Synthesis and pharmacology of 2-alkyl raloxifene analogs

✍ Scribed by Timothy A. Grese; Stephen Cho; Henry U. Bryant; Harlan W. Cole; Andrew L. Glasebrook; David E. Magee; D.Lynn Phillips; Ellen R. Rowley; Lorri L. Short

• Publisher: Elsevier Science
• Year: 1996
• Tongue: English
• Weight: 290 KB
• Volume: 6
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/0960-894x(95)00575-e

✦ Synopsis

A series of 2-alkyl and 2-cycioalkyl raloxifene analogs have been prepared and evaluated in both in vitro and in vivo models of estrogen/antiestrogen activity. In particular, the 2-cyclohexyl analogs show promise as potent sdective estrogen-receptor modulators (SERMs).

The decreased production of ovarian steroids which occurs after the climacteric has been linked to a number of post-menopausal pathologies, particularly osteoporosis and coronary artery disease. 1,2 Estrogen replacement therapy has demonstrated effectiveness in reducing the risks associated with these pathologies, however concerns relating to the increased risk of endometrial cancer have necessitated the development of therapeutic regimens in which the uterine effects of estrogen are opposed by progestin treatment. 3 Sideeffects of progestin treatment, such as resumption of menses, and the possibility of attenuated cardiovascular benefits have significantly affected patient compliance. 4 Furthermore, recent studies which confirm the increased risk of breast cancer associated with estrogen replacement therapy have led to the search for treatment alternatives.5 O o.