- Optimization and biological evaluation of 2-aminobenzothiazole derivatives as Aurora B kinase inhibitors
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A strong relationship between abnormal functions of Aurora kinases and tumorigenesis has been reported for decades. Consequently, Aurora kinases serve as potential targets for anticancer agents. Here, we identified aminobenzothiazole derivatives as novel inhibitors of Aurora B kinase through bioisosteric replacement of the previous inhibitors, aminobenzoxazole derivatives. Most of the urea-linked aminobenzothiazole derivatives showed potent and selective inhibitory activity against Aurora B kinase over Aurora A kinase. Molecular modeling indicated that compound 15g bound well to the active site of Aurora B kinase and formed the essential hydrogen bonds. The potent compounds, 15g and 15k, were selected, and their biological effects were evaluated using HeLa cell lines. It was found that these compounds inhibited the phosphorylation of histone H3 at Ser10 and induced G2/M cell cycle arrest. We suggest that the reported compounds have the potential to be further developed as anticancer therapeutics.
- Lee, Eun,An, Ying,Kwon, Junhee,Kim, Keun Il,Jeon, Raok
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p. 3614 - 3622
(2017/06/13)
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- SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
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The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 968
(2018/01/20)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Paragraph 0175
(2014/05/24)
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- Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
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This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.
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- Indole, azaindole and related heterocyclic 4-alkenyl piperidine amides
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This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with new piperidine 4-alkenyl derivatives that possess unique antiviral activity. More particularly, the present invention relates to compounds useful for the treatment of HIV and AIDS. The compounds of the invention for the general Formula I: wherein: Z is Q is selected from the group consisting of: —W— is
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Page/Page column 90
(2010/02/06)
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- Synthesis of Macrobicyclic Ligands containing Pyrazole Subunits: the N,N'-Bipyrazolyl Cryptand
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The pyrazolyl cryptands (1) and (2) have been obtained in one-step, non high-dilution macrobicyclization reaction, from a 1,1'-bipyrazole derivative; similarly, tripodal ligands (7)-(9) with pyrazole structures are described.
- Juanes, Olga,Mendoza, Javier de,Rodriguez-Ubis, Juan-Carlos
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p. 1765 - 1766
(2007/10/02)
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- Mass Spectrometry of Nitroazoles. 3-Ortho Effects: The loss of OH. and H2O from Methyl Substituted Nitrodiazoles
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Methyl substituted nitrodiazoles which have the substituents at adjacent positions in the ring are subject to several ortho effects.Deuterium labelling of the methyl group and the mobile N-bonded hydrogen show that the loss of OH. originates from the substituents.In some cases the N-bonded hydrogen atom participates also in the loss of OH. and of H2O.
- Luijten, W. C. M. M.,Thuijl, J. van
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p. 299 - 303
(2007/10/02)
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