- COMPOUNDS AND USES THEREOF
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The present invention features compounds useful in the treatment of neurological disorders and primary brain cancer. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders and primary brain cancer.
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Page/Page column 236
(2020/10/20)
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- As neuroprotective agents of pharmaceutical compounds
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The invention discloses a medicinal compound as a neuroprotective agent. The medicinal compound is a neuronal nitric oxide synthase-postsynaptic density protein 95 (nNOS-PSD95) decoupling agent. The medicinal compound is a benzene ring derivative shown in the general formula (I) or its pharmaceutically acceptable salt. The invention further discloses a preparation method of the medicinal compound and a use of the medicinal compound in prevention and treatment on neuronal damage influence-caused diseases.
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Paragraph 0299; 0300; 0307; 0308
(2019/06/26)
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- COMPOUNDS AND USES THEREOF
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The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
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Page/Page column 229
(2019/10/15)
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- HDAC3-SELECTIVE INHIBITORS
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Disclosed herein are selective HDAC inhibitors. In some embodiments, the compounds are selective HDAC3 inhibitors. The compounds are useful to treat a variety of conditions, including cancers, i.e., breast cancer, cachexia, and liver steatosis.
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Page/Page column 27-28
(2019/01/05)
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- Targeting breast cancer stem cells by novel HDAC3-selective inhibitors
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Although histone deacetylase (HDAC) inhibitors have been known to suppress the cancer stem cell (CSC) population in multiple types of cancer cells, it remains unclear which HDAC isoforms and corresponding mechanisms contribute to this anti-CSC activity. Pursuant to our previous finding that HDAC8 regulates CSCs in triple-negative breast cancer (TNBC) cells by targeting Notch1 stability, we investigated related pathways and found HDAC3 to be mechanistically linked to CSC homeostasis by increasing β-catenin expression through the Akt/GSK3β pathway. Accordingly, we used a pan-HDAC inhibitor, AR-42 (1), as a scaffold to develop HDAC3-selective inhibitors, obtaining the proof-of-concept with 18 and 28. These two derivatives exhibited high potency and isoform selectivity in HDAC3 inhibition. Equally important, they showed in vitro and/or in vivo efficacy in suppressing the CSC subpopulation of TNBC cells via the downregulation of β-catenin.
- Hsieh, Hao-Yu,Chuang, Hsiao-Ching,Shen, Fang-Hsiu,Detroja, Kinjal,Hsin, Ling-Wei,Chen, Ching-Shih
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supporting information
p. 42 - 51
(2017/09/20)
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- PROBES FOR IMAGING HUNTINGTIN PROTEIN
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Provided are imaging agents comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and methods of their use.
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Paragraph 0345
(2016/03/22)
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- PYRROLO[2,3-D]PYRIMIDINYL, PYRROLO[2,3-B]PYRAZINYL AND PYR-ROLO[2,3-D]PYRIDINYL ACRYLAMIDES
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The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.
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Paragraph 0292
(2015/06/17)
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- Discovery of Potent, orally bioavailable phthalazinone bradykinin B1 receptor antagonists
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The bradykinin B1 receptor is rapidly induced upon tissue injury and inflammation, stimulating the production of inflammatory mediators resulting in plasma extravasation, leukocyte trafficking, edema, and pain. We have previously reported on sulfonamide and sulfone-based B1 antagonists containing a privileged bicyclic amine moiety leading to potent series of 2-oxopiperazines. The suboptimal pharmacokinetics and physicochemical properties of the oxopiperazine sulfonamides led us to seek B1 antagonists with improved druglike properties. Using a pharmacophore model containing a bicyclic amine as anchor, we designed a series of amide antagonists with targeted physicochemical properties. This approach led to a novel series of potent phthalazinone B1 antagonists, where we successfully replaced a sulfonamide acceptor with a cyclic carbonyl unit. SAR studies revealed compounds with subnanomolar B1 binding affinity. These compounds demonstrate excellent cross-species PK properties with high oral bioavailability and potent activity in a rabbit biochemical challenge pharmacodynamic study.
- Biswas, Kaustav,Peterkin, Tanya A. N.,Bryan, Marian C.,Arik, Leyla,Lehto, Sonya G.,Sun, Hong,Hsieh, Feng-Yin,Xu, Cen,Fremeau, Robert T.,Allen, Jennifer R.
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experimental part
p. 7232 - 7246
(2012/01/03)
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- THERAPEUTIC ARYL-AM I DO-ARYL COMPOUNDS AND THEIR USE
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The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-amido-aryl compounds of the following formula (for convenience, collectively referred to herein as "AAA compounds"), which, inter alia, a
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Page/Page column 92-93
(2011/04/14)
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- Synthesis and antiproliferative activity of pyrrolo[3,2-b]pyridine derivatives against melanoma
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Synthesis of a new series of diarylureas and amides having pyrrolo[3,2-b]pyridine scaffold is described. Their in vitro antiproliferative activity against human melanoma cell line A375 and HS 27 human fibroblast cell line was tested and the effect of subs
- Kim, Hee Jin,Jung, Myung-Ho,Kim, Hwan,El-Gamal, Mohammed I.,Sim, Tae Bo,Lee, So Ha,Hong, Jun Hee,Hah, Jung-Mi,Cho, Jung-Hyuck,Choi, Jung Hoon,Yoo, Kyung Ho,Oh, Chang-Hyun
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scheme or table
p. 413 - 417
(2010/03/25)
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- Discovery of inhibitors of aberrant gene transcription from libraries ofdna binding molecules: Inhibition of LEF-1-mediated gene transcription and oncogenic transformation
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The screening of a >9000 compound library of synthetic DNA binding molecules for selective binding to the consensus sequence of the transcription factor LEF-1 followed by assessment of the candidate compounds in a series of assays that characterized functional activity (disruption of DNA-LEF-1 binding) at the intended target and site (inhibition of intracellular LEF-1-mediated gene transcription) resulting in a desired phenotypic cellular change (inhibit LEF-1-driven cell transformation) provided two lead compounds: lefmycin-1 and lefmycin-2. The sequence of screens defining the approach assures that activity in the final functional assay may be directly related to the inhibition of gene transcription and DNA binding properties of the identified molecules. Central to the implementation of this generalized approach to the discovery of DNA binding small molecule inhibitors of gene transcription was (1) the use of a technically nondemanding fluorescent intercalator displacement (FID) assay for initial assessment of the DNA binding affinity and selectivity of a library of compounds for any sequence of interest, and (2) the technology usedto prepare a sufficiently large library of DNA binding compounds.
- Stover, James S.,Shi, Jin,Jin, Wei,Vogt, Peter K.,Boger, Dale L.
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supporting information; experimental part
p. 3342 - 3348
(2009/07/30)
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- 2-HETEROARYLAMINO-PYRIMIDINE DERIVATIVES AS KINASE INHIBITORS
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The invention provides compounds of Formula (I) and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or der
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Page/Page column 43
(2009/04/25)
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- AZAINDOLE DERIVATIVES AS INHIBITORS OF P38 KINASE
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The invention is directed to methods to inhibit p38 kinase, preferably p38-α using compounds which are azaindoles wherein the azaindoles are coupled through an azacyclic linker to another cyclic moiety.
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- EFFECT OF SUBSTITUENTS ON CHEMICAL SHIFT OF PROTONS OF THE AMINO GROUP IN PMR SPECTRA OF SUBSTITUTED AMINOPYRIDINES
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The effect of substituents on the chemical shift of the protons of the amino group in six series of m- and p-substituted 2-, 3- and 4-aminopyridines (in DMSO) was studied by correlation analysis using the inductive and resonance constants.The peculiarities of the pyridine ring in the transmission of the electronic effects of the substituents are discussed.
- Shkurko, O. P.,Mamaev, V. P.
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- 2-(2-imidazolin-2-yl)-pyridines and quinolines, process and intermediates for the preparation thereof, and use of said compounds as herbicidal agents
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There are provided novel 2-(2-imidazolin-2-yl)pyridine and quinoline compounds, a process and intermediate compounds for the preparation thereof, and a method for controlling a wide variety of annual and perennial plant species therewith.
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