7-Substituted 2-phenyl-benzofurans as ER beta selective ligands.
A series of 2-(4-hydroxy-phenyl)-benzofuran-5-ols with relatively lipophilic groups in the 7-position of the benzofuran was prepared and the affinity and selectivity for ER beta was measured. Many of the analogues were found to be potent and selective ER beta ligands. Additional modifications at the benzofuran 4-position as well as at the 3'-position of the 2-phenyl group were found to further increase selectivity. Such modifications led to compounds with <10 nM potency and >100-fold selectivity for ER beta.
Collini
Michael D
MD
Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. collinm2@wyeth.com
Kaufman
David H
DH
Manas
Eric S
ES
Harris
Heather A
HA
Henderson
Ruth A
RA
Xu
Zhang B
ZB
Unwalla
Rayomand J
RJ
Miller
Chris P
CP
D001572:Benzofurans / Q000138:chemical synthesis* / Q000378:metabolism; D045744:Cell Line, Tumor; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics; D008024:Ligands; D012333:RNA, Messenger / Q000032:analysis; D013329:Structure-Activity Relationship
D001572:Benzofurans; D047629:Estrogen Receptor beta; D018974:Insulin-Like Growth Factor Binding Protein 4; D008024:Ligands; D012333:RNA, Messenger