Estrogen receptor ligands: design and synthesis of new 2-arylindene-1-ones.
The syntheses of a series of 2-arylindene-1-ones as potent ligands of ERbeta and ERalpha are described. Several compounds exhibited high potency and moderate selectivity for the ERbeta receptor. X-ray and modeling studies were used to understand ligand binding orientation and observed affinity.
McDevitt
Robert E
RE
Department of Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA. mcdevib@wyeth.com
Malamas
Michael S
MS
Manas
Eric S
ES
Unwalla
Rayomand J
RJ
Xu
Zhang B
ZB
Miller
Chris P
CP
Harris
Heather A
HA
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015195:Drug Design; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D019833:Genistein / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D011869:Radioligand Assay; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
C413384:1,2-indanedione; D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007189:Indans; D008024:Ligands; D019833:Genistein