A selective estrogen receptor modulator for the treatment of hot flushes.
A selective estrogen receptor modulator (SERM) for the potential treatment of hot flushes is described. (R)-(+)-7,9-difluoro-5-[4-(2-piperidin-1-ylethoxy)phenyl]-5H-6-oxachrysen-2-ol, LSN2120310, potently binds ERalpha and ERbeta and is an antagonist in MCF-7 breast adenocarcinoma and Ishikawa uterine cancer cell lines. The compound is a potent estrogen antagonist in the rat uterus. In ovariectomized rats, the compound lowers cholesterol, maintains bone mineral density, and is efficacious in a morphine dependent rat model of hot flush efficacy.
Wallace
Owen B
OB
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. owen.wallace@lilly.com
Lauwers
Kenneth S
KS
Dodge
Jeffrey A
JA
May
Scott A
SA
Calvin
Joel R
JR
Hinklin
Ronald
R
Bryant
Henry U
HU
Shetler
Pamela K
PK
Adrian
Mary D
MD
Geiser
Andrew G
AG
Sato
Masahiko
M
Burris
Thomas P
TP
D000230:Adenocarcinoma; D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004965:Estrogen Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D009020:Morphine / Q000494:pharmacology; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D014594:Uterine Neoplasms; D014599:Uterus / Q000187:drug effects / Q000254:growth & development
C508986:7,9-difluoro-5-(4-(2-piperidin-1-ylethoxy)phenyl)-5H-6-oxachrysen-2-ol; D000924:Anticholesteremic Agents; D001578:Benzopyrans; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009281:Naphthalenes; D020845:Selective Estrogen Receptor Modulators; D009020:Morphine; D002784:Cholesterol