Synthesis and structure-activity relationship of 3-arylbenzoxazines as selective estrogen receptor beta agonists.
A series of 3-aryl-7-hydroxybenzoxazine analogues have been prepared and evaluated as ligands for the two estrogen receptor subtypes (ERalpha and ERbeta). From the radioligand binding assay, compounds with more than a 10-fold binding selectivity toward the ERbeta subtype have been identified. These compounds have also been shown to be potent full agonists in the functional assay by activation of ERE promoted transcription, with the best compound being 20-fold more potent than genistein.
Yang
Wu
W
Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. wu.yang@bms.com
Wang
Yufeng
Y
Ma
Zhengping
Z
Golla
Rajasree
R
Stouch
Terry
T
Seethala
Ramakrishna
R
Johnson
Susan
S
Zhou
Rong
R
Güngör
Timur
T
Feyen
Jean H M
JH
Dickson
John K
JK
D048588:Benzoxazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000819:agonists*; D055672:Static Electricity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D048588:Benzoxazines; D047629:Estrogen Receptor beta