Lead optimization providing a series of flavone derivatives as potent nonsteroidal inhibitors of the cytochrome P450 aromatase enzyme.
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.
Gobbi
Silvia
S
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro, 6, I-40126 Bologna, Italy. silvia.gobbi@unibo.it
Cavalli
Andrea
A
Rampa
Angela
A
Belluti
Federica
F
Piazzi
Lorna
L
Paluszcak
Anja
A
Hartmann
Rolf W
RW
Recanatini
Maurizio
M
Bisi
Alessandra
A
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
D047072:Aromatase Inhibitors; D047309:Flavones; D001141:Aromatase; D017316:Fadrozole