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

 -  Bioorganic Chemistry, 32(6), p.494-503, 2004 .
<br/><br/> 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 40 position did not enhance aromatase inhibition as well as a 30-hydroxyl group. The influence of an additional 40-hydroxyl group depends on the substitution pattern of A ring. Among these molecules, 40-hydroxy-4-imidazolyl-7-methoxyflavan is only 2.2-fold less active than the letrozole (as assessed by IC50 values). Letrozole is used as the first-line therapy for metastatic breast cancer. 
<br/><br/><label>Subjects--Topical Terms: </label><br/>4-IMIDAZOLYLFLAVANS<br/>BREAST CANCER<br/>ANTI-AROMATASE EFFECT<br/>STRUCTURE-ACTIVITY RELATIONSHIPS