Kanbe Yoshitake, Kim Myung-Hwa, Nishimoto Masahiro, Ohtake Yoshihito, Kato Nobuaki, Tsunenari Toshiaki, Taniguchi Kenji, Ohizumi Iwao, Kaiho Shin-ichi, Morikawa Kazumi, Jo Jae-Chon, Lim Hyun-Suk, Kim Hak-Yeop
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan.
Bioorg Med Chem. 2006 Jul 15;14(14):4803-19. doi: 10.1016/j.bmc.2006.03.020. Epub 2006 Mar 31.
In order to develop pure antiestrogens, a series of 7-hydroxy-3-(4-hydroxyphenyl)-3-methylchroman and 7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman derivatives with sulfoxide containing side chains at the 4-position were designed, synthesized, and evaluated. Among them, compounds 14b and 24b functioned as pure antiestrogens with the ability to downregulate ER, and their in vitro and in vivo antiestrogen activities were similar to those of ICI182,780. In addition, the structure-activity relationship indicated that the (3RS,4RS)-configuration between the 3- and 4-position, the methyl group at the 3-position, the 9-methylene chain between the scaffold and the sulfoxide moiety, and the terminal perfluoroalkyl moiety play an important role in increasing estrogen receptor binding and oral antiestrogen activities.
