title: Lead optimization of 4-imidazolylflavans: new promising aromatase inhibitors.
abstract: Our previous studies have shown that several 7-substituted-4-imidazolylflavans are potent inhibitors of aromatase. These compounds were designed considering the anti-aromatase effect of some natural flavonoids and the importance of an azole ring for synthetic inhibitors such as letrozole or anastrozole towards binding to the heme iron of aromatase. In this study, we report the optimization of these lead compounds by the modulation of flavan A ring. The resulting 7,8-benzo-4-imidazolylflavans were tested in order to assess their ability to inhibit aromatase. Biological data concerning enantiomers obtained from the chiral separation of the racemate compound 4-imidazolyl-7-methoxyflavan are also presented.
authors.affiliation: UPRES EA 4021 Biomolécules et Thérapies anti-tumorales, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges cedex, France. samir.yahiaoui@unilim.fr
authors.forename: Samir
authors.initials: S
authors.lastname: Yahiaoui
authors.forename: Christelle
authors.initials: C
authors.lastname: Pouget
authors.forename: Jacques
authors.initials: J
authors.lastname: Buxeraud
authors.forename: Albert José
authors.initials: AJ
authors.lastname: Chulia
authors.forename: Catherine
authors.initials: C
authors.lastname: Fagnère
mesh_terms: D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D047072:Aromatase Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D001141:Aromatase