Molecular Topology Applied to the Discovery of 1-Benzyl-2-(3-fluorophenyl)-4-hydroxy-3-(3-phenylpropanoyl)-2H-pyrrole-5-one as a Non-Ligand-Binding-Pocket Antiandrogen

被引：9

作者：

Caboni, Laura ^{[1
]}

Galvez-Llompart, Maria ^{[2
]}

Galvez, Jorge ^{[2
]}

Blanco, Fernando ^{[1
]}

Rubio-Martinez, Jaime ^{[3
,4
]}

Fayne, Darren ^{[1
]}

Lloyd, David G. ^{[1
]}

机构：

[1] Trinity Coll Dublin, Trinity Biomed Sci Inst, Sch Biochem & Immunol, Mol Design Grp, Dublin 2, Ireland

[2] Univ Valencia, Fac Pharm, Dept Phys Chem, Drug Design & Mol Connect Res Unit, Valencia, Spain

[3] Univ Barcelona, Dept Phys Chem, Barcelona, Spain

[4] Univ Barcelona, Inst Quim Teor & Computac IQTCUB, Barcelona, Spain

来源：

JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2014年 / 54卷 / 10期

关键词：

3; BF3; SITE; ANDROGEN RECEPTOR; ANTIHISTAMINIC COMPOUNDS; ACTIVE-DRUGS; PREDICTION; SEARCH; VALIDATION; CHEMISTRY; TOXICITY; PATTERN;

D O I：

10.1021/ci500324f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the discovery of 1-benzyl-2-(3-fluorophenyl)-4-hydroxy-3-(3-phenylpropanoyl)-2H-pyrrole-5-one as a novel non-ligand binding pocket (non-LBP) antagonist of the androgen receptor (AR) through the application of molecular topology techniques. This compound, validated through time-resolved fluorescence resonance energy transfer and fluorescence polarization biological assays, provides the basis for lead optimization and structureactivity relationship analysis of a new series of non-LBP AR antagonists. Induced-fit docking and molecular dynamics studies have been performed to establish a consistent hypothesis for the interaction of the new active molecule on the AR surface.

引用

页码：2953 / 2966

页数：14

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