- Synthesis and Target Identification of Benzoxepane Derivatives as Potential Anti-Neuroinflammatory Agents for Ischemic Stroke
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Benzoxepane derivatives were designed and synthesized, and one hit compound emerged as being effective in vitro with low toxicity. In vivo, this hit compound ameliorated both sickness behavior through anti-inflammation in LPS-induced neuroinflammatory mice model and cerebral ischemic injury through anti-neuroinflammation in rats subjected to transient middle cerebral artery occlusion. Target fishing for the hit compound using photoaffinity probes led to identification of PKM2 as the target protein responsible for anti-inflammatory effect of the hit compound. Furthermore, the hit exhibited an anti-neuroinflammatory effect in vitro and in vivo by inhibiting PKM2-mediated glycolysis and NLRP3 activation, indicating PKM2 as a novel target for neuroinflammation and its related brain disorders. This hit compound has a better safety profile compared to shikonin, a reported PKM2 inhibitor, identifying it as a lead compound in targeting PKM2 for the treatment of inflammation-related diseases.
- Gao, Cheng-Long,Hou, Gui-Ge,Liu, Jin,Ru, Tong,Xu, Ya-Zhou,Zhao, Shun-Yi,Ye, Hui,Zhang, Lu-Yong,Chen, Kai-Xian,Guo, Yue-Wei,Pang, Tao,Li, Xu-Wen
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- Benzoxepine-5-ketone compound as well as preparation method and application thereof
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The invention relates to a benzoxazepine-5-ketone compound as well as a preparation method and application thereof. The benzoxazepine-5-ketone compound has a structure as shown in a formula (I) defined in the description. The benzoxazepine-5-ketone compound can block the excessive generation of pro-inflammatory factors in the brain, and provides a feasible alternative treatment strategy for treating AIS.
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- Polycyclic thiazolidin-2-ylidene amines, process for their preparation, and their use as pharmaceuticals
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Polycyclic thiazolidin-2-ylidene amines and their physiologically tolerable salts and physiologically functional derivatives of the formula I in which the radicals have the meanings indicated, and their physiologically tolerable salts and a process for their preparation are described. The compounds are suitable, for example, as anorectics.
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- 2,3,4,5-tetrahydro-1-benzoxepins, the use thereof and pharmaceutical products based on these compounds
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2,3,4,5-Tetrahydro-1-benzoxepins of the formula I STR1 with R1 equaling, inter alia, H, alkyl, alkoxy, Hal, alkylsulfonyl, arylsulfonyl, R2 equaling H, alkyl, alkoxy, OH, R3 to R6 H or alkyl and X equaling STR2 have excellent efficacy as antihypertensives, as coronary therapeutics, as agents for the treatment of cardiac insufficiency, of disturbances of cerebral and peripheral blood flow or of disturbances of intestinal motility, premature labor, obstructions of the airways or of the urinary tract or of the biliary tract or as spasmolytics.
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- Conformational and Steric Modifications of the Pyran Ring of the Potassium-Channel Activator Cromakalim
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The syntheses of analogues of the novel smooth muscle relaxant cromakalim, in which the C-2 methyl groups have been successively replaced by hydrogen, are described and the relative stereochemistry of the two corresponding, isomeric monomethyl compounds,
- Buckle, Derek R.,Eggleston, Drake S.,Houge-Frydrych, Catherina S. V.,Pinto, Ivan L.,Readshaw, Simon A.,et al.
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p. 2763 - 2772
(2007/10/02)
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