- GLUCOSE TRANSPORT INHIBITORS
-
The present invention relates to chemical compounds of general formula (I): in which RA, RB, RC, RD, m, and n are as given in the description and in the claims, and which effectively and selectively inhibit glucose transporter 1 (GLUT1), to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.
- -
-
Page/Page column 141; 142
(2014/01/08)
-
- Development of a practical synthesis of a pyrazolopyridinone-based p38 MAP kinase inhibitor
-
A practical synthesis of the pyrazolopyridinone-based p38 MAP kinase inhibitor (4) was required for an ongoing program. The synthesis of a key pyrazolopyridinone building block was refined and optimized to provide kilogram quantities of 10 without chromat
- Milburn, Robert R.,Thiel, Oliver R.,Achmatowicz, Michal,Wang, Xiang,Zigterman, Jamie,Bernard, Charles,Colyer, John T.,Divirgilio, Evan,Crockett, Rich,Correll, Tiffany L.,Nagapudi, Karthik,Ranganathan, Kumar,Hedley, Simon J.,Allgeier, Alan,Larsen, Robert D.
-
experimental part
p. 31 - 43
(2011/09/21)
-
- Discovery and evaluation of 7- lkyl-1,5-bis-aryl-pyrazolopyridinones as Highly potent, selective, and orally efficacious inhibitors of p38α mitogen-activated protein kinase
-
The p38α mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1- and tumor necrosis factor α. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn's disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl- pyrazolopyridinone-based p38α inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED50 - 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.
- Pettus, Liping H.,Wurz, Ryan P.,Xu, Shimin,Herberich, Brad,Henkle, Bradley,Liu, Qiurong,McBride, Helen J.,Mu, Sharon,Plant, Matthew H.,Saris, Christiaan J.M.,Sherman, Lisa,Wong, Lu Min,Chmait, Samer,Lee, Matthew R.,Mohr, Christopher,Hsieh, Faye,Tasker, Andrew S.
-
experimental part
p. 2973 - 2985
(2010/09/05)
-
- PYRAZOLO-PYRAZINONE COMPOUNDS AND METHODS OF USE THEREOF
-
The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula (I) wherein A1, B, R
- -
-
Page/Page column 44
(2009/10/22)
-