90004-94-7Relevant academic research and scientific papers
PRMT5 INHIBITORS
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Page/Page column 113-114, (2021/06/26)
The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.
Immunoproteasome Inhibitor-Doxorubicin Conjugates Target Multiple Myeloma Cells and Release Doxorubicin upon Low-Dose Photon Irradiation
Dekker, Patrick M.,Florea, Bogdan I.,Maiorana, Santina,Maurits, Elmer,Neefjes, Jacques J. C.,Overkleeft, Herman S.,Van De Graaff, Michel J.,Van Der Zanden, Sabina Y.,Van Kasteren, Sander I.,Wander, Dennis P. A.
supporting information, p. 7250 - 7253 (2020/08/06)
Proteasome inhibitors are established therapeutic agents for the treatment of hematological cancers, as are anthracyclines such as doxorubicin. We here present a new drug targeting approach that combines both drug classes into a single molecule. Doxorubicin was conjugated to an immunoproteasome-selective inhibitor via light-cleavable linkers, yielding peptide epoxyketone-doxorubicin prodrugs that remained selective and active toward immunoproteasomes. Upon cellular uptake and immunoproteasome inhibition, doxorubicin is released from the immunoproteasome inhibitor through photoirradiation. Multiple myeloma cells in this way take a double hit: immunoproteasome inhibition and doxorubicin-induced toxicity. Our strategy, which entails targeting of a cytotoxic agent, through a covalent enzyme inhibitor that is detrimental to tumor tissue in its own right, may find use in the search for improved anticancer drugs.
Palladium-catalyzed chelation-assisted aromatic C-H nitration: Regiospecific synthesis of nitroarenes free from the effect of the orientation rules
Zhang, Wei,Lou, Shaojie,Liu, Yunkui,Xu, Zhenyuan
, p. 5932 - 5948 (2013/07/26)
A palladium-catalyzed chelation-assisted ortho-nitration of aryl C-H bond is described. A range of azaarenes such as 2-arylquinoxalines, pyridines, quinoline, and pyrazoles were nitrated with excellent chemo- and regioselectivity. Using the O-methyl oximyl group as a removable directing group, the regiospecific synthesis of a variety of o-nitro aryl ketones was achieved starting from aryl ketones via a three-step process involving the Pd-catalyzed ipso-nitration of C-H bond as a key step. Mechanistic investigations support a silver-mediated radical mechanism involving Pd((II/III) and/or Pd(II/IV) catalytic cycles under oxidizing conditions.
INHIBITORS OF LRRK2 KINASE ACTIVITY
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Page/Page column 152, (2012/12/13)
The present invention provides compounds having a structure according to Formula I: (I) or a salt or solvate thereof, wherein R1, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.
Regiospecific synthesis of nitroarenes by palladium-catalyzed nitrogen-donor-directed aromatic C-H nitration
Liu, Yun-Kui,Lou, Shao-Jie,Xu, Dan-Qian,Xu, Zhen-Yuan
supporting information; experimental part, p. 13590 - 13593 (2011/03/18)
Nitration of N-heteroaromatics: The first example of palladium-catalyzed direct ortho-nitration of aryl C-H bonds is described. A range of azaarenes, such as 2-arylquinoxalines, pyridines, pyrazoles, and O-methyl oximes, were nitrated with excellent chemo- and regioselectivity (see scheme; DCE=1,2-dichloroethane). Preliminary mechanistic investigations support a silver-mediated radical mechanism involving palladium(II/III) and/or palladium(II/IV) catalytic cycles under oxidizing conditions. Copyright
