Kazuhide Konishi
Novartis
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Publication
Featured researches published by Kazuhide Konishi.
Bioorganic & Medicinal Chemistry Letters | 2008
Osamu Irie; Takatoshi Kosaka; Masashi Kishida; Junichi Sakaki; Keiichi Masuya; Kazuhide Konishi; Fumiaki Yokokawa; Takeru Ehara; Atsuko Iwasaki; Yuki Iwaki; Yuko Hitomi; Atsushi Toyao; Hiroki Gunji; Naoki Teno; Genji Iwasaki; Hajime Hirao; Takanori Kanazawa; Keiko Tanabe; Peter Hiestand; Marzia Malcangio; Alyson Fox; Stuart Bevan; Mohammed Yaqoob; Andrew James Culshaw; Terance Hart; Allan Hallett
We describe here orally active and brain-penetrant cathepsin S selective inhibitors, which are virtually devoid of hERG K(+) channel affinity, yet exhibit nanomolar potency against cathepsin S and over 100-fold selectivity to cathepsin L. The new non-peptidic inhibitors are based on a 2-cyanopyrimidine scaffold bearing a spiro[3.5]non-6-yl-methyl amine at the 4-position. The brain-penetrating cathepsin S inhibitors demonstrate potential clinical utility for the treatment of multiple sclerosis and neuropathic pain.
Bioorganic & Medicinal Chemistry Letters | 2008
Osamu Irie; Fumiaki Yokokawa; Takeru Ehara; Atsuko Iwasaki; Yuki Iwaki; Yuko Hitomi; Kazuhide Konishi; Masashi Kishida; Atsushi Toyao; Keiichi Masuya; Hiroki Gunji; Junichi Sakaki; Genji Iwasaki; Hajime Hirao; Takanori Kanazawa; Keiko Tanabe; Takatoshi Kosaka; Terance Hart; Allan Hallett
We describe here a novel 4-amino-2-cyanopyrimidine scaffold for nonpeptidomimetic cathepsin S selective inhibitors. Some of the synthesized compounds have sub-nanomolar potency and high selectivity toward cathepsin S along with promising pharmacokinetic and physicochemical properties. The key structural features of the inhibitors consist of a combination of a spiro[2.5]oct-6-ylmethylamine P2 group at the 4-position, a small or polar P3 group at the 5-position and/or a polar group at the 6-position of the pyrimidine.
ACS Medicinal Chemistry Letters | 2014
Takeru Ehara; Osamu Irie; Takatoshi Kosaka; Takanori Kanazawa; Werner Breitenstein; Philipp Grosche; Nils Ostermann; Masaki Suzuki; Shimpei Kawakami; Kazuhide Konishi; Yuko Hitomi; Atsushi Toyao; Hiroki Gunji; Frederic Cumin; Nikolaus Schiering; Trixie Wagner; Dean F. Rigel; Randy Lee Webb; Jürgen Maibaum; Fumiaki Yokokawa
A cis-configured 3,5-disubstituted piperidine direct renin inhibitor, (syn,rac)-1, was discovered as a high-throughput screening hit from a target-family tailored library. Optimization of both the prime and the nonprime site residues flanking the central piperidine transition-state surrogate resulted in analogues with improved potency and pharmacokinetic (PK) properties, culminating in the identification of the 4-hydroxy-3,5-substituted piperidine 31. This compound showed high in vitro potency toward human renin with excellent off-target selectivity, 60% oral bioavailability in rat, and dose-dependent blood pressure lowering effects in the double-transgenic rat model.
Bioorganic & Medicinal Chemistry Letters | 2007
Junichi Sakaki; Kazuhide Konishi; Masashi Kishida; Hiroki Gunji; Takanori Kanazawa; Hidefumi Uchiyama; Hiroaki Fukaya; Hironobu Mitani; Masaaki Kimura
Bioorganic & Medicinal Chemistry Letters | 2007
Junichi Sakaki; Masashi Kishida; Kazuhide Konishi; Hiroki Gunji; Atsushi Toyao; Yuki Matsumoto; Takanori Kanazawa; Hidefumi Uchiyama; Hiroaki Fukaya; Hironobu Mitani; Yoshie Arai; Masaaki Kimura
Archive | 2006
Junichi Sakaki; Masashi Kishida; Naoko Matsuura; Ichiro Umemura; Eiji Kawahara; Ken Yamada; Kazuhide Konishi; Yuki Iwaki; Hidetomo Imase; Takahiro Miyake
Archive | 2006
Takeru Ehara; Philipp Grosche; Osamu Irie; Yuki Iwaki; Takanori Kanazawa; Shimpei Kawakami; Kazuhide Konishi; Muneto Mogi; Masaki Suzuki; Fumiaki Yokokawa
Archive | 2004
Junichi Sakaki; Kazuhide Konishi; Masashi Kishida; Masaaki Kimura; Hidefumi Uchiyama; Hironobu Mitani
Archive | 2007
Kazuhide Konishi; Yuki Iwaki
Archive | 2006
Takeru Ehara; Yuko Hitomi; Kazuhide Konishi; Kelichi Masuya