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Published on: March 29, 2018
Design, synthesis, and biological evaluation of novel estradiol-bisphosphonate conjugates as bone-specific estrogens
Masahiko Morioka1, Akihito Kamizono, Hirosato Takikawa
1Medicinal Chemistry Laboratory, Research Division, Mitsubishi-Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
Abstract:
Bone deficiency causes osteoporosis and often decreases quality of life in patients with rheumatoid arthritis. Estrogens are known to protect elderly women from bone loss. Synthesis of new estradiol-bisphosphonate conjugates (E(2)-BPs) was accomplished and their in vivo activity as bone-specific estrogens were examined. Among them, MCC-565 showed selective estrogenic activity in bones; but it showed little estrogenic activity in the uterus. We also found that the linker moiety in E(2)-BPs was essential for the absorption and specificity of the conjugates.
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