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

• 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
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2004.06.008

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.