- Compounds & Methods for the Enhanced Degradation of Targeted Proteins & Other Polypeptides by an E3 Ubiquitin Ligase
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The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins that are degraded and/or otherwise inhibited by bifunctional compounds of the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand that binds to the ubiquitin ligase and on the other end a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds of the present invention, consistent with the degradation/inhibition of targeted polypeptides.
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Paragraph 0427
(2014/12/09)
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- Dynamic mirror-symmetry breaking in bicontinuous cubic phases
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Chiral segregation of enantiomers or chiral conformers of achiral molecules during self-assembly in well-ordered crystalline superstructures has fascinated chemists since Pasteur. Here we report spontaneous mirror-symmetry breaking in cubic phases formed
- Dressel, Christian,Liu, Feng,Prehm, Marko,Zeng, Xiangbing,Ungar, Goran,Tschierske, Carsten
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supporting information
p. 13115 - 13120
(2015/01/16)
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- Small-Molecule Choline Kinase Inhibitors as Anti-Cancer Therapeutics
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Small molecule choline kinase inhibitors having the following formula: are provided herein. Also provided herein are pharmaceutical compositions containing Formula I compounds, together with methods of treating cancer, methods of inhibiting choline kinase enzymatic activity, and methods of treating tumors by administering an effective amount of a Formula I compound.
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Page/Page column 20; 27-28
(2011/10/31)
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- Enantiodifferentiating photoisomerization of cyclooctene included and sensitized by benzoate modified β-cyclodextrin derivatives: Switching of product chirality by solvent
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Solvent effect upon asymmetric photosensitization has been investigated in the enantiodifferentiating photoisomerization of cyclooctene(1Z), sensitized by benzoate modified β-cyclodextrin derivatives bearing nitrogen, oxygen or sulfur substituents. The enantiomeric excess (ee) and E/Z ratio of reaction products were susceptible to the concentration of methanol in the aqueous solution, which could switch to the chirality of product unprecedentedly. Further investigation indicated that the conformation of the modified CDs in aqueous methanol solutions with 1Z were highly sensitive to both the substituent(s) on benzoate moiety of the modified CDs and the concentration of methanol. Solvent content represents a new versatile tool to efficiently manipulate the asymmetric photochemical reactions, in which the chirality of products can be switched by simply changing the methanol content of reaction solvent rather than synthesizing the antipodal sensitizers.
- Li, Guangxun,Wang, Zhizhong,Lu, Runhua,Tang, Zhuo
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scheme or table
p. 3097 - 3101
(2011/06/26)
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- Synthesis, gastrointestinal prokinetic activity and structure-activity relationships of novel N-[[2-(dialkylamino)ethoxy]benzyl]benzamide derivatives
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Novel N-[[2-(dialkylamino)ethoxy]benzyl]benzamide derivatives (II-1-51), derived from the structural modification of metoclopramide (1), were synthesized and examined for their pharmacological activities. Among them, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide (II-34) which exhibited well balanced gastrointestinal prokinetic and antiemetic activities was selected as a new type of gastrointestinal prokinetic agent.
- Sakaguchi,Nishino,Ogawa,Iwanaga,Yasuda,Kato,Ito
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p. 202 - 211
(2007/10/02)
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