50590-07-3Relevant academic research and scientific papers
HETEROARYL COMPOUNDS AS PDE10A INHIBITORS
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Page/Page column 42, (2011/11/06)
The present invention provides heteroaryl compounds as Phosphodiesterase 10A (PDE I OA) inhibitors. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders by inhibiting Phosphodiesterase 10A enzyme. Also provided herein are processes for preparing compounds described herein, Formula (I), intermediates used in their synthesis, pharmaceutical compositions thereof.
A Pd[0]-catalyzed Ullmann cross-coupling/reductive cyclization approach to C-3 mono-alkylated oxindoles and related compounds
Banwell, Martin G.,Jones, Matthew T.,Loong, David T.J.,Lupton, David W.,Pinkerton, David M.,Ray, Jayanta K.,Willis, Anthony C.
experimental part, p. 9252 - 9262 (2011/01/12)
The Pd[0]-catalyzed Ullmann cross-coupling of o-nitrohaloarenes 1a-e with the brominated heterocycles 2a-f delivers the expected products 3a-j in good to excellent yields. The reductive cyclization of such products, as well as N-acyl derivatives 3k, l, and m, has been investigated and provided the C-3 mono-substituted oxindoles 5a-d, f, g, k, and m, the direct reduction products 4i and j or indole 5l.
Geldanamycin derivative inhibition of HGF/SF-mediated Met tyrosine kinase receptor-dependent urokinase-plasminogen activation
Shen, Yuehai,Xie, Qian,Norberg, Monica,Sausville, Edward,Vande Woude, George,Wenkert, David
, p. 4960 - 4971 (2007/10/03)
Ansamycins, including geldanamycin and the derivative 17-allylamino-17- demethoxygeldanamycin, and radicicol are known for their ability to tightly bind to the ATP-binding site of the amino-terminal domain region of heat shock protein 90. We have found that geldanamycin and some of its derivatives can inhibit hepatocyte growth factor/scatter factor-mediated Met tyrosine kinase receptor-dependent urokinase-plasminogen activation at femtomolar levels. Assessment is made of structural requirements for such an activity and evidence is given that distinguishes the target of such an activity from that of heat shock protein 90.
GELDANAMYCIN AND DERIVATIVES INHIBIT CANCER INVASION AND IDENTIFY NOVEL TARGETS
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Page/Page column 41, (2008/06/13)
Geldanamycin derivatives that block the uPA-plasmin network and inhibit growth and invasion by glioblastoma cells and other tumors at femtomolar concentrations are potentially highly active anti-cancer drugs. GA and various 17-amino-17-demethoxygelddanamycin derivatives are disclosed that block HGF/SF-mediated Met tyrosine kinase receptor-dependent uPA activation at fM levels. Other ansamycins (macbecins I and II), GA derivatives, and radicicol required concentrations several logs higher (≥nM) to achieve such inhibition. The inhibitory activity of tested compounds was discordant with the known ability of drugs of this class to bind to hsp90, indicating the existence of a novel target(s) for HGF/SF -mediated events in tumor development. Methods of using such compounds to inhibit cancer cell activities and to treat tumors are disclosed. Such treatment with low doses of these highly active compounds provide an option for treating various Met-expressing tumors, in particular invasive brain cancers, either alone or in combination with conventional surgery, chemotherapy, or radiotherapy.
