Structure-activity relationships and sub-type selectivity in an oxabicyclic estrogen receptor alpha/beta agonist scaffold.
An oxabicyclic template for estrogen receptor alpha and beta agonists has been identified which can be tuned to provide moderate levels of selectivity for either receptor sub-type. Structure-activity relationships within this phenol-substituted oxabicyclo[3.3.1]nonene series are described. Select compounds from the present series showed activity in vivo after oral dosing in rodent models of uterine proliferation.
Hamann
Lawrence G
LG
Department of Medicinal Chemistry, Ligand Pharmaceuticals, 10275 Science Centre Dr., San Diego, CA 92121, USA. lawrence.hamann@bms.com
Meyer
J Hoyt
JH
Ruppar
Daniel A
DA
Marschke
Keith B
KB
Lopez
Francisco J
FJ
Allegretto
Elizabeth A
EA
Karanewsky
Donald S
DS
D000284:Administration, Oral; D000475:Alkenes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000502:physiology; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000502:physiology; D005260:Female; D023421:Models, Animal; D008968:Molecular Conformation; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010636:Phenols / Q000737:chemistry; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014599:Uterus / Q000166:cytology / Q000187:drug effects
D000475:Alkenes; D001643:Bridged Bicyclo Compounds; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols