title: Newly discovered orally active pure antiestrogens.
abstract: 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.
authors.affiliation: Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan. kanbeyst@chugai-pharm.co.jp
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Kanbe
authors.forename: Myung-Hwa
authors.initials: MH
authors.lastname: Kim
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishimoto
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ohtake
authors.forename: Takaaki
authors.initials: T
authors.lastname: Yoneya
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohizumi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tsunenari
authors.forename: Kenji
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kaiho
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nabuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Araya
authors.forename: Setsu
authors.initials: S
authors.lastname: Kawata
authors.forename: Kazumi
authors.initials: K
authors.lastname: Morikawa
authors.forename: Jae-Chon
authors.initials: JC
authors.lastname: Jo
authors.forename: Hee-An
authors.initials: HA
authors.lastname: Kwon
authors.forename: Hyun-Suk
authors.initials: HS
authors.lastname: Lim
authors.forename: Hak-Yeop
authors.initials: HY
authors.lastname: Kim
mesh_terms: 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
chemical_list: D020847:Estrogen Receptor Modulators; D013256:Steroids