Kousei Yoshihara
Astellas Pharma
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Publication
Featured researches published by Kousei Yoshihara.
Bioorganic & Medicinal Chemistry | 2013
Takayuki Inoue; Masataka Morita; Takashi Tojo; Kousei Yoshihara; Akira Nagashima; Ayako Moritomo; Mitsuru Ohkubo; Hiroshi Miyake
Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema. In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC(50) of 230 nM; rat IC(50) of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats.
Bioorganic & Medicinal Chemistry | 2018
Toshihiro Hamajima; Fumie Takahashi; Koji Kato; Koichiro Mukoyoshi; Kousei Yoshihara; Susumu Yamaki; Yukihito Sugano; Ayako Moritomo; Kaoru Yamagami; Koji Yokoo; Hidehiko Fukahori
Phosphatidylinositol-3-kinase (PI3K)δ inhibition is one of the most attractive approaches to the treatment of autoimmune diseases and leukocyte malignancies. Through the exploration of pyrazolopyridine derivatives as potential PI3Kδ inhibitors, compound 12a was identified as a potent PI3Kδ inhibitor but suffered from poor oral exposure in mice. With a modified amide linkage group, compound 15a was developed as an orally available PI3Kδ inhibitor with reduced selectivity against other PI3Ks. To improve the trade-off between selectivity and PK profile, structure-activity relationship (SAR) studies of terminal substituents on the pyrolidine ring were conducted. As a result, we developed potent PI3Kδ inhibitors with good oral availability. In particular, the representative compound 15j showed excellent selectivity for PI3Kδ over other PI3Ks with good oral exposure in mice.
Archive | 2006
Shunichiro Hachiya; Makoto Oku; Hana Mukai; Takashi Shin; Keisuke Matsuura; Ryushi Seo; Takashi Kamikubo; Yoh Terada; Masanao Sanagi; Kousei Yoshihara; Taisuke Takahashi
Archive | 2004
Ryuji Ueno; Akira Nagashima; Takayuki Inoue; Mitsuru Ohkubo; Kousei Yoshihara
Archive | 2004
Takayuki Inoue; Takashi Tojo; Masataka Morita; Mitsuru Ohkubo; Kousei Yoshihara; Akira Nagashima
Archive | 1999
Ichiro Shima; Takehiko Ohkawa; Kazuhiko Ohne; Tatsuya Zenko; Teruo Oku; Kousei Yoshihara; Hiroyuki Setoi
Archive | 2006
Shunichiro Hachiya; Makoto Oku; Hana Mukai; Takashi Shin; Keisuke Matsuura; Ryushi Seo; Takashi Kamikubo; Yoh Terada; Masanao Sanagi; Kousei Yoshihara; Taisuke Takahashi
Archive | 2006
Shunichiro Hachiya; Makoto Oku; Misawa Hana Mukai; Takashi Shin; Keisuke Matsuura; Ryushi Seo; Takashi Kamikubo; Yoh Terada; Masanao Sanagi; Kousei Yoshihara; Taisuke Takahashi
Archive | 2004
Ryuji Ueno; Akira Nagashima; Takayuki Inoue; Mitsuru Ohkubo; Kousei Yoshihara
Archive | 1997
Yoshikuni Itoh; Takayuki Inoue; Hitoshi Hamashima; Ichiro Shima; Kazuhiko Ohne; Kousei Yoshihara; Teruo Oku; Takumi Yatabe