A Selective Estrogen Receptor Modulator for the Treatment of Hot Flushes

• Published in: Journal of medicinal chemistry Vol. 49; no. 3; pp. 843 - 846
• Main Authors: Wallace, Owen B, Lauwers, Kenneth S, Dodge, Jeffrey A, May, Scott A, Calvin, Joel R, Hinklin, Ronald, Bryant, Henry U, Shetler, Pamela K, Adrian, Mary D, Geiser, Andrew G, Sato, Masahiko, Burris, Thomas P
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 09.02.2006; Amer Chemical Soc
• Subjects: Adenocarcinoma; Animals; Anticholesteremic Agents - chemical synthesis; Anticholesteremic Agents - chemistry; Anticholesteremic Agents - pharmacology; Benzopyrans - chemical synthesis; Benzopyrans - chemistry; Benzopyrans - pharmacology; Biological and medical sciences; Bone Density - drug effects; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry, Medicinal; Cholesterol - blood; Estrogen Antagonists - chemical synthesis; Estrogen Antagonists - chemistry; Estrogen Antagonists - pharmacology; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - metabolism; Female; Hormones. Endocrine system; Hot Flashes - drug therapy; Humans; Life Sciences & Biomedicine; Medical sciences; Morphine - pharmacology; Naphthalenes - chemical synthesis; Naphthalenes - chemistry; Naphthalenes - pharmacology; Ovariectomy; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Science & Technology; Selective Estrogen Receptor Modulators - chemical synthesis; Selective Estrogen Receptor Modulators - chemistry; Selective Estrogen Receptor Modulators - pharmacology; Stereoisomerism; Uterine Neoplasms; Uterus - drug effects; Uterus - growth & development; HCL; LY117018; TRIAL; ANTIESTROGENS; RAT; RALOXIFENE; TAMOXIFEN; SYMPTOMS; LY-117018; HYDROCHLORIDE; Estrogen receptor; Skin disease; Rat; Menopause; Cardiovascular disease; Hot flush; Vascular disease; Selective estrogen receptor modulator; Asymmetric synthesis; Piperidine derivatives; Mammary gland; Chemical synthesis; Tumor cell; Human; Modulator; Rodentia; Cholesterol; Vertebrata; Mammalia; Cell line; Treatment; Animal; Phenols; Bone mineral density; Fluorine Organic compounds; Antilipemic agent; Hormonal receptor
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm0509795

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 ERα and ERβ 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.