- 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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supporting information
p. 2429 - 2439
(2020/01/03)
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- Acid-labile anchor groups for the synthesis of peptide amides by a solid-phase method
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The invention relates to new compounds of the formula STR1 in which R1 denotes (C1 -C8)-alkyl, R2 denotes an amino acid residue which is protected with a urethane protective group which can be eliminated with weak acid or base, or denotes an amino protective group which can be eliminated with weak acid or base, R3 denotes hydrogen or (C1 -C4)-alkyl, and Y1 -Y9 denote identical or different radicals hydrogen, (C1 -C4)-alkyl, (C1 -C4)-alkoxy or --O--(CH2)n --COOH (with n=1 to 6), with one of these radicals being --O--(CH2)n --COOH, or Y1, Y2 and Y5 -Y9 denote identical or different radicals hydrogen, (C1 -C4)-alkyl or (C1 -C4)-alkoxy, Y3 denotes hydrogen or (C1 -C8)-alkoxy and Y4 denotes --(CH2)n --COOH or --NH--CO--(CH2)n --COOH (with n=1 to 6). Processes for the preparation thereof and the synthesis of peptide amides by a solid-phase method using these new compounds (spacers) are described.
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- Selective Mono- and Bis(alkoxycarbonylation)s of Olefins Catalyzed by Palladium in the Presence of Cu(I) or Cu(II) Chloride under Remarkably Mild Conditions. Application to the Synthesis of γ-Butyrolactone Derivatives
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Palladium-catalyzed mono- and bis(alkoxycarbonylation)s of the olefins were controlled by the use of copper(II) and copper(I) chloride, respectively, in alcohol under normal pressure of carbon monoxide and oxygen at room temperature without any other additives. 3-Buten-1-ols gave the corresponding γ-butyrolactones and 2-oxotetrahydrofuran-3-acetic acid esters, respectively, in high yields.
- Toda, Shiho,Miyamoto, Masanori,Kinoshita, Hideki,Inomata, Katsuhiko
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p. 3600 - 3606
(2007/10/02)
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- Liquid Crystalline Properties of Cholesteryl ω-Arylalkanoates
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The thermal properties of the homologous series of cholesteryl ω-(4-benzoylphenyl)- (I), ω-(4-benzylphenyl)- (II), ω-benzoyl- (III), and ω-phenoxyalkanoate (IV) have been investigated.For series I and II the cholesteric-isotropic (Ch-I) transition temperatures, enthalpies, and entropies show a remarkable alternation.For series III and IV, the transition temperatures, enthalpies, and entropies exhibit weak alternation and their trends are opposite to those for series I and II, and the cholesteryl ω-phenylalkanoates.The cholesteric-isotropic transition temperatures are discussed in terms of the geometrical and electrical alternations stemming from the terminal aryl groups, and also the relative importance between these two terms.
- Koden, Mitsuhiro,Miyake, Shiro,Takenaka, Shunsuke,Kusabayashi, Shigekazu
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p. 2387 - 2390
(2007/10/02)
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