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Pure Appl. Chem., 2003, Vol. 75, No. 9, pp. 1197-1205

Boron clusters for medicinal drug design: Selective estrogen receptor modulators bearing carborane

Yasuyuki Endo1, Tomohiro Yoshimi1 and Chisato Miyaura2

1 Tohoku Pharmaceutical University, Sendai 981-8558, Japan
2 Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan

Abstract: The molecular shape and hydrophobicity of dicarba-closo -dodecaboranes may allow a new medical application as biologically active molecules. Recently, we have developed potent estrogen receptor (ER) agonists bearing carborane cage. The most potent compound (BE120) exhibited activity at least several times greater than that of 17 beta-estradiol in luciferase reporter gene assay and ER alpha binding. We also designed and synthesized estrogen antagonists on the basis of the structure of BE120, and we noticed the characteristic features of compound (BE360) having carborane cage and two phenols. The ER binding affinity of BE360 is comparable to that of estradiol. To examine in vivo estrogenic activity of the compound in bone, ovariectomized (OVX) mice were given BE360 or estradiol subcutaneously for 4 weeks. Treatment with BE360 at 1–30 µg/day dose-dependently restored bone loss in OVX mice to sham level without estrogenic action in uterus. These results suggest its possible application to osteoporosis as a new type of selective ER modulator.