| Literature DB >> 15225718 |
Toshiki Murata1, Mitsuyuki Shimada, Sachiko Sakakibara, Takashi Yoshino, Tsutomu Masuda, Takuya Shintani, Hiroki Sato, Yuji Koriyama, Keiko Fukushima, Noriko Nunami, Megumi Yamauchi, Kinji Fuchikami, Hiroshi Komura, Akihiko Watanabe, Karl B Ziegelbauer, Kevin B Bacon, Timothy B Lowinger.
Abstract
A series of 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl)pyridine derivatives was synthesized and evaluated as I kappaB kinase beta (IKK-beta) inhibitors. Modification of a novel IKK-beta inhibitor 1 (IKK-beta IC(50)=1500 nM, Cell IC(50)=8000 nM) at the 4-phenyl ring and 6-phenol group on the pyridine core ring resulted in a marked increased in biological activities. An optimized compound, 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinonitrile, exhibited excellent in vitro profiles (IKK-beta IC(50)=8.5 nM, Cell IC(50)=60 nM) and a strong oral efficacy in in vivo anti-inflammatory assays (significant effects at 1mg/kg, po in arachidonic acid-induced ear edema model in mice).Entities:
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Year: 2004 PMID： 15225718 DOI： 10.1016/j.bmcl.2004.05.041
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823