- Toll-like receptor-7 small molecule inhibitor and preparation method thereof
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The invention belongs to the field of chemical small molecules, and particularly relates to a Toll-like receptor-7 small molecule inhibitor. The invention provides the Toll-like receptor-7 small molecule inhibitor, which takes a co-inhibitor of TLR7 and TLR8 obtained by screening as a research object, realizes selective regulation and control of TLR7 and TLR8 through the research on the structureoptimization and structure-activity relationship (SAR) of a parent compound, and further develops a high-efficiency, non-toxic and specific small molecule inhibitor with certain selectivity on TLR 7.The TLR7 small molecule inhibitor has a certain effect and potential medicinal value in autoimmune diseases (systemic lupus erythematosus).
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Paragraph 0040-0043
(2021/02/24)
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- Metal-Binding Pharmacophore Library Yields the Discovery of a Glyoxalase 1 Inhibitor
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Anxiety and depression are common, highly comorbid psychiatric diseases that account for a large proportion of worldwide medical disability. Glyoxalase 1 (GLO1) has been identified as a possible target for the treatment of anxiety and depression. GLO1 is a Zn2+-dependent enzyme that isomerizes a hemithioacetal, formed from glutathione and methylglyoxal, to a lactic acid thioester. To develop active inhibitors of GLO1, fragment-based drug discovery was used to identify fragments that could serve as core scaffolds for lead development. After screening a focused library of metal-binding pharmacophores, 8-(methylsulfonylamino)quinoline (8-MSQ) was identified as a hit. Through computational modeling and synthetic elaboration, a potent GLO1 inhibitor was developed with a novel sulfonamide core pharmacophore. A lead compound was demonstrated to penetrate the blood-brain barrier, elevate levels of methylglyoxal in the brain, and reduce depression-like behavior in mice. These findings provide the basis for GLO1 inhibitors to treat depression and related psychiatric illnesses.
- Perez, Christian,Barkley-Levenson, Amanda M.,Dick, Benjamin L.,Glatt, Peter F.,Martinez, Yadira,Siegel, Dionicio,Momper, Jeremiah D.,Palmer, Abraham A.,Cohen, Seth M.
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p. 1609 - 1625
(2019/02/14)
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- Novel Sulfonaminoquinoline Hepcidin Antagonists
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The present invention relates to novel hepcidin antagonists, pharmaceutical compositions comprising them and the use thereof as medicaments for the use in the treatment of iron metabolism disorders, such as, in particular, iron deficiency diseases and anemias, in particular anemias in connection with chronic inflammatory diseases.
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Page/Page column 173
(2012/09/05)
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