title: Lead optimization providing a series of flavone derivatives as potent nonsteroidal inhibitors of the cytochrome P450 aromatase enzyme.
abstract: Following our SAR studies on aromatase inhibitors, new compounds were designed by appropriately modifying the structure of flavone 1 using our previously reported CoMFA model. While the introduction of substituents on the 2-phenyl ring alone did not cause improvement in potency, these modifications and the removal of the 7-methoxy group led to compounds showing inhibitory activity in the nanomolar range, comparable to the marketed drug fadrozole.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro, 6, I-40126 Bologna, Italy. silvia.gobbi@unibo.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Gobbi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Angela
authors.initials: A
authors.lastname: Rampa
authors.forename: Federica
authors.initials: F
authors.lastname: Belluti
authors.forename: Lorna
authors.initials: L
authors.lastname: Piazzi
authors.forename: Anja
authors.initials: A
authors.lastname: Paluszcak
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisi
mesh_terms: D001141:Aromatase / Q000737:chemistry*; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D017316:Fadrozole / Q000737:chemistry; D047309:Flavones / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D047072:Aromatase Inhibitors; D047309:Flavones; D001141:Aromatase; D017316:Fadrozole