Synthesis of 3-alkyl naphthalenes as novel estrogen receptor ligands.
A series of estrogen receptor ligands based on a 3-alkyl naphthalene scaffold was synthesized using an intramolecular enolate-alkyne cycloaromatization as the key step. Several of these compounds bearing a C6-OH group were shown to be high affinity ligands. All compounds had similar ERalpha and ERbeta binding affinity ranging from micromolar to low nanomolar.
Fang
Jing
J
GlaxoSmithKline Research, 5 Moore Drive, Research Triangle Park, NC 27709, USA. jing.m.fang@gsk.com
Akwabi-Ameyaw
Adwoa
A
Britton
Jonathan E
JE
Katamreddy
Subba R
SR
Navas
Frank
F
Miller
Aaron B
AB
Williams
Shawn P
SP
Gray
David W
DW
Orband-Miller
Lisa A
LA
Shearin
Jean
J
Heyer
Dennis
D
D020650:Combinatorial Chemistry Techniques; D020847:Estrogen Receptor Modulators / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000819:agonists*; D020845:Selective Estrogen Receptor Modulators / Q000378:metabolism; D013329:Structure-Activity Relationship
D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D009281:Naphthalenes; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators