- Development of Noviomimetics as C-Terminal Hsp90 Inhibitors
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KU-32 and KU-596 are novobiocin-derived, C-terminal heat shock protein 90 (Hsp90) modulators that induce Hsp70 levels and manifest neuroprotective activity. However, the synthetically complex noviose sugar requires 10 steps to prepare, which makes translational development difficult. In this study, we developed a series of "noviomimetic" analogues of KU-596, which contain noviose surrogates that can be easily prepared, while maintaining the ability to induce Hsp70 levels. Both sugar and sugar analogues were designed, synthesized, and evaluated in a luciferase reporter assay, which identified compound 37, a benzyl containing noviomimetic, as the most potent inducer of Hsp70.
- Anyika, Mercy,McMullen, Mason,Forsberg, Leah K.,Dobrowsky, Rick T.,Blagg, Brian S. J.
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- SULFONIUM COMPOUND, ACID GENERATOR, CURABLE COMPOSITION, AND CURED PRODUCT
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PROBLEM TO BE SOLVED: To provide a novel sulfonium compound that can be used for an acid generator to generate an acid in response to heating or irradiation with an energy ray. SOLUTION: There is provided a sulfonium compound represented by the general fo
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Paragraph 0065-0069
(2021/05/21)
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- MERTK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00946
(2020/01/31)
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- SULFONYL-SUBSTITUTED BICYCLIC COMPOUND WHICH ACTS AS ROR INHIBITOR
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Provided is a sulfonyl-substituted bicyclic compound (A) which acts as a RORγ inhibitor, said compound has good RORγ inhibitory activity and is expected to be used for treating diseases mediated by a RORγ receptor in mammals.
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Paragraph 0603; 0604
(2020/08/16)
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- NOVEL COMPOUND For Organic light emitting diode AND COATING COMPOSITION FOR ORGANIC LAYER COMPRISING THE SAME
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Provided are a compound represented by chemical formula (1) and a coating liquid composition comprising the same. The above formula (1) is as described in the description of the invention.
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Paragraph 0137; 0138; 0139; 0140; 0201; 0202; 0203; 0204
(2020/12/29)
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 2522; 2523
(2019/07/10)
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- Development of noviomimetics that modulate molecular chaperones and manifest neuroprotective effects
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Heat shock protein 90 (Hsp90) is a chaperone under investigation for the treatment of cancer and neurodegenerative diseases. Neuroprotective Hsp90 C-terminal inhibitors derived from novobiocin (novologues) include KU-32 and KU-596. These novologues modulate molecular chaperones and result in an induction of Heat Shock Protein 70 (Hsp70). “Noviomimetics” replace the synthetically complex noviose sugar with a simple cyclohexyl moiety to maintain biological efficacy as compared to novologues KU-596 and KU-32. In this study, we further explore the development of noviomimetics and evaluate their efficacy using a luciferase refolding assay, immunoblot analysis, a c-jun assay, and an assay measuring mitochondrial bioenergetics. These new noviomimetics were designed and synthesized and found to induce Hsp70 and improve biological activity. Noviomimetics 39e and 40a were found to induce Hsp70 and exhibit promising effects in cellular assays.
- Forsberg, Leah K.,Anyika, Mercy,You, Zhenyuan,Emery, Sean,McMullen, Mason,Dobrowsky, Rick T.,Blagg, Brian S.J.
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p. 1428 - 1435
(2017/11/17)
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- BIPHENYL AMIDES WITH MODIFIED ETHER GROUPS AS HSP90 INHIBITORS AND HSP70 INDUCERS
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Provided herein are compounds of the formulas: (I) wherein: n, X2, R3, R3', R4, R4', R5, R5', R6, and R6' are as defined herein. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including diabetic peripheral neuropathy or cancer.
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Page/Page column 70
(2016/04/19)
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- C-TERMINAL HSP90 INHIBITORS
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Hsp90 C-terminal inhibitors and pharmaceutical compositions containing such compounds are provided. The compounds of the disclosure are useful for the treatment and/or prevention of neurodegenerative disorders such as diabetic peripheral neuropathy.
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Paragraph 00327; 00328; 00329
(2013/08/28)
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- Heterocylic antiviral compounds
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This invention relates to piperidine derivatives of formula I wherein R1, R2, R3 and R4 are as defined herein useful in the treatment of a variety of disorders, including those in which the modulation of CCR5 re
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Page/Page column 30
(2008/12/08)
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- MICROWAVE ROTATIONAL SPECTRUM, ELECTRIC DIPOLE MOMENT AND GEOMTRY OF 2-BICYCLOHEXANONE
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We report the microwave rotational spectrum of 2-bicyclohexanone in its vibrational ground state and in vibrationally excited states associared with the bending mode νB of the five-membered ring.Variation of the rotational constants with vb allows the conclusion that five/membered ring is effectively planar although the mode vb is governed by an asssymetric potential energy function.Measurement of the Stark effect in a number of transitions leads to the components μa=3.28+/-0.02D and μb=1.81+/-0.2D of the electric dipole moment.
- Davies, Ann P.,Legon, A. C.,Millen, D. J.,Roberts, A. J.
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