908228-44-4Relevant articles and documents
Discovery of novel small molecule TLR4 inhibitors as potent anti-inflammatory agents
Xu, Yao,Chen, Shujun,Cao, Ying,Zhou, Pingzheng,Chen, Zhipeng,Cheng, Kui
, p. 253 - 266 (2018)
Toll-like receptor 4 (TLR4) initiates innate immune response to release inflammatory cytokines and has been pathologically linked to variety of inflammatory diseases. Recently, we found that Carvedilol, as the classic anti-heart failure and anti-inflammatory clinic drug, could inhibit the TLR4 signaling in the TLR4 overexpressed cells. Herein, we have designed and synthesized a small library of novel Carvedilol derivatives and investigated their potential inhibitory activity. The results indicate that the most potent compound 8a (SMU-XY3) could effectively inhibited TLR4 protein and the LPS triggered alkaline phosphatase signaling in HEK-Blue hTLR4 cells. It down regulated the nitric oxide (NO) in both RAW264.7 cells and BV-2 microglial cells, in addition to blocking the TNF-α signaling in ex-vivo human peripheral blood mononuclear cells (PBMC). More interestingly, 8a shows higher affinity to hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) over HCN2, which probably indicates the new application of TLR4 inhibitor 8a in heart failure, coronary heart disease, and other inflammatory diseases.
Substituted phenol beta-amino alcohol derivatives and production method and application thereof
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Paragraph 0051; 0057-0058, (2019/07/10)
The invention relates to substituted phenol beta-amino alcohol derivatives. Structures of the substituted phenol beta-amino alcohol derivatives are as shown in the description, wherein R1 is substituted halogen atoms, amidogen, nitro, C1-6 alkyl, C1-6 alk
TOLL-LIKE RECEPTOR MODULATORS AND USES THEREOF
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Page/Page column 28; 31, (2011/04/24)
The present invention provides a compound selected from the group consisting of: Formula (I) and Formula (II), where n, m, X1, X2, X3, X4, R1, R2, R3, R11, R12/s