345264-15-5Relevant articles and documents
Development of Bisindole-Substituted Aminopyrazoles as Novel GSK-3β Inhibitors with Suppressive Effects against Microglial Inflammation and Oxidative Neurotoxicity
Liu, Jian-Guo,Zhao, Danfeng,Gong, Qi,Bao, Fengxia,Chen, Wen-Wen,Zhang, Haiyan,Xu, Ming-Hua
, p. 3398 - 3408 (2020/11/26)
Development of glycogen synthase kinase-3β (GSK-3β) inactivation-centric agents with polypharmacological profiles is increasingly recognized as a promising therapeutic strategy against the multifactorial etiopathology of Alzheimer's disease (AD). In this respect, a series of disubstituted aminopyrazole derivatives were designed and synthesized as a new class of GSK-3β inhibitors. Most of these derivatives possess GSK-3β inhibitory activities with IC50 values in the micromolar ranges, among which bisindole-substituted aminopyrazole derivative 6h displayed moderate GSK-3β inhibition (IC50 = 1.76 ± 0.19 μM), and alleviative effects against lipopolysaccharide (LPS)-induced glial inflammation in BV-2 cells and glutamate-induced oxidative neurotoxicity in HT-22 cells. Further in vivo studies indicated that compound 6h had potent anti-inflammatory effect, by showing markedly reduced microglial activation and astrocyte proliferation in the brain of LPS-injected mice. Overall, the simultaneous modulation of 6h on multiple dysfunctions of disease network highlights this structural distinctively bisindole-substituted aminopyrazole could be a useful prototype for the discovery of novel therapeutic agents to tackle AD and other GSK-3β associated complex neurological syndromes.
HDAC INHIBITORS
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Page/Page column 57; 59-60, (2009/04/25)
The present invention provides hydroxamic acid compounds, and methods of preparation of these compounds. The present invention also relates to pharmaceutical compositions comprising the hydroxamic acid compounds. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a compound of the present invention.
Preparation of novel aza-1,7-annulated indoles and their conversion to potent indolocarbazole kinase inhibitors
Al-awar, Rima S.,Ray, James E.,Hecker, Kyle A.,Joseph, Sajan,Huang, Jianping,Shih, Chuan,Brooks, Harold B.,Spencer, Charles D.,Watkins, Scott A.,Schultz, Richard M.,Considine, Eileen L.,Faul, Margaret M.,Sullivan, Kevin A.,Kolis, Stanley P.,Carr, Michael A.,Zhang, Faming
, p. 3925 - 3928 (2007/10/03)
The synthesis of novel aza-1,7-annulated indoles was achieved and these were converted to indolocarbazoles that proved to be potent kinase inhibitors. These compounds were also evaluated in a human colon carcinoma cell line and proved to be good antiproliferative agents.
