRAENE-3,17-DIOLS
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