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Synthesis and structure-activity relationship studies of novel dihydropyridones as androgen receptor modulators.

Abstract：

:A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeling and molecular mechanics were used to build a structural model of the androgen receptor-ligand binding domain and to investigate the structural basis of the antagonism. The model is qualitatively consistent with the observed SAR. Moreover, the enrichment plot shows that screening with the model performs significantly better than random screening. Therefore, the model probably represents a realistic conformation of the antagonist form and can be utilized for structure-based design of novel antiandrogens.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Pepe A,Pamment M,Kim YS,Lee S,Lee MJ,Beebe K,Filikov A,Neckers L,Trepel JB,Malhotra SV

doi

10.1021/jm301714s

subject

Has Abstract

pub_date

2013-11-14 00:00:00

pages

8280-97

issue

21

eissn

0022-2623

issn

1520-4804

journal_volume

56

pub_type

杂志文章

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