Design, synthesis, and biological evaluation of novel estradiol-bisphosphonate conjugates as bone-specific estrogens.
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.
Morioka
Masahiko
M
Medicinal Chemistry Laboratory, Research Division, Mitsubishi-Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
Kamizono
Akihito
A
Takikawa
Hirosato
H
Mori
Akihisa
A
Ueno
Hiroaki
H
Kadowaki
Shu-ichiro
S
Nakao
Yoshihide
Y
Kato
Kuniki
K
Umezawa
Kazuo
K
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D004164:Diphosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004958:Estradiol / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D010024:Osteoporosis / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D014599:Uterus / Q000187:drug effects
D004164:Diphosphonates; D011960:Receptors, Estrogen; D004958:Estradiol