- Microwave-assisted efficient synthesis of pyrazole-fibrate derivatives as stimulators of glucose uptake in skeletal muscle cells
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The design and synthesis of a series of pyrazolo[3,4-d]pyrimidinones containing fibrate side chains have been accomplished by utilizing the concept of molecular hybridization. All the synthesized compounds were evaluated for the glucose uptake stimulatory effect in L6 rat skeletal muscle cells. Four compounds (3f, 3g, 3j and 3q) were found to show significant stimulation of glucose uptake. Further these four compounds have been examined for their Glut4 translocation stimulatory effect in L6-Glut4myc myotubes. Compound 3q was found to exert maximum increase in GLUT4myc translocation.
- Gupta, Sampa,Kant, Ruchir,Pandey, Shubham,Rai, Amit Kumar,Sashidhara, Koneni V.,Singh, L. Ravithej,Tamrakar, Akhilesh K.
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- Development of a practical synthesis of a pyrazolopyridinone-based p38 MAP kinase inhibitor
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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.
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experimental part
p. 31 - 43
(2011/09/21)
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- 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
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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.
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experimental part
p. 2973 - 2985
(2010/09/05)
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- 1, 5-DIHYDRO-PYRAZOLO (3, 4-D) PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS PDE9A MODULATORS FOR THE TEATMENT OF CNS DISORDERS
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The invention relates to novel substituted pyrazolopyrimidines. Chemically, the compounds are characterised by general Formula (I): with R1 being phenyl or pyridyl, any of which is substituted with 1 to 4, preferably 1 to 3 substituents X; X in
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Page/Page column 59
(2009/07/03)
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- NOVEL COMPOUNDS
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The present invention provides compounds of formula (I): a process for their preparation, to pharmaceutical compositions comprising the compounds and the preparation of said compositions, to intermediates, and to use of the compounds for the manufacture of a medicament for therapeutic treatment, particularly for the treatment of inflammation and/or allergic conditions.
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Page/Page column 34-35
(2009/06/27)
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- Microwave-assisted protocols for the expedited synthesis of pyrazolo[1,5-a] and [3,4-d]pyrimidines
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General, high-yielding MAOS protocols for the expedited synthesis of functionalized pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-b]pyrimidines, as well as their pyrazole precursors, are described amenable to an iterative analogue library synthesis strategy for lead optimization.
- Daniels, R. Nathan,Kim, Kwangho,Lebois, Evan P.,Muchalski, Hubert,Hughes, Mary,Lindsley, Craig W.
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p. 305 - 310
(2008/09/17)
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- PYRAZOLO-PYRIMIDINE DERIVATIVES AS ANTI-INFLAMMATORY AGENTS
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The present invention is directed to compounds of formula (I): a process for their preparation, to pharmaceutical compositions comprising the compounds and the preparation of said compositions, to intermediates and to use of the compounds for the manufacture of a medicament for therapeutic treatment, particularly for the treatment of inflammation and/or allergic conditions.
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Page/Page column 41
(2008/06/13)
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