1070705-45-1Relevant 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 (2018/05/29)
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.
Synthesis of new oxazolidinonyl/oxazolidinyl carbazole derivatives for ss-blocking activity
Anumula, Raghupathi Reddy,Kagga, Mukkanti,Ghanta, Mahesh Reddy,Padi, Pratap Reddy
, p. 315 - 322 (2008/03/13)
Preparation of some new carbazolyloxy propanolamine derivatives and their cyclization into corresponding oxazolidinonyl/oxazolidinyl carbazole derivatives were described.
