Abstract
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.
MeSH terms
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Adenocarcinoma
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Animals
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Anticholesteremic Agents / chemical synthesis
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Anticholesteremic Agents / chemistry
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Anticholesteremic Agents / pharmacology
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Benzopyrans / chemical synthesis*
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Benzopyrans / chemistry
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Benzopyrans / pharmacology
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Bone Density / drug effects
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Breast Neoplasms
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cholesterol / blood
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Estrogen Antagonists / chemical synthesis*
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Estrogen Antagonists / chemistry
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Estrogen Antagonists / pharmacology
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Estrogen Receptor alpha / metabolism
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Estrogen Receptor beta / metabolism
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Female
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Hot Flashes / drug therapy*
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Humans
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Morphine / pharmacology
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Naphthalenes / chemical synthesis*
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Naphthalenes / chemistry
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Naphthalenes / pharmacology
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Ovariectomy
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Rats
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Rats, Sprague-Dawley
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Selective Estrogen Receptor Modulators / chemical synthesis*
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Selective Estrogen Receptor Modulators / chemistry
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Selective Estrogen Receptor Modulators / pharmacology
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Stereoisomerism
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Uterine Neoplasms
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Uterus / drug effects
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Uterus / growth & development
Substances
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7,9-difluoro-5-(4-(2-piperidin-1-ylethoxy)phenyl)-5H-6-oxachrysen-2-ol
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Anticholesteremic Agents
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Benzopyrans
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Estrogen Antagonists
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Naphthalenes
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Selective Estrogen Receptor Modulators
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Morphine
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Cholesterol