title: Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
abstract: In order to search for alternatives to the sulfoxide moiety in the long side chain of pure antiestrogens, several molecules that may interact with water in a fashion similar to ICI164,384 were designed and it was found that compounds with the carboxy, the sulfamide, or the sulfonamide instead of the sulfoxide moiety also functioned as pure antiestrogens. Interestingly, the compound possessing the carboxy moiety showed superior antiestrogen activity compared to ICI182,780 when dosed orally. Results of the pharmacokinetic evaluation indicated that the potent antiestrogen activity at oral dosing attributed to both the improved absorption from the intestinal wall and the metabolic stability of the compound 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: Toshiaki
authors.initials: T
authors.lastname: Tsunenari
authors.forename: Kenji
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohizumi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kaiho
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nabuchi
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; D019540:Area Under Curve; D002839:Chromans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D002839:Chromans; D020847:Estrogen Receptor Modulators