title: Design, synthesis, and biological evaluation of novel estradiol-bisphosphonate conjugates as bone-specific estrogens.
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.
authors.affiliation: Medicinal Chemistry Laboratory, Research Division, Mitsubishi-Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Morioka
authors.forename: Akihito
authors.initials: A
authors.lastname: Kamizono
authors.forename: Hirosato
authors.initials: H
authors.lastname: Takikawa
authors.forename: Akihisa
authors.initials: A
authors.lastname: Mori
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ueno
authors.forename: Shu-ichiro
authors.initials: S
authors.lastname: Kadowaki
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Nakao
authors.forename: Kuniki
authors.initials: K
authors.lastname: Kato
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
mesh_terms: 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
chemical_list: D004164:Diphosphonates; D011960:Receptors, Estrogen; D004958:Estradiol