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 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 IC50 values). Letrozole is used as the first-line therapy for metastatic breast cancer.
Pouget
Christelle
C
UPRES EA 1085, Biomolécules et Cibles Cellulaires Tumorales, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 LIMOGES cedex, France.
Yahiaoui
Samir
S
Fagnere
Catherine
C
Habrioux
Gerard
G
Chulia
Albert Jose
AJ
D001141:Aromatase / Q000737:chemistry / Q000187:drug effects; D047072:Aromatase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008968:Molecular Conformation; D010920:Placenta / Q000201:enzymology; D013329:Structure-Activity Relationship
D047072:Aromatase Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D001141:Aromatase