Benzothiophene Selective Estrogen Receptor Modulators with Modulated Oxidative Activity and Receptor Affinity
Citations Over TimeTop 10% of 2007 papers
Abstract
The regulation of estrogenic and antiestrogenic effects of selective estrogen receptor modulators (SERMs) is thought to underlie their clinical use. Most SERMs are polyaromatic phenols susceptible to oxidative metabolism to quinoids, which are proposed to be genotoxic. Conversely, the redox reactivity of SERMs may contribute to antioxidant and chemopreventive mechanisms, providing a new approach to improve the therapeutic properties of SERMs. An improved synthetic strategy was developed to generate a family of benzothiophene SERMs. Using computational modeling methods and measurements of antioxidant activity and estrogen receptor (ER) ligand binding, this SERM family was shown to provide both a range of ERalpha/ERbeta selectivity from 1.2- to 67-fold and a range of redox activity. Antioxidant activity was successfully modulated by varying a substituent remote from the OH group; the source of the antioxidant capacity. An efficient synthetic procedure is reported yielding benzothiophene SERMs wherein redox activity and ER affinity are modulated.
Related Papers
- → Raloxifene: A Selective Estrogen Receptor Modulator (SERM) with Multiple Target System Effects(2000)135 cited
- → In Search of Optimal Long-Term Female Hormone Replacement: The Potential of Selective Estrogen Receptor Modulators(1997)131 cited
- [Clinical experience with raloxifene].(2000)
- [Evidence for the selective estrogen receptor modulator raloxifene: its evolving role in the treatment of osteoporosis].(2008)
- Growth Inhibition of Human Uterine Leiomyoma Cells by Selective Estrogen Receptor Modulator(2004)