Synthesis and biological evaluation of 4-imidazolylflavans as nonsteroidal aromatase inhibitors

A series of 4-imidazolylflavans having a variety of substituents on the 2-phenyl ring was synthesized and investigated for their inhibitory effect against aromatase. Structure–activity relationships of these compounds were determined. An additional chlorine atom or a cyano group at the 4′ position d...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic chemistry 2004-12, Vol.32 (6), p.494-503
Main Authors: Pouget, Christelle, Yahiaoui, Samir, Fagnere, Catherine, Habrioux, Gerard, Chulia, Albert Jose
Format: Article
Language:English
Subjects:
4-Imidazolylflavans
Anti-aromatase effect
Aromatase - chemistry
Aromatase - drug effects
Aromatase Inhibitors - chemical synthesis
Aromatase Inhibitors - pharmacology
Breast cancer
Flavonoids - chemical synthesis
Flavonoids - pharmacology
Humans
Imidazoles - chemical synthesis
Imidazoles - pharmacology
Microsomes - drug effects
Microsomes - enzymology
Molecular Conformation
Placenta - enzymology
Structure-Activity Relationship
Structure–activity relationships
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A series of 4-imidazolylflavans having a variety of substituents on the 2-phenyl ring was synthesized and investigated for their inhibitory effect against aromatase. Structure–activity relationships of these compounds were determined. An additional chlorine atom or a cyano group at the 4′ position did not enhance aromatase inhibition as well as a 3′-hydroxyl group. The influence of an additional 4′-hydroxyl group depends on the substitution pattern of A ring. Among these molecules, 4′-hydroxy-4-imidazolyl-7-methoxyflavan is only 2.2-fold less active than the letrozole (as assessed by IC 50 values). Letrozole is used as the first-line therapy for metastatic breast cancer.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2004.06.008