Newly discovered orally active pure antiestrogens.
In order to develop orally active pure antiestrogens, we incorporated the carboxy-containing side chains into the 7alpha-position of the steroid scaffold and found that 17-keto derivative CH4893237 (12b) functioned as a pure antiestrogen with its oral activity much superior to clinically used pure antiestrogen, ICI182,780. Results from the pharmacokinetic evaluation indicated that the potent antiestrogen activity at oral dosing in mice attributed to both improved absorption from the intestinal wall and metabolic stability in liver.
Kanbe
Yoshitake
Y
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan. kanbeyst@chugai-pharm.co.jp
Kim
Myung-Hwa
MH
Nishimoto
Masahiro
M
Ohtake
Yoshihito
Y
Yoneya
Takaaki
T
Ohizumi
Iwao
I
Tsunenari
Toshiaki
T
Taniguchi
Kenji
K
Kaiho
Shin-ichi
S
Nabuchi
Yoshiaki
Y
Araya
Hiroshi
H
Kawata
Setsu
S
Morikawa
Kazumi
K
Jo
Jae-Chon
JC
Kwon
Hee-An
HA
Lim
Hyun-Suk
HS
Kim
Hak-Yeop
HY
D000284:Administration, Oral; D000818:Animals; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000882:Haplorhini; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D020847:Estrogen Receptor Modulators; D013256:Steroids