2-Amino-4,6-diarylpyridines as novel ligands for the estrogen receptor.
We have prepared a novel series of 2-amino-4,6-diarylpyridines that function as ligands of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta). These compounds bind to both ERalpha and ERbeta with a modest selectivity for the alpha subtype. The most potent of these analogues, compound 19, has a K(i)=20nM at ERalpha. These molecules represent a novel template for designing potentially useful ligands for the estrogen receptor.
Henke
B R
BR
Department of Medicinal Chemistry, Glaxo Wellcome Research and Development, Five Moore Drive, 27709, Research Triangle Park, NC, USA. brh14990@gsk.com
Drewry
D H
DH
Jones
S A
SA
Stewart
E L
EL
Weaver
S L
SL
Wiethe
R W
RW
D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D018360:Crystallography, X-Ray; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006801:Humans; D008024:Ligands; D011485:Protein Binding / Q000502:physiology; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000494:pharmacology*; D012680:Sensitivity and Specificity
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D011725:Pyridines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride