ERbeta ligands. Part 4: Synthesis and structure-activity relationships of a series of 2-phenylquinoline derivatives.
A new class of estrogen receptor beta (ERbeta) ligands based on the 2-phenylquinoline scaffold was prepared. Several analogues with C4 substitution displayed high affinity (3-5 nM) and significant selectivity (up to 83-fold) for ERbeta. The best compound, 13b, was profiled as a selective partial agonist for ERbeta at 1 muM in a cell-based transcriptional assay. Uterine weight bioassay of 13b indicated no activation of ERalpha in vivo.
Vu
An T
AT
Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. vua@wyeth.com
Cohn
Stephen T
ST
Manas
Eric S
ES
Harris
Heather A
HA
Mewshaw
Richard E
RE
D016227:Benzoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D008958:Models, Molecular; D011869:Radioligand Assay; D013329:Structure-Activity Relationship
D016227:Benzoquinones; D047629:Estrogen Receptor beta; C029322:phenylbenzoquinone