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Dive into the research topics where Masahiro Nishimoto is active.

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Featured researches published by Masahiro Nishimoto.


Journal of Medicinal Chemistry | 2012

Discovery of Tofogliflozin, a Novel C-Arylglucoside with an O-Spiroketal Ring System, as a Highly Selective Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes

Yoshihito Ohtake; Tsutomu Sato; Takamitsu Kobayashi; Masahiro Nishimoto; Naoki Taka; Koji Takano; Keisuke Yamamoto; Masayuki Ohmori; Marina Yamaguchi; Kyoko Takami; Sang-Yong Yeu; Koo-Hyeon Ahn; Hiroharu Matsuoka; Kazumi Morikawa; Masayuki Suzuki; Hitoshi Hagita; Kazuharu Ozawa; Koji Yamaguchi; Motohiro Kato; Sachiya Ikeda

Inhibition of sodium glucose cotransporter 2 (SGLT2) has been proposed as a novel therapeutic approach to treat type 2 diabetes. In our efforts to discover novel inhibitors of SGLT2, we first generated a 3D pharmacophore model based on the superposition of known inhibitors. A search of the Cambridge Structural Database using a series of pharmacophore queries led to the discovery of an O-spiroketal C-arylglucoside scaffold. Subsequent chemical examination combined with computational modeling resulted in the identification of the clinical candidate 16d (CSG452, tofogliflozin), which is currently under phase III clinical trials.


Bioorganic & Medicinal Chemistry | 2011

5a-Carba-β-D-glucopyranose derivatives as novel sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes.

Yoshihito Ohtake; Tsutomu Sato; Hiroharu Matsuoka; Masahiro Nishimoto; Naoki Taka; Koji Takano; Keisuke Yamamoto; Masayuki Ohmori; Takashi Higuchi; Masatoshi Murakata; Takamitsu Kobayashi; Kazumi Morikawa; Nobuo Shimma; Masayuki Suzuki; Hitoshi Hagita; Kazuharu Ozawa; Koji Yamaguchi; Motohiro Kato; Sachiya Ikeda

5a-Carba-β-D-glucopyranose derivatives were synthesized and identified as novel SGLT2-selective inhibitors. These inhibitors exhibited potent SGLT2 inhibition with high selectivity over SGLT1. Among the tested compounds, 6f indicated the most potent hSGLT2 inhibition and the highest selectivity over hSGLT1. Moreover, the pharmacokinetics data also showed that 6h, which had the same aglycon structure as sergliflozin-active (3-active), had a threefold longer half-life time (T(1/2)) than sergliflozin (3) with a high distribution volume in db/db mice. Subsequently, 6h lowered blood glucose levels as much as 3 and showed longer hypoglycemic action than 3 in db/db mice.


Bioorganic & Medicinal Chemistry | 2012

C-Aryl 5a-carba-β-d-glucopyranosides as novel sodium glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes.

Yoshihito Ohtake; Tsutomu Sato; Hiroharu Matsuoka; Takamitsu Kobayashi; Masahiro Nishimoto; Naoki Taka; Koji Takano; Keisuke Yamamoto; Masayuki Ohmori; Takashi Higuchi; Masatoshi Murakata; Kazumi Morikawa; Nobuo Shimma; Masayuki Suzuki; Hitoshi Hagita; Kazuharu Ozawa; Koji Yamaguchi; Motohiro Kato; Sachiya Ikeda

C-Aryl 5a-carba-β-d-glucopyranose derivatives were synthesized and evaluated for inhibition activity against hSGLT1 and hSGLT2. Modifications to the substituents on the two benzene rings resulted in enhanced hSGLT2 inhibition activity and extremely high hSGLT2 selectivity versus SGLT1. Using the created superimposed model, the reason for the high hSGLT2 selectivity was speculated to be that additional substituents occupied a new space, in a different way than known inhibitors. Among the tested compounds, the ethoxy compound 5h with high hSGLT2 selectivity exhibited more potent and longer hypoglycemic action in db/db mice than our O-carbasugar compound (1) and sergliflozin (2), which could be explained by its improved PK profiles relative to those of the two compounds. These results indicated that 5h might be a promising drug candidate for the treatment of type 2 diabetes.


Journal of Organic Chemistry | 2016

Development of a Scalable Synthesis of Tofogliflozin

Yoshihito Ohtake; Takashi Emura; Masahiro Nishimoto; Koji Takano; Keisuke Yamamoto; Satoshi Tsuchiya; Sang-Yong Yeu; Yasushi Kito; Nobuaki Kimura; Sunao Takeda; Masao Tsukazaki; Masatoshi Murakata; Tsutomu Sato

An efficient and scalable synthesis of an antidiabetic drug, tofogliflozin (1), which was identified as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor, is described. A key factor in the synthesis of 1 was the selection of the purpose-designed protecting group, which plays a strategic role in protection, chemoselective activation, and crystalline purification. The developed and optimized method made it possible to prepare 1 on a multidecagram scale without any column chromatography.


Archive | 2005

Novel Cyclohexane Derivative, Prodrug Thereof and Salt Thereof, and Therapeutic Agent Containing the Same for Diabetes

Hiroharu Matsuoka; Tsutomu Sato; Masahiro Nishimoto; Nobuo Shimma


Archive | 1991

Novel benzopyran derivatives

Jae Chon Jo; Sung Dae Park; Hyun Suk Lim; Ju Su Kim; Sungjin Kim; Kazumi Morikawa; Yoshitake Kanbe; Masahiro Nishimoto; Myunghwa Kim


Archive | 2006

Spiroketal derivatives and use thereof as diabetic medicine

Takamitsu Kobayashi; Tsutomu Sato; Masahiro Nishimoto


Journal of Medicinal Chemistry | 2006

Discovery of potent and orally available malonyl-CoA decarboxylase inhibitors as cardioprotective agents.

Jie-Fei Cheng; Yujin Huang; Richard Penuliar; Masahiro Nishimoto; Larry Liu; Thomas Arrhenius; Guang Yang; Eoin O'leary; Miguel Barbosa; Rick L. Barr; Jason R. B. Dyck; Gary D. Lopaschuk; Alex M. Nadzan


Bioorganic & Medicinal Chemistry Letters | 2006

Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens

Yoshitake Kanbe; Myung Hwa Kim; Masahiro Nishimoto; Yoshihito Ohtake; Toshiaki Tsunenari; Kenji Taniguchi; Iwao Ohizumi; Shin ichi Kaiho; Yoshiaki Nabuchi; Setsu Kawata; Kazumi Morikawa; Jae Chon Jo; Hee An Kwon; Hyun Suk Lim; Hak Yeop Kim


Archive | 2007

Fused ring spiroketal derivative and use thereof as drug for treating diabetes

Tsutomu Sato; Yoshihito Ohtake; Masahiro Nishimoto; Takashi Emura; Takamitsu Kobayashi; Marina Yamaguchi; Kyouko Takami

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Kazumi Morikawa

Chugai Pharmaceutical Co.

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Yoshitake Kanbe

Chugai Pharmaceutical Co.

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Tsutomu Sato

Chugai Pharmaceutical Co.

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Myunghwa Kim

Chugai Pharmaceutical Co.

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Hyun Suk Lim

Chugai Pharmaceutical Co.

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Jaechon Jo

Chugai Pharmaceutical Co.

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Takashi Emura

Chugai Pharmaceutical Co.

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