Ryota Shiraki
Astellas Pharma
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Publication
Featured researches published by Ryota Shiraki.
Bioorganic & Medicinal Chemistry | 2012
Masakazu Imamura; Keita Nakanishi; Takayuki Suzuki; Kazuhiro Ikegai; Ryota Shiraki; Takashi Ogiyama; Takeshi Murakami; Eiji Kurosaki; Atsushi Noda; Yoshinori Kobayashi; Masayuki Yokota; Tomokazu Koide; Kazuhiro Kosakai; Yasufumi Ohkura; Makoto Takeuchi; Hiroshi Tomiyama; Mitsuaki Ohta
A series of C-glucosides with various heteroaromatics has been synthesized and its inhibitory activity toward SGLTs was evaluated. Upon screening several compounds, the benzothiophene derivative (14a) was found to have potent inhibitory activity against SGLT2 and good selectivity versus SGLT1. Through further optimization of 14a, a novel benzothiophene derivative (14h; ipragliflozin, ASP1941) was discovered as a highly potent and selective SGLT2 inhibitor that reduced blood glucose levels in a dose-dependent manner in diabetic models KK-A(y) mice and STZ rats.
Bioorganic & Medicinal Chemistry | 2008
Kenichi Onda; Takayuki Suzuki; Ryota Shiraki; Yasuhiro Yonetoku; Kenji Negoro; Kazuhiro Momose; Naoko Katayama; Masaya Orita; Tomohiko Yamaguchi; Mitsuaki Ohta; Shin-ichi Tsukamoto
A series of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives were prepared and evaluated as inhibitors of human liver glycogen phosphorylase a (hLGPa). One compound, 5-chloro-N-[4-(1,2-dihydroxyethyl)phenyl]-1H-indole-2-carboxamide (2f), inhibited hLGPa with an IC(50) of 0.90microM. The pyridine analogue of 2f showed inhibitory activity of glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) of 0.62microM and oral hypoglycemic activity in diabetic db/db mice. Crystallographic determination of the complex of 2f with hLGPa showed binding of the inhibitor in a solvent cavity at the dimer interface, with the two hydroxyl groups making favorable electrostatic interactions with hLGPa.
Bioorganic & Medicinal Chemistry | 2008
Kenichi Onda; Ryota Shiraki; Takashi Ogiyama; Kazuhiro Yokoyama; Kazuhiro Momose; Naoko Katayama; Masaya Orita; Tomohiko Yamaguchi; Masako Furutani; Noritaka Hamada; Makoto Takeuchi; Minoru Okada; Mitsuaki Ohta; Shin-ichi Tsukamoto
As a result of the various N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives with a hydroxy moiety synthesized in an effort to discover novel glycogen phosphorylase (GP) inhibitors, 5-chloro-N-(5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide (5b) was found to have potent inhibitory activity. The introduction of fluorine atoms both at a position adjacent to the hydroxy group and in the central benzene moiety lead to the optically active derivative 5-chloro-N-[(5R)-1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1H-indole-2-carboxamide (25e(alpha), which was the most potent compound in this series (IC(50)=0.020microM). This compound inhibited glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) value of 0.69microM, and showed oral hypoglycemic activity in diabetic db/db mice at 10mg/kg. Compound 25e(alpha) also had an excellent pharmacokinetic profile, with high oral bioavailability and a long plasma half-life, in male SD rats. The binding mode of 25e(alpha) to this molecule and the role of fluorine atoms in that binding were speculated in an enzyme docking study.
Archive | 2004
Masakazu Imamura; Takeshi Murakami; Ryota Shiraki; Kazuhiro Ikegai; Takashi Sugane; Fumiyoshi Iwasaki; Eiji Kurosaki; Hiroshi Tomiyama; Atsushi Noda; Kayoko Kitta; Yoshinori Kobayashi
Archive | 2009
Takeshi Murakami; Tomoaki Kawano; Ryota Shiraki; Hirofumi Ishii; Seiji Yoshimura; Takehiko Ohkawa; Mitsuru Hosaka; Hiroki Fukudome; Yutaka Inoki
Archive | 2007
Masakazu Imamura; Keita Nakanishi; Ryota Shiraki; Kenichi Onda; Daisuke Sasuga; Masamichi Yuda
Archive | 2003
Kenichi Onda; Takayuki Suzuki; Ryota Shiraki; Yasuhiro Yonetoku; Takashi Ogiyama; Tatsuya Maruyama; Kazuhiro Momose
Archive | 2001
Fukushi Hirayama; Hiroyuki Koshio; Tsukasa Ishihara; Norio Seki; Shunichiro Hachiya; Keizo Sugasawa; Ryota Shiraki; Yuji Koga; Yuzo Matsumoto; Takeshi Shigenaga; Souichirou Kawazoe
Archive | 2002
Tatsuya Maruyama; Kazuhiro Momose; Takashi Ogiyama; Kenichi Onda; Ryota Shiraki; Takayuki Suzuki; 龍也 丸山; 健一 恩田; 良太 白木; 和浩 百▲瀬▼; ▲隆▼ 荻山; 貴之 鈴木
Archive | 2007
Kousuke Komenoi; Atsushi Nakamura; Makoto Kasai; Masakazu Imamura; Ryota Shiraki; Keita Nakanishi