-transparent.png){kind=logo}
Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P₁ agonists. 2014
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
Medicinal Chemistry Research Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats.
Related Publications
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
May 2012,
Bioorganic & medicinal chemistry letters,
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
July 1994,
Journal of medicinal chemistry,
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
June 2006,
Bioorganic & medicinal chemistry letters,
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
August 2021,
European journal of medicinal chemistry,
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
May 2012,
Journal of medicinal chemistry,
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
December 2012,
Bioorganic & medicinal chemistry letters,
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
November 2015,
Bioorganic & medicinal chemistry letters,
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
May 2012,
European journal of medicinal chemistry,
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
May 2010,
Journal of medicinal chemistry,
Takashi Tsuji, and
Keisuke Suzuki, and
Tsuyoshi Nakamura, and
Taiji Goto, and
Yukiko Sekiguchi, and
Takuya Ikeda, and
Takeshi Fukuda, and
Toshiyasu Takemoto, and
Yumiko Mizuno, and
Takako Kimura, and
Yumi Kawase, and
Futoshi Nara, and
Takashi Kagari, and
Takaichi Shimozato, and
Chizuko Yahara, and
Shinichi Inaba, and
Tomohiro Honda, and
Takashi Izumi, and
Masakazu Tamura, and
Takahide Nishi
October 2010,
ChemMedChem,
