- The discovery of thienopyridine analogues as potent IκB kinase β inhibitors. Part II
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An SAR study that identified a series of thienopyridine-based potent IκB Kinase β (IKKβ) inhibitors is described. With focuses on the structural optimization at C4 and C6 of structure 1 (Fig. 1), the study reveals that small alkyl and certain aromatic groups are preferred at C4, whereas polar groups with proper orientation at C6 efficiently enhance compound potency. The most potent analogues inhibit IKKβ with IC50s as low as 40 nM, suppress LPS-induced TNF-α production in vitro and in vivo, display good kinase selectivity profiles, and are active in a HeLa cell NF-κB reporter gene assay, demonstrating that they directly interfere with the NF-κB signaling pathway.
- Wu, Jiang-Ping,Fleck, Roman,Brickwood, Janice,Capolino, Alison,Catron, Katrina,Chen, Zhidong,Cywin, Charles,Emeigh, Jonathan,Foerst, Melissa,Ginn, John,Hrapchak, Matt,Hickey, Eugene,Hao, Ming-Hong,Kashem, Mohammed,Li, Jun,Liu, Weimin,Morwick, Tina,Nelson, Richard,Marshall, Daniel,Martin, Leslie,Nemoto, Peter,Potocki, Ian,Liuzzi, Michel,Peet, Gregory W.,Scouten, Erika,Stefany, David,Turner, Michael,Weldon, Steve,Zimmitti, Clare,Spero, Denise,Kelly, Terence A.
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scheme or table
p. 5547 - 5551
(2010/04/05)
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- THIENOPYRIDINE DERIVATIVES
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The present invention provides a compound promoting osteogenesis. The present invention provides a compound having the following general formula (I) wherein R 1 is H or alkyl, R 2 is R a S-, R a O-, R a NH-, R a (R b )N- or cyclic amino, and R a and R b are alkyl which may be substituted, cycloalkyl which may be substituted, or the like, or a pharmacologically acceptable salt thereof.
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Page/Page column 142-143
(2010/11/26)
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- ANTAGONISTS OF THE MGLU RECEPTOR AND USES THEREOF
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The present invention discloses compounds of general formula (I) wherein X1-X4 and R1-R3 are as defined in the description. The present invention also discloses methods of treatment for pain, neurodegeneration and convulsive states in a host mammal in need thereof, and pharmaceutical compositions including those compounds.
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Page/Page column 48
(2008/06/13)
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- FUSED FURAN COMPOUND
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The present invention provides a condensed furan compound of the formula (I): wherein Ring X is benzene, pyridine, or the like; Y is an optionally substituted amino, an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted saturated heterocyclic group, an optionally substituted unsaturated heterocyclic group; A is a single bond, lower alkylene, lower alkenylidene, lower alkenylene or an oxygen atom; R3 is hydrogen or the like; and , R4 is hydrogen, or the like, or pharmaceutically acceptable salts thereof, which is useful as a medicament, particularly, as an activated blood coagulation factor X inhibitor.
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Page/Page column 157
(2008/06/13)
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- Structure-activity relationship of triazafluorenone derivatives as potent and selective mGluR1 antagonists
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SAR (structure-activity relationship) studies of triazafluorenone derivatives as potent mGluR1 antagonists are described. The triazafluorenone derivatives are non-amino acid derivatives and noncompetitive mGluR1 antagonists that bind at a putative alloste
- Zheng, Guo Zhu,Bhatia, Pramila,Daanen, Jerome,Kolasa, Teodozyj,Patel, Meena,Latshaw, Steven,El Kouhen, Odile F.,Chang, Renjie,Uchic, Marie E.,Miller, Loan,Nakane, Masaki,Lehto, Sonya G.,Honore, Marie P.,Moreland, Robert B.,Brioni, Jorge D.,Stewart, Andrew O.
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p. 7374 - 7388
(2007/10/03)
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- SUBSTITUTED 3-AMINO-THIENO[2,3-b]PYRIDINE-2-CARBOXYLIC ACID AMIDE COMPOUNDS AND PROCESSES FOR PREPARING AND THEIR USES
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Disclosed are compounds of formula (I), wherein R1 and R2 are defined herein, which are useful as inhibitors of the kinase activity of the IκB kinase (IKK) complex. The compounds are therefore useful in the treatment of IKK mediated diseases including autoimmune diseases inflammatory diseases and cancer. Also disclosed are pharmaceutical compositions comprising these compounds and processes for preparing these compounds.
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