Estrogenic activity of B-fluorinated o-carborane-1,2-bisphenol synthesized via S(N)Ar reaction.
We previously identified o-carborane bisphenol BE360 (4) as a selective estrogen receptor modulator (SERM), which ameliorated bone loss without inducing estrogenic action in uterus of OVX and ORX mice. Here, we synthesized a fluorinated derivative, B-fluorinated o-carborane bisphenol BE310 (5) by means of S(N)Ar reaction. Compound 5 was a partial ER agonist, like 4, with little change of ERα and ERβ selectivity as compared with 4. However, its agonistic activity was 40 times weaker than that of 4. Thus, 5 is a novel SERM candidate with potential for reduced estrogenic side effects, and in vivo evaluation as an anti-osteoporosis agent seems warranted.
Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Kiminori
K
Ohta
Takumi
T
Ogawa
Yasuyuki
Y
Endo
D000818:Animals; D001559:Benzhydryl Compounds; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000819:agonists*; D047629:Estrogen Receptor beta / Q000819:agonists*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000098851:Carboranes
D001559:Benzhydryl Compounds; D001896:Boron Compounds; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; C576913:BE310 carborane; D000098851:Carboranes; C513207:m-bis(hydroxyphenyl)carborane